Nano-Tera.ch 1Nano-Tera.ch 1

Prof. Giovanni De Micheli Nano-Tera.ch Program Leader,Executive Committee Chair

NaNo-TEra.Ch: fuNDiNG rEsEarCh iN sysTEMs ENGiNEEriNG

Nano-Tera.ch is a national funding program supporting research in engineering of complex (tera-scale) systems for health, security and the environment using nanotechnologies. Recent emphasis has also been placed on energy, a central theme affecting system design, society and the economy. Nano-Tera.ch research funding is open to all Swiss institutions according to the corresponding legislation. Morever, Nano-Tera.ch fosters collaboration among researchers and industries that are partners or supporters of the research projects.

The Swiss National Science Foundation (SNSF) contributes to the Nano-Tera.ch program by evaluating and monitoring the large research projects through an international panel of experts, thus ensuring the high scientific quality of the program.

The mission of Nano-Tera.ch includes research, development and technology transfer as well as education and dissemination. The final objective is to enable mechanisms that can map the high productivity of research ideas, publications and patents of the Swiss community into a significant momentum in terms of industrial growth as well as job and enterprise creation. This specific engineering focus differentiates Nano-Tera.ch from other funding programs.

Prof. heinrich Meyr,Nano-Tera.ch Scientific Advisory Board Chair

NaNo-TEra.Ch: swiss ExCELLENCE iN rEsEarCh

The Scientific Advisory Board reviews the Nano-Tera.ch program as a whole and provides criticisms and suggestions for its future growth. The Board regards the Nano-Tera.ch program as a unique blend of technology exploration and system design. The scientific and industrial challenges studied in the program are related to exploiting micro and nano components within complex systems whose added value is much larger than the sum of their parts. A notable example is networked sensors for medical and environmental applications. Networking boosts the intrinsic power of local measurements, and allows us to reach new standards in health and environment management, with positive fallout on security of individuals and communities.

Smart and diversified energy generation, such as harvesting and low-power system design are of the utmost importance to society and the economy. Truly innovative approaches are needed, that can only be found by massively investing in engineering research. Thus the Board lauds the extension of the Nano-Tera.ch scope to include energy as an application area.

The upcoming scientific and engineering challenges are too heterogeneous and complex to be solved within a single scientific domain. They require a truly collaborative and cross-disciplinary approach. The Nano-Tera.ch program brings together excellent researchers in various fields from many Swiss institutions with outstanding reputation.

The program is not only of high scientific value but also of eminent economic importance for the industrial sector of Switzerland. The program serves as the seed for truly innovative products and industries. It also fosters the education of highly-qualified engineers and researchers who are the most valuable and indispensable resource of this country.

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Nano-Tera.ch kick-off meeting.(L-R) Nano-Tera.ch Program Leader G. De Micheli, Secretary of State M. Dell’Ambrogio, EPFL President P. Aebischer, ETHZ Vice President G. Schmitt

“ Nano-Tera.ch has provided new and important research opportunities as an instrument

for application oriented collaboration in engineering that did not exist before, and that

foster very challenging systems engineering projects. The panel is impressed and pleased

about the current state and progress of the program. The projects demonstrate that

collaboration of leading scientists is effective and essential to break new grounds for

large technical and societal challenges. It forces scientists to think about how to integrate

their scientific findings in such a manner that it can be used for industrial applications.

The program has supported the shift in the mindset from individualistic towards

multidisciplinary and cross-disciplinary research.”

2011 evaluation of the Nano-Tera.ch program by the sNf Evaluation Panel

“ We congratulate the researchers and the management for their outstanding work and

program. The SAB members consider the Nano-Tera.ch program of top quality with

respect to management and projects when compared to international programs.”

2011 evaluation of the Nano-Tera.ch program by the Scientific Advisory Board

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ExECuTiVE SuMMARy

Nano-Tera.ch is a Swiss national program supporting research in engineering of complex (tera scale) systems for health, security and the environment using nanotechnologies. Recent emphasis has been also placed on energy issues as a central theme affecting system design, society and the economy. The program is funded by the Swiss Secretary of Education and Research (SER), in collaboration with the Swiss Polytechnic and University Boards (ETH Board and CUS). The Swiss National Science Foundation (SNSF) evaluates and monitors research projects through an international panel of experts.

Officially launched in February 2008, with first projects starting in March 2009, Nano-Tera.ch is now a strongly established program that is currently funding 68 research projects for a total budget of about 123 MCHF over four years. The funded projects are typically carried out by teaming 3 to 9 research groups belonging to various Swiss Research and Education institutions (i.e., Polytechnics, Universities and Research Centers) as well as industries, thus building a network of 31 Swiss research institutions involving a total of more than 600 research staff members.

At the scientific level, the funded research has generated about 300 publications and more than 500 presentations at conferences and workshops worldwide, as well as several presentations in general public media (television, radio, press). A total of 14 awards have been received by Nano-Tera.ch researchers, including 10 best paper/poster awards and 4 awards for personal achievements. Furthermore, both the evaluation carried out by the SNSF Evaluation Panel of international experts and the Nano-Tera.ch Scientific Advisory Board have stressed the scientific excellence of the funded research and the researchers involved, as well as the strong contribution of the Nano-Tera.ch program to the multidisciplinary development of Swiss engineering sciences.

At the international level, Nano-Tera.ch has contributed to several symposia, courses and seminars in collaboration with worldwide partners. For example, Nano-Tera.ch has hosted American, European and Asian scientists in workshops and seminars. In 2011 the program launched a strategic initiative aiming at encouraging Sino-Swiss research collaborations within Nano-Tera.ch thematic areas. This initiative benefitted from the agreement existing between the Chinese Academy of Sciences and the Sino-Swiss Science and Technology Cooperation (SSSTC) program supported by the SER, and took the form of a competitive call for collaborative Sino-Swiss projects that led to the approval of 6 joint projects.

From an industrial perspective, most of the large Nano-Tera.ch research projects receive support from the private sector. Currently 27 industrial partners provide a total budgeted amount of about 6.3 MCHF of in-cash and in-kind contributions, and 8 patent applications have already been filed for results generated in Nano-Tera.ch projects.

The Nano-Tera.ch results are also starting to raise public awareness about the achievements made in the program, with reports broadcast on national TV and Radio networks (SF, TSR, and RSR), articles published in national press (the “Neue Zürcher Zeitung” and “Le Temps” newspapers) and news disseminated in international newswires (e.g. CNN). Similarly, the attention of political actors is increasing, with, for example, the handover at the CeBIT 2011 industrial fair of an interlayer cooled chip 3D-stack (related to the project CMOSAIC) to the German chancellor Angela Merkel.

Looking to the future, the program is getting to the end of its first phase (2008-2011, extended to 2012), and now preparing the second one (2013-2016). Topically, the program will keep its focus on health, security and environment, with an extension to smart energy management, a field that is tightly related to environmental issues. Moreover, it will further strengthen the overall cohesion of the research efforts and progressively emphasize the applied aspects of the research being carried out. In this perspective, the main objectives of the second phase of the program will be to take advantage of the gained momentum to pursue excellence in collaborative research in engineering disciplines, to continue educational programs, to foster the design of applied demonstrators, and to prepare the transfer of research results to the Swiss industry.

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iNTroDuCTioN

The objective of the Nano-Tera.ch program is to support research, design and engineering of complex systems and networks using micro/nano-technologies. More precisely, the program aims at identifying and fostering potential synergies between micro/nano component technology (the “nano” part) and large-scale system design (the “tera” part) to meet the growing need for complex engineered solutions to socially relevant issues related to Health, Security, Environment, and Energy. Examples of such issues are detecting in real time different health risks and conditions through integrated bio probing, revealing security risks through smart buildings and environments, saving energy through ambient sensing, or detecting and monitoring environmental hazards such as floods or avalanches. Embodiments of such solutions will typically take the form of lightweight, mobile and personalized products embedded in the environment and on/in the human body.

Nano-Tera.ch extends the success of other national research programs, such as the National Centers of Competence in Research (NCCRs) by bringing a coordinated strategy to exploit, extend and integrate the skills available at various Swiss academic and R&D centers to foster collaborative scientific research in engineering disciplines, create and expand educational programs, construct demonstrators of the studied technologies and transfer the results to the Swiss industry.

To meet the objectives mentioned above, Nano-Tera.ch supports three types of projects:

Research, Technology and Development (RTD) projects, representing about 80% of the Nano-Tera.ch activities, are large integrated, interdisciplinary research projects involving a collaboration between two (or more) research groups, preferably from different institutions. RTD projects typically focus either on the in-depth study of a particular vertical technology or on the development and implementation of a horizontal application area. The expected duration of RTD projects is 3 or 4 years, with total budgets in the range of 1-2 MCHF/year.

Nano-Tera.ch Focused (NTF) projects are small-scale research projects addressing specific scientific/technical issues and needs. Their typical duration is about 1 year, with total funding in the range of 100-200 kCHF.

Education and Dissemination (ED) activities correspond to actions aiming at supporting short courses, workshops, mini-conferences, and developing new curricula in domains covered by Nano-Tera.ch that are not provided by Swiss Universities and Polytechnics. ED activities may address the in-depth study of a technology or interdisciplinary horizontal activities, and their typical funding level is in the range of 15-30 kCHF.

The Nano-Tera.ch program is funded by the Swiss Secretary of Education and Research (SER), in collaboration with the Swiss Polytechnic and University Boards (ETH Board and CUS). The Swiss National Science Foundation (SNSF) evaluates and monitors research projects through an international panel of experts.

Overall resultsAfter over two years of full operation, the Nano-Tera.ch program is now funding 68 research projects: 19 RTD projects, 8 RTD add-on projects, 15 NTF projects, 6 Nano-Tera.ch Sino–Swiss collaboration projects and 20 ED activities, for a total budget of about 123 million Swiss francs. A description of each of the projects can be found in the second part of this document.

These projects are carried out by consortia of 3 to 9 research groups, building a network of 31 Swiss research institutions, involving a total of more than 600 staff members. As illustrated by the figure below, this network represents a very dense geographical coverage of Swiss research institutions.

Geographical coverage of the Nano-Tera program. The size of the nodes is proportional to the number of involved research groups and the thickness of the lines measures the number of collaborations.

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Scientific disseminationThe research funded by Nano-Tera.ch has generated about 300 publications and more than 500 presentations at conferences and workshops. The distribution of the publications by type, as well as the geographic location of the attended conferences are given below.

A total of 14 awards have been received by Nano-Tera researchers, including 10 best paper/poster awards and 4 awards for personal achievements:

- The 2010 ASME Heat Transfer Memorial Award to Prof. Thome (CMOSAIC project) for his career contributions to two-phase heat transfer in the macro and micro-scale;

- The 2010 Erwin Schrödinger Prize for Interdisciplinary Research of the Helmholtz Society to Jan Roelof van der Meer, Hauke Harms and Mona Wells (LiveSense project) for their development of bacterial reporter assays to detect arsenicals in drinking water;

- The 2011 Science Prize of the State of Basel to Prof. Dr. Christoph Gerber (PATLiSci project) for his pioneering work in the field of nanotechnology;

- The 2012 Life time Achievement Award of Nature Publishing Group to Christoph Gerber (PATLiSci project) for his achievements in AFM technologies.

In addition, in 2011, Prof. De Micheli and Prof. Thiele, members of the Nano-Tera.ch Executive Committee, have been elected to the Academia Europea for their work in Informatics.

Collaboration with the industryMost RTD projects receive support from various industrial partners that are actively involved in the projects and contribute to research and development either directly (in cash) or by in kind contributions (personnel, equipment ...). Altogether, 27 industrial partners, representing a good mix of large companies and smaller structures such as start-ups, are involved in Nano-Tera.ch RTD projects and their extensions, for a total budgeted support of about 6.3 MCHF of in-cash and in-kind contributions.

As far as patenting is concerned, 8 patent applications have been filed so far for results obtained within Nano-Tera.ch RTD and NTF projects and two additional patent applications are in preparation.

Publication statistics by project type since the start of the program

Geographical distribution of presentations of Nano-Tera results given at conferences and workshops

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MAiN SCiENTiFiC ACHiEVEMENTS

hEaLTh MaNaGEMENT Future health management systems will require an increasingly large presence of automation, information extraction and elaboration, as well as control of the medical procedures. In essence, three major innovation areas can be envisioned: biosensing, advanced diagnosis tools, and medical care support.

BiosensingAlthough some biosensors are already available on the market, there is a strong potential for improvement of the techniques used to perform bio-measurements, for example by exploring novel sensing mechanisms, by using advanced electronic devices and materials, or by tightly coupling electronic sensing to data acquisition chains.

In this perspective, Nano-Tera.ch projects are exploring different avenues:

Building sensing platforms based on optical near and mid-infrared range spectroscopy that exploit optical absorption properties of the analytes. In such platforms, the sensors probe the vibrational frequencies of molecules present in fluids and gases. A typical example of such an approach is the IrSens project that aims at detecting cocaine in human saliva as well as the helicobacter pylori, a bacterium responsible for gastric ulcers, in exhaled breath.

Developing modular sensor platforms using silicon nanowire (SiNW) field-effect transistors, interfaced to electronics and micro-fluidic channels for liquid handling. As illustrated in the NanowireSensor project, one of the important advantages of such platforms is that the sensors have the potential to be mass manufactured at reasonable costs, allowing their integration as the active sensor part in electronic point-of-care diagnostic devices.

Health monitoring systems combining networked databases with on-line (i.e. real-time) wearable/implantable monitoring devices represent a true potential for better therapy and increased autonomy of the patients. However, few systems with on-line biosensing capabilities are currently available, and are often limited to either wearable devices for human telemetry (accelerometers, heartbeat monitoring, etc) that do not measure any molecular metabolites, or glucose monitoring systems for diabetic patients. For other needs, blood sampling and off-line analysis are used and require large and expensive laboratory equipments Designing accurate and affordable biosensing devices able to provide fast response and secure interaction with on/in body electronics, as well as to detect and quantify multiple compounds in parallel several times a day thus represents a crucial area of research.

An example of the research developed in Nano-Tera.ch in this direction is the i-IronIC project, which aims at designing an on-line implant for real-time monitoring of various human metabolites (such as lactate, cholesterol, ATP, glutamate, or glucose). The current i-IronIC prototype includes a sensor array, a CMOS mixed signal chip and a tridimensional integrated coil for receiving inductive power and transmitting data via backscattering. The sensor array is realized with an innovative technology, where carbon nanotube (CNT)-nanostructured electrodes enable the measurement of metabolites with increased sensitivity and lower detection limits as compared to the state of the art.

Advanced diagnosis toolsAdvanced diagnosis requires the design of new methods for probing the human body, as well as the design of miniaturized (thus portable) diagnosis tools that can be made easily available at points of care. In this perspective, Nano-Tera.ch projects are focusing on the following challenges:

Designing novel techniques for the diagnosis of human tissues based on micro-mechanical sensing, similar to atomic force microscopy scanning. Indeed, the measurement of nano-mechanical properties of cells and cell-cell interactions as a function of milieu parameters offers unprecedented insights into the tissue structure and is of particular interest in cancer research, where it has been recently shown that stiffness of cancer cells affects the way they spread in the body. The PATLiSci project is an example of a Nano-Tera.ch research in this direction.

Building integrated lab-on-a-chip platforms able to monitor and investigate various metabolic functions of the human body. In particular, the NutriChip project focuses on food digestion with the design of a prototype of an artificial and miniaturized gastrointestinal tract using a minimal set of biomarkers identified through in vivo and in vitro studies. Such a prototype offers novel perspectives for probing the impact on health of dairy food samples, and will be tested for the screening and selection of dairy products with specific health-promoting properties.

Developing miniaturized X-ray sources based on multi-walled carbon nanotube (MWCNT) cold-electron emitters. When combined with novel image processing techniques exploiting X-ray time-of-flight measurements (to probe the depth inside objects), as well as the specific pixel structures of both the X-ray source and the X-ray detector, such approaches open very interesting possibilities for the design of portable X-ray systems with fully unprecedented tomographic imaging capabilities. The Nexray project is an illustration of such a research track in the Nano-Tera.ch program.

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Medical care supportThe general area of monitoring systems for medical care support represents an extremely rich research domain with multiple research directions:

Electronic textiles relying on advanced (electrical/optical) fibers incorporating sensors, signal transmitters and other active nano-components provide very interesting possibilities for implementing body area networks where both sensing and communication are integrated in the same medium. In this domain, the Nano-Tera.ch TecInTex project aims at the development of such a technology demonstrator, embodied in an electronic underwear for paraplegic people able to prevent pressure ulcers (which typically occur twice a year for these patients), thus entailing an important reduction of pain and associated health care costs for such patients.

Smart prostheses integrating innovative micro-devices to measure in vivo crucial bio-mechanical parameters of joint prostheses, orthopedic implants, bones and ligaments. For example, the Nano-Tera.ch SImOS project focuses on the design of an implant module including sensors to measure forces, interface frictions, stem micro-motion and impacts to help surgeons with prosthesis alignment and positioning during surgery, detect early migration during rehabilitation, thus potentially avoiding failure due to excessive wear or micro-motion information, and evaluate in vivo joint functions. Such capabilities represent a potentially huge progress in the domain of hip and knee prostheses, since over a million prostheses are currently implanted each year in the EU and the US, with a premature failure rate of about 20% (for people less than 50 years old) translating into a substantial amount of complex and traumatic revision surgeries.

Smart drug delivery based on drug response monitoring through the in vivo measurement of drug concentrations and relevant biomarkers. Indeed, medical progress is increasingly improving the survival rate and life quality of patients affected by long-lasting diseases, such as HIV infection, cancers, or vital organ failures. But these achievements significantly rely on drug regimens and therapeutic protocols that require long-term daily administration of highly active drugs, for which the huge individual response variability raises severe problems in efficient treatment definition. In this perspective, the Nano-Tera.ch ISyPeM project aims at providing advanced technologies for seamless drug monitoring and delivery by an ultra-low power integrated system.

ENViRoNMENTAL MoNiToRiNGWithin Nano-Tera.ch, the objectives of the research on environmental monitoring include monitoring the quality of air and water, by measuring pollution in terms of biological and/or inorganic compounds; and instrumenting the environment to detect movements that can lead to catastrophes, such as rockslides, avalanches, floods or to the instability of constructions such as buildings and bridges.

Monitoring water pollutionThe quality of water is crucial for both developed and developing countries, as it directly affects health and quality of living. The design of efficient, reliable and affordable technologies to measure levels of pollution in fresh waters is therefore an important problem.

In this perspective, Nano-Tera.ch research is focusing on environmental sensing based on living cells. Indeed, living cells are the most natural biosensors, since they integrate the biological effects of the pollutants and respond by metabolic or phenotypic changes that are relevant to potential effects in the human body. More precisely, the general idea behind living cell-based sensors is that cellular responses are measured in real time by secondary probes or sensors integrating optical, chemical or electrical microsensors.

For example, the Nano-Tera.ch LiveSense project aims at designing a cell-based sensing platform taking the form of an autonomous, wireless, hand-held system for fluid monitoring. The modular prototype includes a fully functional bioreactor based on genetically modified E. coli cells (HepG2/C3A hepatocytes) and cells derived from human epithelial colorectal adenocarcinoma (C2BBe1 cells), for which storage and culture protocols have been established and sensitivity to various target analytes characterized; as wellas various secondary sensors for fluorescence, impedance, and mechanical/trans-epithelial resistance. The prototype (which can be remote controlled with a smart phone) has been validated by characterizing the relation between measured fluorescence intensity and the concentration of arsenic in the analyzed water sample. In addition, label-free techniques to distinguish healthy, sick and dead cells have been designed, making it possible to detect cellular changes long before cellular death, thus offering a high sensitivity in comparison with conventional viability assays.

Nano-Tera.ch 9

Monitoring air pollutionWireless sensor networks publishing sensor data on the Internet bear the potential to substantially increase public awareness as well as involvement in environmental sustainability. Air pollution monitoring in urban areas is a prime example of such an application, as air pollutants have a direct effect on human health.

The Nano-Tera.ch OpenSense project is an example of research on air pollution monitoring. It focuses on the design of a network of mobile air pollution sensors with intermittent GPRS connectivity, deployed on top of public buses in the city of Lausanne and on top of trams in the city of Zurich. The prototype sensor network is now operational and provides valuable insights on sensor capabilities and behaviors in realistic environments. The generated network and air pollution data is used for the various modeling tasks (mobility, air pollution, etc) that have been identified as key challenges in the project and the resulting models in turn serve for generating numerical input that can be used for efficient signal processing and machine learning. In addition, a collaboration with the Nokia Research Center in Lausanne led to the set up of user studies that clearly demonstrated both the public interest for air pollution data and the commercial potential of the developed technology.

Monitoring rock and glacier movementsGlobal climate change dramatically influences the visual appearance of mountain areas like the European Alps, and may trigger or intensify destructive geological processes that impact the stability of slopes, thus posing a threat to local communities.

In this perspective, research in Nano-Tera.ch is focusing on the development of wireless sensing technologies for environmental sensing under extreme environmental conditions (temperature, humidity, mechanical forces, snow coverage, etc). In particular, in the Nano-Tera.ch X-Sense project, various rugged electronic chips have been built to install more than 50 sensors in the Mattertal area of Switzerland. The corresponding prototype of wireless sensor network and GPS data processing framework has been deployed with improved system reliability and data quality derived from model-based design principles. Data have been collected and are currently undergoing geophysical analysis, as well as being used to produce models for the understanding of the processes governing terrain movement in alpine environments.

ENABLiNG TECHNoLoGiESIn some cases, research and development may impact several areas in the health and environment domains, and some of the Nano-Tera.ch projects are therefore focusing on generic enabling technologies.

For example, the Nano-Tera.ch MIXSEL project is investigating the use of laser sources to create short pulses that can support microscopy and optical tomography. Similarly, the CabTuRes project studies new materials, such as carbon nanotubes (CNTs),using them as resonators for electronics applications as well as mass balances for sensing.

Heat management in high-performance multi-processing systems, realized as 3-Dimensional Integrated Circuits is another generic track of research, and, in this domain, the Nano-Tera.ch CMOSAIC project combines competencies in thermodynamics, mechanics of materials, and dynamic power management to design liquid cooling techniques specifically tailored for 3D chips.

On the other side of the spectrum, research in Nano-Tera.ch also concentrates on low-power electronic systems, and specifically autonomous systems, that are crucial for both health and environment applications. In this perspective, the Nano-Tera.ch PlaCiTUS project focuses on the design of a generic technology platform that can be used to deploy biomedical wireless sensor networks. Such a platform typically consists of many sensors and actuators connected together and to the outside world, through a short range wireless network, and interfaced with micro-power data acquisition and driver circuits supplied either by battery or by inductively coupled remote power. The additional integration in the platform of a low power Wide Area Network modem makes it possible to also periodically communicate with remote health centers to transmit data that require more complex analysis.

Another critical issue is the manufacturing of integrated nano-systems consisting of large numbers of connected nano-devices. The Nano-Tera.ch SelfSys project studies fluid-mediated self assembly techniques to lower manufacturing costs and enable the assembly of structures with unprecedented complexity.

Finally, in the security domain, the Nano-Tera.ch QCrypt project aims at improved secret key distribution and message encryption based on the fundamental properties of quantum physics (Quantum Key Distribution), and, in the energy domain, the GreenPower project aims at the development of cost-effective membranes for H2-O2 fuel cells suitable for mobility applications based on the conversion of solar energy into hydrogen and oxygen.

MAiN SCiENTiFiC ACHiEVEMENTS

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The Swiss delegation and their Chinese hosts at Fudan university, Shanghai

Geographical locations of 7 Chinese partners in 5 institutions

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iNTErNaTioNaL ouTrEaCh

Nano-Tera.ch is regularly present at various international scientific events. Members of the Nano-Tera.ch Executive Committee are asked to deliver keynote speeches and presentations on the Nano-Tera.ch program (e.g. Prof. G. De Micheli in Santa Clara, USA, November 2008, Grenoble, France, March 2011, Dalian, China, April 2011, Seoul, South Korea, November 2011 and in Sydney, Australia, January 2012). Members of the Nano-Tera.ch Management Office are holding booths at various international conferences (e.g. the DATE conference 2011 in Grenoble, the Transducers 2011 conference in Beijing, or the Eurosensors 2011 conference in Athens).

Nano-Tera.ch booth at the Transducers 2011 conference, Beijing

The various Education and Dissemination activities funded by Nano-Tera.ch also represent good opportunities for attracting the attention of international audiences on the Nano-Tera.ch program. For example, the 132 participants to the International Symposium on Medical Information and Communication Technology (ISMICT 2011) partly funded by Nano-Tera.ch came from 21 different countries, including Switzerland, Japan, Canada, the US, France and Finland.

Furthermore, the ED activities are often a very good opportunity for introducing the program to leading academic and industrial experts and fostering the links between these experts and the Swiss Nano-Tera.ch community.

For example, the Nano-Tera.ch "Beyond the Brick Wall of Complexity" workshop, organized in January 2012 at EPFL aimed at: bringing together the foremost authorities in the world of semiconductor technology and design in order to pinpoint the shortcomings of the current design methodologies and CAD tools; identifying new problems that may lie ahead; providing a vision of the new CAD tool capabilities that are going to be required; and proposing a new paradigm for design methodologies that fully exploits the potential of new process technologies. During this outstanding event, world class experts were present: Luca Benini (STMicroelectronics/University of Bologna), David Blaauw (University of Michigan), Vivek De (Intel Corporation), Steve Kang (University of California, Santa Cruz), Kaushik Roy (Purdue University), Rob Roy (Atrenta Inc.), Sachin Sapatnekar (University of Minnesota) and Costas Spanos (University of California, Berkeley).

These experts have intensively interacted with the members of the Nano-Tera.ch community, thus strengthening the international impact of the program.

Similarly, the 2010 Nano-Tera.ch tutorial on "Manufacturing, Design, and Thermal Issues in 3-D Integrated Systems" contributed to highlight the important strides that have recently been made in the emerging research field of 3-D integration. The presentations made by renowned international speakers from both academia and industry (e.g. the French LETI), as well as by researchers from the Nano-Tera.ch CMOSAIC project, was an excellent opportunity to strengthen the international networking of the Nano-Tera.ch program and to disseminate the research results generated in Nano-Tera.ch to the international community.

Sino-Swiss collaborationsIn 2011, Nano-Tera launched an initiative aiming at creating synergies to encourage Sino-Swiss research collaborations within Nano-Tera.ch thematic areas.

An important first step took place in November 2010, when Nano-Tera.ch, on the initiative of Executive Committee member Prof. Boi Faltings, took part to a tour of Chinese institutions to initiate a dialog on possible future collaborations. In addition to Prof. Faltings, the Swiss delegation included Dr. Patrick Mayor, scientific coordinator of Nano-Tera.ch, with support provided by Dr. Lan Zuo Gillet and Dr. Claudio Boër of Swissnex China as well as Prof. Denis Gillet of EPFL.

The collaboration of Nano-Tera.ch in China with the Chinese Academy of Science (CAS) benefitted from the existing agreement between CAS and the Sino-Swiss Science and Technology Cooperation (SSSTC) program, which is hosted by the ETHZ and supported by the State Secretariat for Education and Research for the promotion of bilateral science and technology cooperation with China.

Following this first exploratory phase, a joint call for Sino-Swiss Pilot Grants was launched in Spring, 2011 combining the strengths of Nano-Tera.ch and SSSTC.

In order to support the initiative and increase Nano-Tera.ch visibility in China, a booth presenting Nano-Tera.ch activities and promoting the call was set up at the large Transducers conference which was held in Beijing in early June 2011 and included several Nano-Tera investigators, thus initiating discussions between Swiss and Chinese scientists.

The evaluation made by the Nano-Tera.ch Executive Committee of the submissions to the call led to the selection of 6 projects for a total budget of about 1.5 MCHF, including Swiss and Chinese own contributions.

All projects started on October 1st, 2011 for a duration of 12 months.

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Nano-Tera main page

Comparative web statistics for the period october - November 2010 (green) and November - December 2011 (blue).

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DiSSEMiNATioN AND PRoMoTioN ACTiViTiES

Photograph of the CeBiT - demonstrator visualizing an interlayer cooled chip stack with four-port fluid delivery and non-uniform heat removal cavities (dies are partially removed, to get visual access to individual layers). Demonstrator hand over from iBM CEo Sam Palmisano to chancellor of Germany: Angela Merkel.

Nano-Tera websiteThe Nano-Tera website (www.nano-tera.ch) represents an important dissemination channel for the Nano-Tera program. The number of visits to the site is monitored and used for decisions related to information dissemination.

Nano- Tera.ch in the newsThe results generated in the framework of the Nano-Tera.ch program are starting to raise public awareness about the achievements made in the program, with reports broadcasted on national TV and Radio networks (SF, TSR, and RSR), articles published in national press (the “Neue Zürcher Zeitung” and “Le Temps” newspapers) and news disseminated in international newswires (CNN news). For example, the BioCS-node, an autonomous tool, jointly developed by the Embedded Systems lab and the Telecommunications Circuits lab at EPFL, that automatically identifies anomalies in heart-rate, and automatically alerts doctors to help them treat patients more quickly (see pictures below) has raised substantial interest in the digital media world-wide.

Other RTD projects have also generated interest in various media. For example, the Swiss national newspapers “Le Temps” and “Neue Zürcher Zeitung” dedicated articles to the results on smart textiles obtained within the TecInTex project, while the Swiss national TV SF1 featured a report on knee replacement surgery based on technologies produced within the SImOS project and the Swiss national TV TSR1 and radio RSR1 broadcasted reports on anti-inflammatory nutriment screening using the lab-on-a-chip platform developed within the Nutrichip project.

Similarly, the attention of political actors is also increasing, with, for example, the handover at the CeBIT 2011 industrial fair of an interlayer cooled chip 3D-stack to the German chancellor Angela Merkel (see picture below). 3D-stacking technologies and their cooling is currently studied by RTD project CMOSAIC, grouping scientists from EPFL, ETHZ, and IBM Research.

Portable heart monitoring device

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Nano-Tera Annual Plenary MeetingsEvery year Nano-Tera.ch organizes an Annual Plenary Meeting showcasing the supported research projects.

These meetings feature keynote presentations in the domains covered by Nano-Tera.ch (e.g. the talk given by Dr. Rudy Lauwereins, CTO of IMEC on “The Wetware-Hardware Interface:three ways of interfacing our brain to a computer” in 2010, and by Dr. Bruno Murari of ST Microelectronics on “Lateral thinking: the impact of breakthrough innovation” in 2011), as well as oral presentations of all the RTD projects by their principal investigators. The meetings are usually organized over two days and attract over 250 participants.

In addition to the oral presentations, posters are also presented by researchers involved in the projects.

Poster session at the Nano-Tera.ch Annual Plenary Meeting

Other dissemination/promotion activitiesNano-Tera produces a promotional brochure detailing all running projects.

The presentations made at the Annual Plenary Meeting are filmed and converted into a promotional video available on DVD and online.

A Nano-Tera Newsletter is disseminated by email to the Nano-Tera community and made available on the website (http://www.nano-tera.ch/news/newsletter.html).

Cover of the 3rd edition brochure

online video of project presentation

Nano-Tera.ch 15

The initial phase of the Nano-Tera.ch program (2008-2012) addressed advanced research for health, security and the environment, which requires the meaningful and efficient acquisition, processing, transmission, management and integration of data coming from a very large number of heterogeneous sources. Thus, the scientific unifying theme of this program was to design and demonstrate large-scale networks that combine information coming from different sources, such as bio-medical information, physical quantities, audio-visual-sensorial information, etc.

In its second phase (2013-2016), the Nano-Tera.ch program will continue and expand interdisciplinary projects involving researchers from different universities/research centers and from different research fields, with the goal to address design and engineering of complex information systems.

The targeted research space (see figure below) consists of initial applications areas (wearable and implantable systems, ambient and environment systems), with an important extension to energy systems, an application field tightly related to environmental issues and to the design of autonomous systems. These application areas intersect a set of basic engineering technologies (Nano electronic devices and circuits, Nano/Micro Electro Mechanical Systems (M/NEMS) and sensors, Software and systems and Communication) that illustrate the importance for the Nano-Tera.ch program to continue to produce embodiments of research results into prototypes that can act both as demonstrators and as technology drivers.

Besides research projects, the Nano-Tera.ch program will also continue to educate doctoral students. In this perspective, Nano-Tera.ch intends to broaden the doctoral program offered at various Swiss universities to achieve the breadth and depth typical of their American counterparts. This goal will be achieved by creating courses that can be offered to all graduate students of the participating institutions. Co-teaching in joint courses will be encouraged. Innovation in teaching will be based on blending ex cathedra instruction with lab experimentation and with the creation of engineering projects to develop new technologies and applications. Nano-Tera.ch will also support the creation of Summer schools, with the objective of gathering scientists and instructors to offer condensed instructional programs on specific topics. Such schools will be targeted to graduate students and junior researchers in academia and industry.

Finally, another major innovation with respect to the initial phase will be the formation of new partnerships between the Nano-Tera.ch consortium and the private sector, to favor the creation of high added-value systems exploiting the created technologies. This form of technology transfer to the Swiss industry will be achieved through collaborative projects and through targeted interaction. In this perspective, the general objective of the Nano-Tera.ch program is to foster the re-industrialization of Switzerland and to strengthen the Swiss leading position in the development and industrial exploitation of electronic systems that address health, environment, security and energy issues.

NExT PhasE (2013-2016) of ThE NaNo-TEra.Ch ProGraM

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Y. Leblebici

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P. Fischer

A. Ionescu

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MicroCool J. Thome p.105

B-AWaRE M. Ruggiero p.105 SEE-Nano Mastering-NT

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SPIMD S. Carrara p.105

MMB2011 O. Guenat p.105 TED-Activities EASY

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iCAN J. Brugger p.104

ISMICT C. Enz p.105 NextGen FEDAMaTp.103

C. Enz COMES M. Sami p.104

WIMEMS-School QCrypt-ED E-Print

D. Briand

M. Christandl

G. Nisato

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Nexray / COSMICMOS A. Dommann

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OpenSense / OpenSense+

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NanoBio2010 J. Vörös p.104

O. Martin

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PlaCiTUS QCrypt

IrSens / IR-N-ox J. Faist

ISyPeM / TWPeM C. Guiducci

PATLiSci / MINACEL

NutriChip / Ca-NutriChip

2013

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P. Vandergheynst

M. Schumacher

TWIGS D. Briand

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SelfSys / SelfSys+ J. Brugger

SMTS C. Dürager p.100

ULP-Systems Y. Leblebici p.101

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PMD-Program S. Maerkl p.100

ULP-Logic Y. Leblebici p.101

SecWear M. Sami p.100

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NanoUp p.99

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MicroComb p.98

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CabTuRes C. Hierold

CMOSAIC J. Thome

GreenPower i-IronIC

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CabTuResEnabling autonomous sensor nodes: low-power nano-sensor/electronics building blocks based on tunable carbon nanotube electro-mechanical resonators

PrinciPal investigator

Prof. Christofer Hierold, ETHZ

co-aPPlicants

Prof. Wanda Andreoni, EPFL

Prof. Nico de Rooij, EPFL

Prof. László Forró, EPFL

Dr. Oliver Gröning, EMPA

Prof. Adrian Ionescu, EPFL

Prof. Maher Kayal, EPFL

Prof. Bradley Nelson, ETHZ

Prof. Dimos Poulikakos, ETHZ

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CabTuResENABLING AuTONOMOus sENsOR NODEs: LOW-POWER NANO-sENsOR/ELECTRONICs BuILDING BLOCKs

BAsED ON TuNABLE CARBON NANOTuBE ELECTRO-MECHANICAL REsONATORs

GoalsSensors are becoming ubiquitous in our lives and possible applications are countless. Micro and nanotechnologies are the natural choice for enabling complex sensor nodes, as they are small (thus unobtrusive), cheap and low power. Carbon nanotubes (CNTs) are a perfect example of how nanosystems offer features unachievable with microsystems: their outstanding structural, mechanical and electronic properties have immediately resulted in numerous device demonstrators from transistors, to physical and chemical sensors, and actuators. A key idea of the project is to combine elements from the fundamental knowledge base on the physics of carbon nanotubes, gathered in the past several years, and the fundamental engineering sciences in the area of micro/nano-electromechanical systems, to develop novel devices and processes based on CNTs.

Specifically, it seeks to demonstrate concepts and devices for ultra-low power, highly miniaturized functional blocks for sensing and electronics. Due to their small mass and high stiffness, doubly clamped CNTs can exhibit huge resonant frequencies. These are carbon nanotube resonators which, as recently demonstrated or predicted theoretically, can reach the multi-GHz range, can be tuned via straining over a wide range of frequency, offer an unprecedented sensitivity to strain or mass loading, and all these with a very low power consumption.

Two specific applications are being targeted. First of all, because of their high Q × f figure of merit, carbon nanotube resonators offer a wide range of electronics applications, where they can be used as tunable voltage controlled oscillators, clocks or nano electro-mechanical filters and detectors. Another application is mass balances for sensing: since mass loading creates a shift in resonant frequency, with huge sensitivity to tiny mass variations, the resonators can be used to measure gas molecule densities or weigh nano bodies such as proteins and viruses. And as the resonant frequency is also affected by strain in the CNT, strains and forces could be measured in a rather straightforward manner.

The outcome may have implications in several domains: it will support health in diagnosis or preemptive detection of air borne pathogens and advance the basic science of proteomics, genetics and virology. Besides, autonomous, ultra-small and ultra-low power sensors could find their way in many wearable, ambient or remote systems.

• physics of carbon nanotubes novel CNT-based devices: ultra-low power, • engineering sciences in N/MEMS miniaturized functional blocks for sensing & electronics

Using CNT-based nano electro-mechanical resonators: CNTs have small mass & high stiffness when doubly clamped: huge resonant frequencies reachable (>1GHz)

Novelty:

• better tuning via appropriate tensile actuators (uncontrolled chirality may not affect tunable CNT resonators)• process flow allowing combination of MEMS with CNTs &CMOS ICs plethora of applications possible

MASS BALANCES FOR SENSINGMass loading creates shift in resonant frequency- with huge sensitivity to tiny mass changes Measure gas molecule densities Weigh nano bodies (proteins, viruses...) Strain also affects resonant frequencies Measure strain/stress/pressure...

ELECTRONICS APPLICATIONSCNTs: higher quality factors than L-C elements CNT resonators could be used as tunable RF voltage controlled oscillators Multi-GHz range also good for NEMS filters and detectors

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ContextState-of-the-art NEMS resonators are mostly made by top-down lithographic techniques and surface micromachining out of various materials such as Si, GaAs, SiN, SiC and AlN. Downsizing mechanical resonators not only leads to an increase of their natural resonance frequencies but their tiny mass reduces drastically the power consumption. However, the native defect density in bulk materials, accompanied by imprecision in fabrication processes results in huge inter-device performance variations. Furthermore, reaching 1 GHz would require clamped beams with diameters in the order of 10 nm, simply beyond the capability of batch photo-lithography. In contrast, bottom-up fabrication approaches now provide routinely nanotubes/nanowires with high crystalline quality and sizes in the order of ~1 nm.

In the field of ultra-small NEMS resonators, carbon nanotubes have as principal competitor crystalline nanowires. However, simple calculations show that CNTs can resonate at frequencies 3-6x larger than SiNWs, at the same cross sectional dimensions, due to both smaller mass and to higher stiffness. For the mass balance application, the mass gain sensitivity (frequency shift to mass shift ratio), is again won by nanotubes because of their smaller effective mass and higher resonance frequencies. To end the list, compared to SiNWs, CNTs have no dangling bonds, have atomic-precise diameter fidelity, have axial modulus independent on the chiral angle (NWs are anisotropic) and have a wider elastic range (NWs are brittle).

In May 2008 when CabTuRes was proposed, there were only four publications on CNT resonators. In the first demonstration, in 2004 Sazonova et al. have reported resonance frequencies of up to 200 MHz and quality factors below 200. Tuning the resonator has been achieved by adding a DC gate voltage to the actuating AC voltage. Peng et al. were the first who managed to cross the 1 GHz resonance frequency barrier (max 1.3 GHz) in ambient conditions. One year later, the same group has reached ~3.8 GHz operation with CNT abacus resonators, with large metal beads deposited along the nanotube having the role to reduce the effective length of the beam. Since then, the number of publications on CNT resonators has constantly increased. Among very recent accomplishments we note mass balance demonstrators with room temperature mass resolution of 25 zg (1 zg = 10-21g) or truly atomic resolutions. This year, Huttel et al. have managed to show that quality factors in the order of 105 can be achieved with CNTs. All these recent accomplishments clearly confirm the theoretical expectations of CNT resonators, providing deeper motivation for the current project. Even in this highly dynamic field, CabTuRes retains its initial originality in proposing a System in a Package concept in which a CNT resonator integrated inside tensile MEMS actuators (not shown before) will be coupled to CMOS IC electronics in an oscillator configuration (not shown before) and properly packaged by a cap wafer (not shown before).

ResultsNovel single-walled carbon nanotube (SWCNT) synthesis processes have to be developed in order to improve the quality of the nanotubes as well as to be compatible with the resonator fabrication process. Also, resulting SWCNTs should exhibit narrow diameter distribution, precise location and controlled direction. A process for forming catalyst particles has been developed that is able to position a single metal particle in an 80 nm2 area. The subsequent nanotube synthesis processes have been shown to result in a narrow diameter distribution and a growth yield close to 100%.

A major project task is to integrate SWCNTs into NEMS and achieve a low contact resistance which is critical for high frequency operation. A silicon-on-insulator (SOI) based process was developed and demonstrated for this purpose. Additionally, in order to preserve the contact resistance over long periods, encapsulation of contacts was found necessary to prevent their oxidation. A passivation process was developed to encapsulate the metal contacts by a thin Al2O3 layer, which was shown in previous studies to be effective in passivating CNTFETs over months. An alternative SWCNT integration process based on dielectrophoresis was developed, that provides precise control on the location, density, orientation and shape of the SWCNTs with sub-50nm accuracy and high yield.

Mechano-chemical clamping at contacts is another important task in the project. Effort was spent in testing the clamp quality of SWCNTs on metal electrodes using nanomanipulation in Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM) and Atomic Force Microscope (AFM). For all these manipulation experiments, SWCNTs had to be suspended between metal electrodes in order to allow access of manipulator probe to the SWCNTs. The integration of SWCNTs was performed with a dielectrophoresis-based process. Good mechanical clamping was shown for palladium (Pd) and gold (Au) top electrodes.

Regarding interface electronics, the front-end was shown to be the critical part of the feed-back loop, setting the noise floor and hence the overall allowed loop bandwidth. A prototype for this circuit was realized and is currently under characterization.

Efforts aiming at gaining experimental and theoretical understanding of the impact of defects on the operation of SWCNT resonators have been focusing on three main topics: chemisorption and vacancy formation on the external surface of single-wall carbon nanotubes; and the development of new interatomic potentials.

Work on system level assembly and encapsulation was focused on three axes: design of a full set of masks and a process flow for the first demonstrator, implementation of this process flow in order to deliver this first demonstrator, and assembling of the CMOS chip to the NEMS resonator.

A patent was filed, named “Piezoresistive static current detection in mechanically vibrating nanoscale sensors”, ETH Invention Disclosure T-10-064.

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PublicationsD. Bercioux, G. Buchs, H. Grabert, and O. Gröning, Defect-induced multicomponent electron scattering in single-walled carbon nanotubes, Physical Review B 83, 165439 (2011).

A. Magrez, R. Smajda, J.W. Seo, E. Horvath, P.R. Ribic, A. Olariu, J.C. Andresen, D. Acquaviva, G. Laurenczy and L. Forró, Striking Influence of Catalyst Support on the Hydrocarbon Chemistry: New Insight into the Carbon Nanotube Growth Mechanism, ACS Nano 5, 3428 (2011).

A. Magrez, J.W. Seo, R. Smajda, M. Mionić and L. Forró, Catalytic CVD Synthesis of Carbon Nanotubes: Towards High Yield and Low Temperature Growth, Materials 3, 4871-4891 (2010).

S. Schürle, M. K. Tiwari, K. Shou, D. Poulikakos, B. J. Nelson, Fabricating devices with dielectrophoretically assembled, suspended single walled carbon nanotubes for improved nanoelectronic device characterization, Microelectronic Engineering 88, 2740-2743 (2011).

J. Cao, A. Arun, A. M. Ionescu, Floating-Potential Self-Assembly of Singe-Walled Carbon Nanotube Transistors by AC-Dielectrophoresis, Microelectronic Engineering 88, 2463-2465 (2011).

J. Cao, C. Nyffeler, K. Lister, A .M. Ionescu, Resist-assisted assembly of single-walled carbon nanotube devices with nanoscale precision Carbon, available online 8 December 2011.

R. Sanjinés, Cr. Vâju, R. Smajda, M. Mionić and A. Magrez, Electrical Properties and Applications of Carbon Based Nanocomposite Materials: An Overview, Surface and Coatings Technology, in press, 2011.

M. Muoth, S.-W. Lee, and C. Hierold, Platform for strainable, TEM-compatible, MEMS-embedded carbon nanotube transistors, 24th International Conference on Micro Electro Mechanical Systems (MEMS 2011), January 23-27, Cancun, Mexico, 83-86, 2011.

S.-W. Lee, M. Muoth, L. Durrer, C. Roman, C. Hierold, Integration of clamped-clamped suspended single-walled carbon nanotubes in SOI MEMS, Proc. IEEE NEMS 2011, 37-40, 2011.

R. Gueye, T. Akiyama, D. Briand, N.F. de Rooij, Development of high temperature platinum TSVs, Procedia Engineering 25, 1513-1516 2011.

M. Muoth, T. Helbling, L. Durrer, S.-W. Lee, C. Roman, C. Hierold, Hysteresis-free operation of suspended carbon nanotube transistors, Nature Nanotechnology 5, 589-592 (2010).

M. Duchamp, K. Lee, B. Dwir, J.W. Seo, E. Kapon, L. Forró, A. Magrez, Controlled Positioning of Carbon Nanotubes by Dielectrophoresis: Insights into the Solvent and Substrate Role, ACS Nano 4, 279 (2010).

A. Magrez, J. W. Seo, R. Smajda, B. Korbely, J.C. Andresen, M. Mionić, S. Casimirius, L. Forró, Low Temperature, Highly Efficient Growth of CNTs on Functional Materials, ACS Nano 4, 3702 (2010).

M. Duchamp, R. Meunier, R. Smajda, M. Mionic, A. Magrez, J.W. Seo, L. Forró, B. Song and D. Tománek, accepted to J. Appl. Phys.

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CMOSAIC3D stacked architectures with interlayer cooling

PrinciPal investigator

Prof. John Thome, EPFL

co-aPPlicants

Prof. David Atienza, EPFL

Prof. Yusuf Leblebici, EPFL

Dr. Bruno Michel, IBM ZRL

Prof. Dimos Poulikakos, ETHZ

Prof. Wendelin stark, ETHZ

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CMOSAIC3D sTACKED ARCHITECTuREs WITH INTERLAYER COOLING

GoalsIndicators show that the speed of transistor density and microprocessor performance improvements that drove the IT industry for the last 50 years are now limited by connectability issues between multiple cores and air-cooling rates. With its CMOS scaling engine slowing, the industry is striving to find new packaging alternatives to maintain the overall pace according to Moore’s law. While 2D scaling has been used in high performance processors for several decades, the third dimension has not yet been tackled. Recent progress in the fabrication of through silicon vias has opened new avenues for high density area array interconnects between stacked processor and memory chips. Such three-dimensional integrated circuits are attractive solutions for overcoming the present barriers encountered in interconnect scaling, thus offering an opportunity to continue the CMOS performance trends over the next few decades.

The CMOSAIC project aims at contributing to the realization of arguably the most complicated system that mankind has ever assembled: a 3D stack of computer chips with a functionality per unit volume that nearly parallels the functional density of a human brain. The aggressive goal is to provide the necessarily 3D integrated cooling system that is the key to compressing almost 1012 nanometer sized functional units into a 1 cm3 volume with a 10 to 100 fold higher connectivity than otherwise possible. Even the most advanced aircooling methods are inadequate for such high performance systems where the main challenge is to remove the heat produced by multiple stacked dies with each layer dissipating 100-150 W/cm2. Therefore, state-of-the-art microscale single-phase liquid and two-phase cooling systems are being developed, using specifically designed microchannel arrangements with channel sizes as small as 50 microns. The employed coolants range from liquid water and two-phase environmentally friendly refrigerants to novel nano-coated, nonwetting surfaces. To this aim, CMOSAIC has brought together a multi-disciplinary team of internationally recognized experts who are jointly conducting research to explore the underlying physics of the proposed cooling mechanisms through experiments and theoretical modelling. The team will also develop all the necessary modelling and design tools needed to simulate 3D integrated circuits stacks during their operation in order to mitigate hot spots, and test various prototype stacks with the goal of identifying and bringing into reality novel methods for heat removal in these high performance systems.

• 3D stacks of computer chips allow a huge functionality per unit volume

• Recent progress in the fabrication of through silicon vias

new ways for high density array interconnects between stacked processor & memory chips

BUT heat needs to be removed ! [each layer dissipates 100-150 W/cm2]These 3D integrated circuits need novel electro-thermal co-design

Microchannels etched on back side of chips to circulate liquid coolant

Interdisciplinary problem approached at various levels: • architecture • microfabrication • liquid cooling • two-phase cooling • nano-fluids

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ContextSeveral indicators show that the rate of increase of transistor density, and thus performance, that have driven the IT industry for the last 50 years is slowing down. Therefore, with its scaling engine slowing, the industry is now scrambling to find new packaging alternatives to maintain the overall pace according to Moore’s law. While 2D scaling has been used in high performance processors for several decades, the third dimension has not yet been tackled. However, recent progress in the fabrication of through silicon vias (TSV) has opened new avenues for high density area array interconnects between stacked processor and memory chips. As a result of this new technology, three dimensional integrated circuit architectures (3D-ICs) have become attractive viable solutions for overcoming the present barriers encountered in interconnect scaling, thus offering an opportunity to continue the CMOS performance trends over the next decade.

Unlike other parameters such as silicon area, operating speed and battery life that mainly affect the performance of an electronic integrated circuit system, a system that does not satisfy thermal requirements will simply not function for very long, making thermal considerations vital for its existence. Furthermore, due to the present rapid development of stacked 3D-IC architectures, such thermal considerations have quickly developed from being a design issue to the key challenge in high density system integration. The main challenge for 3D integration is to remove the very high concentration of heat produced by the stacked microprocessor chips in order to keep their operating temperature below the 85°C critical limit, and to minimise the thermal stresses imposed on the architecture and packaging. For example, each chip on its own produces heat at a rate of 100-150 W/cm2 per layer, so for a stack of ten 2.25 cm2 chip layers this requires 2.2-3.3 kW to be dissipated from a volume of only several cm3. Due to their limited capabilities, standard air cooling techniques are no longer able to cool such systems. As a result of this, there has been a gradual trend towards the development and use of single phase liquid cooling methods, being investigated in detail here with novel geometries and new modelling techniques. Another significant development here is the development of high performance two-phase micro-evaporator interlayer cooling systems that are integrated into the 3D-IC stacks. These will comprise a complex network of numerous microchannels and/or pin fins, in layouts that have never been tried before at this level of sophistication. Furthermore, surprisingly, thermal issues in present practice have so far been addressed independently at different levels of system design and usually after the system architecture has already been defined. To overcome this situation, CMOSAIC will study and address the heat removal problem co-currently at all stages and levels of the design process, including packaging, fabrication, circuit design, and high-level application. The aim of this approach is the creation of a state-of-the-art design methodology for 3D-IC systems which ensures: the system temperature is regulated within its critical limits during its operation by using active simulation and control, and that the available 3D space is filled as efficiently as possible with functional units whilst integrating the cooling system and ensuring high computing performance characteristics.

Review of the patent literature reveals several patents on interlayer cooling have been granted, primarily on some geometrical configurations and fabrication techniques. Research-wise, the CMOSAIC project is very competitive with respect to other teams in the USA and Japan. We have a highly integrated teamwork approach within the project to tackle the difficult multi-disciplinary fluid dynamics, micro-fabrication and modelling issues together, plus the individual labs are also making very significant progress in their own fields of research. This work is highlighted in the partners’ reports below.

ResultsCurrently, extensive teamwork amongst the partners is being used to design and build 2D and 3D experimental test sections to carry out single and two-phase cooling studies in channels as small as 100 μm, to develop computer codes to model the thermal behaviour of these complex flows and chip stacks, to develop suitable surface modification technology to enhance the cooling, and to develop techniques to manufacture through silicon vias, develop sophisticated 3D stack simulation tools, and fabricate 3D chip stack test vehicles with interlayer cooling.

The recent 3D Inter-layer Cooling Emulator (3D-ICE), as part of the 3D IC thermal modeling tools developed within CMOSAC, has been made available as free open source simulator to the EDA community and in only 9 months, there are more than 50 international research groups (including both academic and industrial teams) using it world-wide. Therefore, the ESL members of CMOSAIC have been invited to give several tutorials in the best conferences of the EDA community (DATE, DAC, ICCAD, etc.) to explain the innovation points of this new type of simulation tools and how to use 3D-ICE by system-level engineers for thermal exploration of their 3D ICs (with and without liquid cooling capabilities).

Among significant facts related to the CMOSAIC project:

- CeBIT 2011: Handover of interlayer cooled demonstrator from IBM CEO Sam Palmisano to chancellor of Germany: Angela Merkel.

- Prof. Thome received the ASME 2010 Heat Transfer Memorial Award at the 2010 International Heat Transfer Conference for his career contributions to two-phase heat transfer in the macro and micro-scale.

- Members of ESL-EPFL, partner in the CMOSAIC consortium, have won the Best Paper Award at the 17th Annual IFIP/IEEE International Conference on Very Large Scale Integration (VLSI-SoC), Florianopolis, Brazil, for its paper: “Modeling and Dynamic Management of 3D Multicore Systems with Liquid Cooling” (A. K. Coskun, J. L. Ayala, D. Atienza, T. Simunic,), October 2009.

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PublicationsA. K. Coskun, D. Atienza, M. Sabry, J. Meng, “Attaining Single-Chip, High-Performance Computing Through 3D Systems with Active Cooling”, IEEE Micro Magazine, ISSN: 0272-1732, IEEE Press, Vol. 31, Issue. 4, pp. 63 – 73, DOI: 10.1109/MM.2011.39, July/August 2011.

P. G. Del Valle, D. Atienza, “Emulation-based transient thermal modeling of 2D/3D systems-on-chip with active cooling”, Elsevier Microelectronics Journal, ISSN: 0026-2692, Vol. 42, Nr. 3, pp. 564-571, DOI: 10.1016/j.mejo.2010.08.003, March 2011.

J. V. Goicochea, M. Hu, B. Michel, D, Poulikakos, “Surface Functionalization Mechanisms of Enhancing Heat Transfer at Solid-Liquid Interfaces”, Journal of Heat Transfer 133, 082401 (2011).

Y. Madhour, J. Olivier, E. Costa-Patry, S. Paredes, B. Michel, and J.R. Thome, “Flow boiling of R134a in a multi-microchannel heat sink with hotspot heaters for energy-efficivent microelectronic CPU cooling applications”, IEEE Transactions on Components, Packaging and Manufacturing Technologies, vol. 1(6), pp. 873–883, 2011.

A. Renfer, M. K. Tiwari, T. Brunschwiler, B. Michel, D. Poulikakos, Experimental investigation into vortex structure and pressure drop across microcavities in 3D integrated electronics, Experiments in Fluids 51, 731 (2011).

M. Sabry, J. L. Ayala, D. Atienza, “Thermal-Aware Compilation for Register Window-Based Embedded Processors”, Embedded Systems Letters, IEEE Press, ISSN: 1943-0663, Vol.2, Issue/Nr. 4, pp. 103-106, DOI: 10.1109/LES.2010.2081343, December 2010.

M. Sabry, A. K. Coskun, D. Atienza, T. Simunic, T. Brunschwiler, “Energy-Efficient Multi-Objective Thermal Control for Liquid-Cooled 3D Stacked Architectures”, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems (T-CAD), IEEE Press, November 2011, accepted.

F. Alfieri, M.K. Tiwari, I. Zinovik, D. Poulikakos, T. Brunschwiler and B. Michel, “3D integrated water cooling of a composite multilayer stack of chips”, Journal of Heat Transfer, accepted.

N. Borhani, B. Agostini, J.R. Thome, “A novel time strip flow visualisation technique for investigation of intermittent dewetting and dryout in elongated bubble flow in a microchannel evaporator,” International Journal of Heat and Mass Transfer 53, 4809-4818, 2010.

A.K. Coskun, J.L. Ayala, D. Atienza, T. Simunic, “Thermal Modeling and Management of Liquid-Cooled 3D Stacked Architectures”, in the book “VLSI-SOC: Design Methodologies for 2D/3D SoC and SiP”, Springer, Dordrecht/London/Boston, Editors: Jurgen Becker and Ricardo Reis, 2010, accepted.

P.G. Del Valle, D. Atienza, “Emulation-based transient thermal modeling of 2D/3D systems-on-chip with active cooling”, Elsevier Microelectronics Journal, ISSN: 0026-2692, 2010, accepted.

M. Hu, J. V. Goicochea, B. Michel, D. Poulikakos, “Water Nanoconfinement Induced Thermal Enhancement at Hydrophilic Quartz Interfaces”, Nano Letters 10, 279-285, 2010.

M. Hu, J. V. Goicochea, B. Michel, D. Poulikakos, “Thermal Rectification at Water Functionalized Silica Interfaces”, Applied Physics Letters 95, 151903, 2009.

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GreenPowerConnecting renewable energy to green mobility using hydrogen as energy carrier under the Belenos Clean Power initiative

PrinciPal investigator

Prof. Jan-Anders Månson, EPFL

co-aPPlicants

Dr. Lorenz Gubler, PsI

Dr. Emmanuel Onillon, CsEM

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GreenPowerCONNECTING RENEWABLE ENERGY TO GREEN MOBILITY usING HYDROGEN As

ENERGY CARRIER uNDER THE BELENOs CLEAN POWER INITIATIvE

GoalsAn environmentally friendly transportation system is of paramount importance for the decrease of emission of greenhouse gases to the environment. Belenos Clean Power (BCP) has been created as a Holding company whose aim is to accelerate the necessary revolution in clean energy production and consumption using solar energy, converting and storing it in the form of hydrogen and oxygen for mobility and other purposes. For the first time at national level, this initiative is considering green mobility as a part of the entire energy chain: it will give the impetus to accelerate and accumulate the know-how in R&D and production by associating creativity in new and existing resources in the several areas concerning clean energy.

The principle is to use solar energy, collected on home roofs, which is then used to electrolyze water in order to produce hydrogen and oxygen. These gases are compressed and stored locally to match the gap between supply and demand. Hydrogen and oxygen are filled in adhoc car reservoirs, and subsequently transposed to electricity for fuel cell driven cars. Such a demonstrator system can already be built today: Belenos team succeeded recently to develop H2-O2 fuel cell system and to integrate it in an appropriate vehicle and an electric boat. The vehicle will be tested for at least one year on the Swiss roads while the boat is navigating gor tests on Neuchatel Lake. However, the economic viability of the project depends on disruptive innovation based upon our capacity to face and resolve very demanding scientific and technical challenges in the years to follow. One of the main issues in this coherent effort is the optimization of the hydrogen production and usage chain. Several major steps, both in science and engineering, are needed to achieve the commercial exploitation of the overall concept.

As part of the developments on-going within Belenos, an issue is the development of adequate membranes for the fuel cells. In this project, the membrane will be based on new materials to enable a cost effective application in an H2-O2 fuel cell. These new membranes will be optimized for cost as well as for mechanical and chemical stability. Another issue addressed in this project is the safety related to hydrogen and oxygen storage in a car or at home: new appropriate materials will be developed to guarantee the gas storage system. The project will also seek to design, simulate and set up a unit managing gas flows, throughout the system components as well as the required communication system.

Main concept: Global decentralized production of hydrogen and oxygen coupled to renewable energy sources solar cells home-based electrolyser storage unit fuel cell by making fuel production at home possible and competitive

KEY UNDERLYING ISSUES

Electrolyser

Home ControlDirect Use

Photovoltaic

O2H2

Fuel Cell

• Adequate membranes for the fuel cells: Based on commodity polymer materials lower cost and longer life-time Optimized for mechanical & chemical stability + performance • Safe high pressure gas (H2 / O2) storage system Using new microscopic composite lining • Design, simulation & setting up of unit controlling gas flows (production + storage + usage) • Communication system

Role of federator, between new developments and specific elements (gas sensors, etc.) addressed in other projects.

Federating line: overall «Belenos Clean Power» concept for green mobility powered by sun energy + strong industrial & academic motivation

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ContextThe combined competence of polymer chemistry at PSI and materials analysis at EPFL is original and leads to unique findings enabling improved proton-exchange membranes (PEM) materials. The key asset of radiation grafted membranes produced at PSI over other types of partially fluorinated or hydrocarbon polymers for fuel cells, such as polyarylene membranes or polymer blends, is the lack of a film forming process combined with the use of low cost materials and the possibility to adjust membrane parameters (ion exchange capacity, water uptake, flexibility) in a wide range. In addition, numerous studies report the influence of irradiation, grafting, sulfonation and crosslinking on crystallinity, thermal degradation and melting behavior of PEM. However there is a general lack of data on the durability and thermo-mechanical stability of these hygrothermal sensitive materials. Such information is key to develop novel PEM with high operational stability.

The collaboration between CSEM (XRD analysis) and EPFL (composite processing, gas-barrier analysis, piezoelectric analysis) enables for the first time to determine the role of thermo-mechanical cycles and inorganic phases on crystalline structure and resulting gas-barrier and piezoelectric properties of PVDF-based composites. While the structure of the ferroelectric β-phase of PVDF has been extensively investigated, no precise study exists for the crystal structures of the P(VDF-TrFE) copolymers apart from a neutron diffraction analysis. This study confirms that the random substitution of H (Van der Waals radius of 0.12 nm) by F (0.13 nm) introduces little perturbation in the chain structure. However this substitution has a large influence on the Curie temperature, which suggests a noticeable change of the structure and the present project will bring new information to elucidate this issue. In addition, no study exists on the gas barrier properties of PVDF-based materials.

Hydrogen storage vessels are commonly made by reinforcing a metallic vessel using the well-known carbon filament winding process. Manufacture is time consuming and metals present a risk of H2 embrittlement. Alternative polymer liners were recently developed (5 mm thick polyethylene by Quantum Technology and polyamide by CEA/PSA with rotomolded polyurethane). Composite process technologies are also considered including fast resin transfer molding which also allows a finer tuning of carbon fiber braid architectures. The GreenPower project combines for the first time a self-sensing liner with a cost-effective RTM production process.

Regarding the control station, existing photovoltaic (PV) management systems are limited to monitoring of PV installations. Several systems do exist on the market, showing the production of photovoltaic electricity, installation temperature and may eventually announce mal-functioning of the installation. Some optimizations were performed at district level. A two stage (one day ahead and intra-day scheduling) was proposed. Optimization of renewable energy for green mobility can be found in some projects. The GreenPower project considers the house and associated hydrogen car as a system and develops adaptive prediction of energy production, consumption and storage capability. Advanced signal processing methods and optimization techniques are applied to the energy domain so as to optimize at best the energy flux between consumption and production. Moreover, health monitoring of the installation, including the car fuel cell and hydrogen storage is included in the management system, bringing novelty in such a system.

ResultsThe following main scientific results were recently obtained:

- Production and comprehensive mechanical and electrical analysis of piezo electric composites based on polyvinylidene tri-fluoroethylene copolymers P(VDF-TrFE) and up to 60 %vol of BaTiO3.

- Comprehensive analysis of the influence of thermo-mechanical treatments on the development of crystalline phases and piezoelectric properties of PVDF and P(VDF-TrFE) (EPFL-CSEM collaboration).

- Production of crosslinked proton-exchange membranes (PEM) based on grafted ethylene tetrafluoroethylene (ETFE), with superior durability compared to commercial PEM and identification and modeling of a moisture-induced viscoelastic transition in these membranes.

- Development of an energy fluxes management system, optimizing the use of photovoltaic electricity based on the user’s needs (domestic and mobility). The necessary simulation environment, prediction and optimization algorithms were developed, as well as the necessary control hardware (control station).

In particular, regarding the piezoelectric gas barrier liner, the collaboration work between EPFL and CSEM on P(VDF-TrFE) copolymer was instrumental in elucidating the formation of the crystalline polar β-phase (which controls the piezoelectric response) without complex mechanical stretching as required for PVDF homopolymer. Annealing post-treatments at higher temperature enhanced the proportion of β-phase up to 95% as proved by a combination of advanced XRD and thermal analyses. The resulting piezoelectric coefficient d33 was also improved, which should be useful to increase the sensitivity of the piezoelectric gas-barrier liner to the pressure state and therefore the safety of the hydrogen composite vessel.

Concerning the photovoltaic user’s interface, the Greenpower project allowed the partners to show the feasibility of optimization of energy fluxes based on adaptive and predictive methods, as well as on-line fuel cell monitoring. Hardware, relying on commercial solution is currently used to validate the proposed approach.

A joint Belenos-EPFL international patent application on the piezo-liner concept entitled ‘Self-Monitoring Composite Vessel for High Pressure Media Storage’ was submitted on Feb. 24, 2010.

Two joint Belenos-CSEM European patent applications on the energy flow management system were submitted on August 17 and November 28, 2011.

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PublicationsH. Ben youcef, L. Gubler, A. Foelske-Schmitz, G.G. Scherer, ‘Improvement of homogeneity and interfacial properties of radiation grafted membranes for fuel cells using diisopropenylbenzene crosslinker’ J. Membr. Sci. 381, 102– 109 (2011).

S. Balog, U. Gasser, K. Mortensen, H. Ben youcef, L. Gubler, G.G. Scherer, ‘Nano-scale morphology in graft copolymer proton-exchange membranes cross-linked with DIPB’, J. Membr. Sci. 381, 50-59 (2011).

H. Ben youcef, S. AlkanGürsel, A. Buisson, L. Gubler, A. Wokaun, G. G. Scherer, Influence of Radiation-Induced Grafting Process on Mechanical Properties of ETFE-Based Membranes for Fuel Cells, Fuel Cells 10 401-410 (2010).

L. Gubler , G. G. Scherer, Trends for fuel cell membrane development, Desalination 250, 1034–1037 (2010).

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i-IronICimplantable/wearable system for on-line monitoring of human metabolic conditions

PrinciPal investigator

Prof. Giovanni De Micheli, EPFL

co-aPPlicants

Dr. sandro Carrara, EPFL

Dr. Catherine Dehollain, EPFL

Dr. Fabio Grassi, IRB

Prof. Qiuting Huang, ETHZ

Prof. Yusuf Leblebici, EPFL

Dr. Linda Thoeny-Meyer, EMPA

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i-IronICIMPLANTABLE/WEARABLE sYsTEM FOR ON-LINE MONITORING OF HuMAN METABOLIC CONDITIONs

GoalsHuman metabolism telemetry requires accurate and frequent monitoring of the molecular response of living tissues. On-line monitoring of patients with specific physiological conditions (e.g., heart, cardiovascular, cancer diseases) is a key factor to provide better, more rationale, effective and ultimately low-cost health care. This is also required in professional and recreational sportsmen training, as well as in chronic, elderly and/or disabled citizen care.

With the present state-of-the art, metabolism monitoring is a complex and expensive process, mainly because of the unavailability of accurate, fast and affordable sensing devices that can detect and quantify multiple compounds in parallel and several times per day. To date, medical systems available on the market for human telemetry are using wearable devices (accelerometers, heartbeat monitoring system, etc) but they do not measure molecular metabolites. The only available real-time, implantable/wearable systems for metabolic control are limited to glucose monitoring in diabetic patients. For other pathologies, molecules are monitored in daily hospital practice by means of blood sampling and off-line analysis. This requires large and expensive laboratory equipments.

This project develops research in the field of integrated smart biosensors for online metabolism analysis that significantly improves the quality and reliability of measurements in humans, with reduced analysis-time and costs. Targets are several metabolic compounds of interest in cardiovascular diseases as well as inflammatory diseases and personalized nutrition, such as lactate, cholesterol, glucose, ATP, arachidonic acid, bilirubin, and others.

The scientific goal of designing, fabricating and testing biosensors for human telemetry is embodied in the assembly of a demonstrator: a minimally-invasive implanted device will host the biosensors and related electronic and it will transmit the information to a wearable intelligent patch, communicating with a portable device (e.g., a mobile phone), which is finally in remote communication with the geographical network (hospital/medi-care-cabinet/home). The patch is inductively coupled to the implanted device, and provides wireless transmission of power and data.

Goal: Study an innovative • multi-metabolites • highly integrated • fully implantable • real-time monitoring system for human metabolism

Currently available wearable systems for health monitoring:no metabolites measurements! (only glucose monitoring for diabetic patients)

Many different molecules are crucial to monitor: • lactate • ATP • cholesterol

3 KEY DEVICES

Fully implantable sensors array for data acquisition

Wearable station for remote powering and signal processing

Remote station for data collection and storage

EXPECTED BREAKTHROUGHS

Fully implantable sensors system

Multi-panel sensors to sense several metabolites(lactate, cholesterol, ATP, etc.) in parallel, in realtime

New software algorithms for signal analysis

New CMOS design for the fully-implanted, complexand low-consumption electronics for sensing andremote powering

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ContextCurrent advanced sensor-systems for continuous metabolite monitoring are mainly designed to cope with diabetes and rely on micro-tubing to extract blood or interstitial-fluids from the body. The measure is usually done in a wearable station on a belt. The major objectives of the i-IronIC project are to integrate the sensing and data elaboration electronics into a single fully-implanted device to be located under the skin, in the interstitial tissue, and to provide biological information forwarded directly to a medical network. Moreover, i-IronIC goes beyond glucose sensing, and targets other molecules, such as lactate, glutamate, glucose, arachidonic acid, bilirubin, ATP, etc. Therefore, medical diagnosis would benefit from simultaneous multi-panel sensing.

A working assumption is that medical biosensing platforms have to be designed in a modular fashion to decrease fabrication costs and acceptability barriers. Thus we extend to biosensing the working design methodology for microelectronics called platform-based design. Our approach involves a library of components and compositional methods. Components include probes, sensors and sensor structures, analog, digital and RF blocks as well as micro antennas and inductive coupling devices. Selecting and tailoring these components to the specific medical goal is a primary research objective of this approach.

ResultsSensing targets: Active research addresses the use of probe proteins, such as oxidases of lactate, glutamate, glucose, cholesterol, and others. Other proteins such as Hexokinase, Laccase, and Cytochrome P450 are considered as well. Those proteins are kept from the biotechnology marker in order to evaluate the costs of the technology. Those proteins are obtained by proteins engineering as well in order to evaluate possible improvements on the side of biotech with special focus on improved specificity, protein stability, sensors time-life.

Sensor technology: Sensors are fabricated and tested with electrodes that are nano-structured with carbon nanotubes (CNTs) in order to obtain larger sensitivity and lower detection limits. The already fabricated sensors have shown linearity within the considered range of medical interest. Parallel sensing of various metabolites has been achieved by a multi-probe sensor array. The current working prototype senses only one metabolite at time and it may be programmed by changing the sensing element. A new multi-panel sensor to sense in parallel different metabolites has been designed, fabricated and it is now under testing in the lab. A 1.52 mm x 1.52 mm CMOS chip provides the front-end current amplification and the biasing voltages for the sensors.

Signal and power transmission: Inductive and RF coupling are the two considered approaches for transmitting power to the implanted sensor as well as to receive data from it. The two different approaches are working at different frequencies with different designs of the power management system and of the micro-antenna. In particular, multi-spiral coils with various geometries to transmit power in the few MHz range were developed. The intelligent patch for short-distances communication has been designed, realized, and tested. Power transmission up to 2 mW at a 25 mm distance through a 15 mm beef-steak has been obtained by using the inductive link. A low-power long-distance communications device has been designed and tested, too.

Biocompatibility: The i-IronIC team has designed a first multi-target implantable prototype (measuring only one metabolite at time) with a 10 mm diameter cylinder. The prototype was tested in vivo and in vitro. The prototype has been tested in animals, and checked for biocompatibility. The pro-inflammatory potential of different prototypes has been evaluated in vivo by monitoring adenosine triphosphate (ATP) and neutrophils infiltration in air pouches generated in the back of mice.

The second prototype will be housed in a 2.5 mm diameter cylinder with 15 mm height. This prototype will house a passive microstrip monitoring 5 metabolites within an area of 2.2 mm x 15 mm, in addition to a microchip for energy harvesting, signal amplification and transmission. A special biocompatible housing of the prototype is being co-developed with IMEC.

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PublicationsGiovanni De Micheli, S. Sara Ghoreishizadeh, Cristina Boero, Francesco Valgimigli, and Sandro Carrara, An Integrated Platform for Advanced Diagnostics, Conference Proceedings of the International Conference on Design, Automation, and Test in Europe, DATE-2011, Grenoble, 14-18 March, 2011.

Sandro Carrara, Léandre Bolomey, Cristina Boero, Andrea Cavallini, Eric Meurville, Giovanni De Micheli, Fabio Grassi, Tanja Rezzonico, Single-Metabolite Bio-Nano-Sensors and System for Remote Monitoring in Animal Model, IEEE Sensors 2011, conference proceedings, pp 716-719.

Marialaura Beltrandi, Alain Vachoux, Sandro Carrara,Yusuf Leblebici, Giovanni De Micheli, VHDL-AMS Model of an Electrochemical Cell to Design VLSI Bio-Chips, BioCAS 2011, San Diego, November 10-12, 2011, pp. 321-324.

S. Sara Ghoreishizadeh, Sandro Carrara, and Giovanni De Micheli, Circuit Design for Human Metabolites Biochip, BioCAS 2011, San Diego, USA, November 10-12, 2011.

Sara S. Ghoreishizadeh, Camilla Bay-Rossi, Sandro Carrara, Giovanni De Micheli, Nano-Sensor and Circuit design for Anti-cancer Drug detection, IEEE/NIH Conference LiSSA 2011, April 7-8, 2011, pp. 28-33.

Irene Taurino, Sandro Carrara, Mauro Giorcelli, Alberto Tagliaferro, Giovanni De Micheli, Electrochemical comparison of two different oriented multi-walled carbon nanotubes directly grown on Si-wafers toward potassium ferricyanide detection, Surface Science, 2011 in press.

Irene Taurino, Sandro Carrara, Mauro Giorcelli, Alberto Tagliaferro, Giovanni De Micheli, Comparing sensitivities of multiple oriented multi-walled carbon nanotubes on silicon wafer for electrochemical biochips, Sensors and Actuators B: Chemicals 160 (2011) 327–333.

Jacopo Olivo, Sandro Carrara, Giovanni De Micheli, Energy Harvesting and Remote Powering for Implantable Biosensors, IEEE Sensors Journal 11 (2011), 1573-1586 (Journal-Issue Cover-Page).

Jacopo Olivo, Sandro Carrara, Giovanni De Micheli: Biofuel Cells and Inductive Powering as Harvesting Techniques for Implantable Sensors, Science of Advanced Materials 3 (2011), 420-425.

Jacopo Olivo, Sandro Carrara, and Giovanni De Micheli, Modeling of Printed Spiral Inductors for Remote Powering of Implantable Biosensors, 5th International Symposium on Medical Information and Communication Technology (ISMICT 2011), Montreux, March 27-30, 2011, pp. 29-32.

Jacopo Olivo, Sandro Carrara, Giovanni De Micheli, Optimal Frequencies for Inductive Powering of Fully Implantable Biosensors for Chronic and Elderly Patients, IEEE Sensors 2010 Conference, Hawaii, November 1-4, 2010, pp. 99-103.

O. Kazanc, C. Dehollain, F. Maloberti, “Impedance-Matched Sensor-Tag Antenna Design Using Genetic Algorithm Optimization”, 5th International Symposium on Medical Information and Communication Technology (ISMICT), pp. 61-64, March 2011.

O. Kazanc, F. Mazzilli, N. Joehl, F. Maloberti, C. Dehollain, "Miniaturized Antenna and Integrated Rectifier Co-Design for Remote Powering of Implantable Sensor Systems", accepted for presentation in January 2012, in Santa Clara (USA) at the IEEE RAWCON conference.

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IrSensintegrated sensing platform for gases and liquids in the near and mid-infrared range

PrinciPal investigator

Prof. Jérôme Faist, ETHZ

co-aPPlicants

Prof. Edoardo Charbon, EPFL

Dr. Lukas Emmenegger, EMPA

Prof. Hans Peter Herzig, EPFL

Dr. Daniel Hofstetter, uniNE

Dr. Alexandra Homsy, EPFL

Prof. Eli Kapon, EPFL

Prof. Herbert Looser, FHNW

Prof. Markus sigrist, ETHZ

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IrSensINTEGRATED sENsING PLATFORM FOR GAsEs AND LIQuIDs IN THE NEAR AND MID-INFRARED RANGE

Goals There is an increasing demand for sensitive, selective, fast and portable detectors for trace components in gases and liquids, e.g. due to increasing concerns about atmospheric pollutants, and a need for improved medical screening capabilities for early detection of diseases and drug abuse. In that context, the project IrSens aims at building a versatile platform based on optical spectroscopy in the near and midinfrared range. Indeed, techniques based on optical absorption offer the possibility to realize a non-invasive and highly sensitive detection platform. It allows to probe the vibrational frequencies of the targeted molecules – most of which are located in the near and mid-infrared range, and to obtain an unambiguous signature of the investigated gas or liquid.

The idea is to create a photonic sensor platform with high performance and reliability which will leverage on the new source, detector and interaction cell technologies to create a new sensor element with vastly improved performance and lowered cost. These improvements will be demonstrated further by the incorporation into two pilot applications, the first one aiming at the demonstration of sensing in the gas phase, the second one in the liquid phase.

The compact sensing platform for gases under development is based on multipath absorption cells with various compact semiconductor light source and detector types. Infrared absorption spectroscopy can be used to detect a wide variety of gases. To demonstrate its suitability for breath analysis, the first part of this project is focused on the detection of helicobacter pylori – a bacteria responsible for gastric ulcers – by means of isotopic ratio measurements in exhaled CO2.

The integrated sensing platform for liquids is based on waveguiding and surface measurement technologies and the same source and detector types as for the gas sensing. The idea is to couple the sources to an optical module where the liquid analyte will flow through a built-in microfluidic channel. This is intended to be used mainly in bio-medical applications with an emphasis on drugs and doping agents detection in human fluids: specifically, a first targeted demonstrative application for this sensor would be the cocaine detection in human saliva.

Sensing platform based on optical absorptionPrinciple: probing the vibrational frequencies of targeted molecules (near/mid-infrared range) unambiguous signature of the fluid investigated

• high sensitivity for both gases and liquids• low price• low power consumption

Human breath analysisQCLs as powerful light source in the mid-infrared

Detection of the helicobacter pylori with isotopic ratio measurements in exhaled CO2

OPTICAL SENSING IN THE GAS PHASE

Vertical Cavity Surface Emitting LaserQuantum Cascade LaserQuantum Cascade Detector

Semiconductor opticalsources & detectors

OPTICAL SENSING IN THE LIQUID PHASEMulti wavelength semiconductor laser source(mid-infrared QCLs – near-infrared VCSELs)

• high sensitivity • small sample volume needed

Ideal for bio-medical applications

Detection of drugs & doping agents in human fluids

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ContextCommercially available solutions for portable gas detection are based on electrochemical or micromechanical processes, giving small sensitivity, or on optical absorption in gas cells, but their portability and ruggedness suffers from voluminous optical benches, especially in the case of FTIR systems, as explained in the project proposal. There exist other research programs on similar projects for optical sensors, like MIRTHE (NSF, USA), DARPA Center for Optofluidic Integration, or NRC ICT Sector (NRC-CNRC, Canada), and individual research groups working on gas or microfluidic sensing.

This project is particular as it aims at building two prototype systems allowing to work in near and mid infrared, with fluids as well as gases, but still portable and small with low power demands acceptable for remote monitoring applications. The detection schemes are deliberately kept simple (absorption, photoacoustics), to be independent from the peculiarities of target species (excluding Faraday rotation, etc). It therefore combines several of the targets of other programs, making use of technological advantages of different wavelength ranges. To achieve this, IrSens combines the expertise of several groups of top Swiss research institutes in a highly interdisciplinary network. To our knowledge, this is the only project using just III-V material based source and detector systems, and represents the only integrated waveguide based liquid measurement approach.

In some areas (sources, detectors, and gas sensing system), best performance compared to state of the art has already been achieved.

Results The second generation of near-infrared and mid-infrared sources has been produced, partly showing world record performances with respect to low power consumption.

In the detector part of the project, the second generation of quantum cascade detectors has been produced and tested, resulting now in devices available for both the 4 and 6 μm range; in addition, a custom made quantum cascade detector preamplifier has been designed, built and tested superior to commercially available devices. The new avalanche photodiode (APD) NIR detector design has been finished, and production and testing of the building blocks has started.

For the gas sensing part, a cylindrical gas cell based on six mirrors has been produced and tested in combination with the improved quantum cascade laser, already showing superior precision to comparable commercially available systems.

In the liquid sensing part, the liquid mixing and the waveguide subsystems have been realized and tested. The benchmark measurement system is being completed with quantum cascade laser and quantum cascade detector units. Cocaine in saliva already could be detected at concentrations reported in the literature for field measurements.

PublicationsA. Manninen, B. Tuzson, H. Looser, Y. Bonetti, L. Emmenegger, "Versatile multipass cell for trace gas analysis based on quantum cascade laser", Applied Physics B, special issue TDLS 2011 (accepted for publication).

D. Hofstetter, J. Di Francesco, L. Hvozdara, H.-P. Herzig, M. Beck, “CO2 isotope sensor using a broadband infrared source, a spectrally narrow 4.4 μm quantum cascade detector, and a Fourier spectrometer”, Applied Physics B 103 (4), 967, 2011.

Ph. Wägli, A. Homsy, N.F. de Rooij; “Norland optical adhesive (NOA81) microchannels with adjustable wetting behavior and high chemical resistance against a range of mid-infrared-transparent organic solvents”, Sensors and Actuators B 156, 994-1001, 2011.

K.M.-C. Hans, S. Müller, M.W. Sigrist; “Infrared Attenuated Total Reflection (IR-ATR) Spectroscopy for Detecting Drugs in Human Saliva”, Drug Testing and Analysis (accepted for publication).

A. Sirbu, V. Iakovelv, A. Mereuta, A. Caliman, G. Suruceanu and E. Kapon, “Wafer-fused heterostructures: application to vertical cavity surface-emitting lasers emitting in the 1310 nm band”; Semicond. Sci. Technol. 26 (2011) 014016.

L. Mutter, B Dwir, A. Caliman, V. Iakovlev, A. Mereuta, A. Sirbu, E. Kapon, “Intra-cavity patterning for mode control in 1.3μm coupled VCSEL arrays”, Optics Express 19(6).

A. Sammak, M. Aminian, L. Qi, W. D. de Boer, E. Charbon, L.K. Nanver, “A CMOS Compatible Ge-on-Si APD Operating in Proportional and Geiger Modes at Infrared Wavelengths”, International Electron Device Meeting (IEDM), Washington, DC, Dec. 2011 (accepted for publication).

Ph. Wägli, A. Homsy, N.F. de Rooij, “Norland Optical Adhesive (NOA81) Microchannels with Adjustable Surface Properties and High Chemical Resistance Against IR-Transparent Organic Solvents”, Oral presentation at Eurosensors XXIV conference, September 5 - 8, 2010, Linz, Austria (extended abstract published in Procedia Engineering 2010).

F.R. Giorgetta, E. Baumann, M. Graf, D. Hofstetter, Q. Yang. C. Manz, K. Köhler, H.E. Beere, D.A. Ritchie, E. Linfield, G. Davies, Y. Fedoryshyn, H. Jäckel, M. Fischer, J. Faist, and D. Hofstetter, “Quantum Cascade Detectors”, Journal of Quantum Electronics 45, no. 8, pp. 1029-1042, 2009.

D. Hofstetter, F.R. Giorgetta, E. Baumann, Q. Yang, C. Manz, and K. Köhler, “Mid-infrared quantum cascade detectors for applications in spectroscopy and pyrometry”, Applied Physics B 100, no. 2, pp. 313-320, 2010.

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Add-on: IR-N-ox MID-INFRARED MuLTI-LAsER MODuLE FOR DETECTION OF NxOY sPECIEs

PrinciPal investigator Prof. Jérôme Faist, ETHZco-aPPlicants Dr. Lukas Emmenegger, EMPA Prof. Hans Peter Herzig, EPFL

iR-N-ox is an add-on project to Nano-Tera – irSens carried out by a consortium of three academic partners (EPFL, ETHZ, and EMPA) and one industrial partner (Alpes Lasers S.A.). it seeks the realization of a module, comprising three quantum cascade lasers, emitting at three different wavelengths. The module allows for independent wavelength stabilization of each laser, and the common exit aperture is smaller than 40 microns. in addition, an alternative approach using multiple-wavelength lasers based on current broad spectral gain active material will be pursued, independent of waveguiding techniques. The laser module is dedicated to gas spectroscopy. it will allow the analysis of all gaseous species with absorption features in the frequency range of the lasers using a single optical path. The performance of the module will be proven employing a high-end spectrometer designed for measurements down to the ppt concentration level. The lasers will be selected such that they allow the simultaneous detection of N2o, No and No2 (or two out of the three species for the alternative approach), since there is currently no satisfactory analytic method for selective, sensitive and real time measurements of these gases. Moreover, there are numerous industrial and environmental applications where such measurements are a prerequisite to understand and control the underlying processes. in addition to irSens, iR-N-ox has strong synergies with openSense - a NanoTera project focused on open sensor networks for air quality monitoring. To take advantage of these common interests, the laser module will also be coupled to the gas sensing platform currently developed within irSens, and assessed with respect to the potential deployment as a sensor within openSense.

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ISyPeMintelligent integrated systems for personalized medicine

PrinciPal investigator

Prof. Carlotta Guiducci, EPFL

co-aPPlicants

Dr. Thierry Buclin, CHuv

Prof. Giovanni De Micheli, EPFL

Prof. Christian Enz, CsEM

Prof. Carlos-Andrés Pena-Reyes,

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ISyPeMINTELLIGENT INTEGRATED sYsTEMs FOR PERsONALIZED MEDICINE

GoalsMedical progress is increasingly improving the survival rate and life quality of patients affected by serious, life-threatening conditions, such as HIV infection, disseminated cancers or vital organ failure. These achievements rely significantly on new radical improvements of drug regimens and therapeutic protocols. Newly adopted treatments for such diseases require the daily administration of highly active therapies in the long-term.

The huge variability range in drugs response poses strong limits and severe problems in drug treatment definition. The largest part of variability in drug response (roughly 80%) resides in the pharmacokinetic phase, i.e. in dose-concentration relationships. This project aims at providing advanced technologies for assessing drug response by measuring drug concentrations and relevant biomarkers. In particular, it aims at providing drug treatment optimization based on processing of statistical and personal data and to enable seamless monitoring and delivery by an ultra-low power integrated system. Thus it is the purpose of the project to advance the state-of-the-art in personalized medicine by creating new enabling technologies for drug monitoring and delivery control rooted in the combination of sensing, in situ data processing, short-range wireless communication and drug release control mechanisms. These new technologies, in combination with currently available medical devices (e.g., micropumps, micro-needles, etc.) can significantly improve medical care and reduce the related costs.

The research goes beyond the state-of-the-art because of the introduction of new sensing and delivering technologies, ultra-low power sensor interface and wireless communication integrated in a miniaturized remote-powered hardware platform with energy-efficient data processing and robust control software. Targeted application domains will be HIV infection, cancer diseases and post-transplant therapies, which are currently addressed by the research in pharmacokinetics carried out by our medical partner at CHUV.

The overall benefit of this research is bettering medical practice by enabling personalized medicine while reducing health care costs. This goal is achieved by a concerted effort in various disciplines that will be embodied in demonstrators and validated in the field in the framework of the project. The state-of-the-art will be advanced by providing an electronic-control dimension to drug treatment, based on novel analytical techniques and on safe and optimal dosing policies. Expected scientific breakthroughs include new integrated sensors for specific drugs and biomarkers, new drug delivery mechanisms via electronically-controlled silicon membranes and a formal design methodology for provably correct and safe electronic drug delivery.

Medical treatments often require daily drug administration of highly active therapies over long-term periods

Goal here: Provide advanced technologies to…

• assess drug response by measuring drug concentration & relevant biomarkers • provide drug treatment optimisation based on statistical & personal data • enable seamless monitoring & delivery an ultralow-power integrated system

Exploration of new sensor technologies, hardware/software data processing, drug release mechanisms based on silicon membranes

… combined with existing medical devices better & cheaper medical care!

Provide an electronic-control dimension to drug treatment, based on real-time sensing and safe & optimal dosing policies

• HIV infection• cancer diseases• post transplant therapies

EXPECTED BREAKTHROUGHS• New integrated sensors for specific drugs and biomarkers• New drug delivery mechanisms via electronically-controlled silicon membranes• Formal design methodology for provably correct and safe electronic drug delivery

TARGETED APPLICATION DOMAINS

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ContextDrug concentration monitoring currently requires a complicated interplay between medical, laboratory and pharmacokinetic competences. It is relatively underdeveloped in the healthcare systems of most Western countries. Switzerland is thus in an ideal position to foster further developments towards improved and facilitated use of this important aspect of personalized patient management.

The ISyPeM project addresses the development of a set of technologies for drug sensing, drug dosing and drug prediction to be employed singularly or integrated according to the specific application.

During the last three decades the computer interpretation of medical guidelines and protocols has drawn lots of attention from the researchers of various domains aiming to improve the quality of medical services. To allow the personalization of the drug dosing for each critical patient, the consortium is working on the development of a point-of-care system for Therapeutic Drug Monitoring (TDM) practice. The system would be able to analyze blood samples and to measure the drug concentration. The electronics for point-of-care sensing has been designed by CSEM in order to meet required performance in terms of sensitivity and flexibility. The same platform would provide drug dosing indications thanks to the integration of algorithm for dose prediction and patient’s records.

Regarding automated delivery, the consortium is focusing on one side on the safety issues related to automation of drug indications and delivery procedures, on the other side, on electrically-driven integrable membranes for controlled delivery of drugs. In particular, an automated drug delivery system requires a level of safety that is at least the same as the one provided by a regular medical operator. The consortium has addressed this challenge by the method of formal modeling that would allow protocol formal verification.

ResultsThe consortium is fostering crucial improvements in several related scientific and technological fields:

Monitoring of critical drug agents: The medical needs to concentration monitoring have been reviewed, and two drugs have been chosen as demonstrators for the development of novel monitoring tools, namely efavirenz and imatinib. In parallel, efforts are devoted to sensitize the prescribers to the importance of monitoring for critical drug agents. Theoretical elaborations are pursued regarding the best approaches to be used to summarize suitable pharmacokinetic-pharmacodynamic data from the literature, extract and combine their population parameters, and design rational strategies for the interpretation of the patients’ measurement results and their translation into appropriate therapeutic decisions in term of dosage adjustment. An important work of validation of a Bayesian Maximum A Posteriori (MAP) strategy to predict patient’s exposure at a standard time has been completed, based on real-life observations (series of patients having provided both random time and actual trough samples).

Molecular probes for small drugs: In order to allow a portable alternative for the analysis of blood samples containing small drug, the Laboratory of Life Sciences Electronics at EPFL identified alternative techniques with respect to mass spectrometry that would allow the surface capturing on drug in an array format. Moreover, the team introduced the use of specific and robust molecular probes called Aptamers. Standard SELEX methods for Aptamers usually select for oligonucleotides able to bind to an immobilized target. Beacon Aptamers SELEX instead selects oligonucleotides that bind the target while immobilized on a surface, and change conformation in response to the binding. However, available BA SELEX is based on RNA (poor stability and demanding chemical synthesis), therefore a BA SELEX is being developped on DNA.

Disposable sensing layers: In order to lower the costs of the sensors for point-of-care drug-concentration measurements, the Laboratory of Life Sciences Electronics at EPFL is developing a process to provide a disposable sensing layer on the top of silicon chips.

Sensor interface: Traditional biomedical sensor interfaces employ techniques like chopper stabilization, auto-zeroing in the front-end for reducing the effects of flicker noise and then use a sampling based A/D converter for analog-to-digital conversion. The architecture of the proposed asynchronous biomedical sensor interface is based on novel techniques like noise canceling combined with chopper stabilization and clock-less A/D conversion.

Drug delivery: The most innovative aspects of CSEM approach to the development of silicon membranes for drug delivery is the ability to produce homogeneous membranes at larges scales and to control the pore size and density in a facile manner. In other words, they can tune the membranes properties according to the envisioned application.

The consortium (Laboratory of Integrated Systems and CHUV) is investigating the machine-learning approach. SVM algorithm is a powerful approach used to separate highly intertwined data. In initial classification problems solved by an SVM algorithm maps the input data to a binary output. Later the SVM approach has been extended with regression analysis used to predict real numbers. In order to further improve the accuracy of the prediction, two example-based SVM approaches were proposed to pre-select the training samples for modeling: uniform and discriminatory strategies. Compared with the traditional Pharmacokinetic method, this methods surpass it by 44.3% in predicting the concentration within a 200 (μg/L) accuracy range.

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PublicationsT. Buclin, N. Widmer, J. Biollaz, L.A. Decosterd. “Who is in charge of assessing therapeutic drug monitoring? The case of imatinib”. Lancet Oncol. 12(1), 9-11, 2011.

A. Fayet Mello, T. Buclin, L.A. Decosterd, C. Delhumeau, J. di Iulio, A. Fleurent, M.P. Schneider, M. Cavassini, A. Telenti, B, Hirschel, A. Calmy. “Successful efavirenz dose reduction guided by therapeutic drug monitoring”, Antivir Ther. 16(2), 189-97, 2011.

V. Gotta, N. Widmer, M. Montemurro, S. Leyvraz, A. Haouala, L.A. Decosterd, C. Csajka, T. Buclin. “Therapeutic drug monitoring of imatinib: Bayesian and alternative methods to predict trough levels”, Clin Pharmacokin. 2011 (accepted; in press).

Thierry Buclin, Verena Gotta, Aline Fuchs, Nicolas Widmer, Jeffrey Aronson. An agenda for UK clinical pharmacology: Monitoring drug therapy. Brit J Clin Pharmacol 2012 (in press).

D. Ruffieux, M. Contaldo, J. Chabloz, and C. Enz, "Ultra Low Power and Miniaturized MEMS-based Radio for BAN and WSN Applications," Proc. of the European Solid-State Circ. Conf. (ESSCIRC), pp. 71-80, Sept. 2010.

D. Ruffieux, M. Contaldo and C. Enz, “MEMS-based All-digital Frequency Synthesis for Ultralow-Power Radio for WBAN and WSN Applications,” IEEE Int. Symp. on Circuits and Syst. (ISCAS), pp. 157-160, May 2011.

A. Heragu, D. Ruffieux, J. Chabloz, and C. Enz, "A MEMS-based 2.4 GHz Sub-sampling RF Front-end for Advanced Healthcare Applications," Proc. of the IEEE Int. Symp. on RF Integration Technology, Nov. 2011 (Invited Paper), accepted.

Wenqi You, Nicolas Widmer, Giovanni De Micheli, ‘Example-based Support Vector Machine for Drug Concentration Analysis’, 33rd IEEE EMBS, USA, August 2011, pp.153-157.

Wenqi You, Nicolas Widmer, Giovanni De Micheli, ‘Personalized Modeling for Drug Concentration Prediction Using Support Vector Machine’, 4th IEEE BMEI, October 2011 (to appear).

Y. Temiz, E. Accastelli Y. Leblebici and C. Guiducci, "Robust Microelectrodes Developed for Improved Stability in Electrochemical Characterization of Biomolecular Layers," Proc. IEEE Sensors, 2010.

C. Guiducci, Y. Temiz, Y. Leblebici, E. Accastelli, A. Ferretti, G. Cappi, E. Bianchi, "Integrating Bio-sensing Functions on CMOS Chips," Proc. of Asia Pacific Conference on Circuits and Systems (APCCAS 2010), accepted.

A. Heragu, V. Balasubramanian and C. Enz, “A Multiband Concurrent Sampling based RF Front End for Biotelemetry Applications,” IEEE Int. Symp. on Circuits and Syst. (ISCAS), pp. 2948-2951, June 2010.

V. Balasubramanian, A. Heragu, and C. Enz, “Analysis of Ultralow-Power Asynchronous ADCs,” IEEE Int. Symp. on Circuits and Syst. (ISCAS), pp. 3593-3596, June 2010.

Temiz, Y.; Kilchenmann, S.; Leblebici, Y.; Guiducci, C.; "3D integration technology for lab-on-a-chip applications," Electronics Letters 47, no.26, pp.S22-S24, December 22, 2011.

Add-on: TWPeMTOWARDs WIDEsPREAD PERsONALIZED MEDICINE

PrinciPal investigator Prof. Carlotta Guiducci, EPfLco-aPPlicants Dr. Thierry Buclin, CHuV Prof. Giovanni De Micheli, EPfL Prof. Christian Enz, CSEM Prof. Carlos-Andrés Pena-Reyes, HES-So

Since the elaboration of the project, a potential “cultural” barrier was identified among healthcare providers towards the acceptance of a miniaturized device able to measure drug concentration or biomarker: this is due to the fact that therapeutic monitoring almost exclusively relies on empirical procedures in the medical community and that presently, the drug concentration measurement in patients sample is performed only in dedicated medical laboratories, working rather far from clinical practice.

However, a cultural change is certainly about to occur among drug prescribers regarding therapeutic drug concentration monitoring, as several critical elements are now available, just to name a few: pharmacokinetic characterization of new drug agents has become mandatory from registration agencies during the last two decades, population pharmacokinetic modeling has progressed and is increasingly used in clinical research, the need for dosage individualization is more and more widely acknowledged among experts, especially regarding new critical therapies.

Novel computer tools might perfectly enjoy success among medicinal drug prescribers, provided that they are easy to operate, user-friendly, multiplatform, versatile regarding drug choices, and free to use. The aim of this project is thus to rapidly develop software and hardware easy-to-use tools and to disseminate them among the community of healthcare providers.

With such a vision, the Division of Clinical Pharmacology and Toxicology at CHuV and the HEiG-VD developed the Ezekiel software whose goal is to provide an ergonomic platform that will help the medical doctors with the monitoring of drug concentration, and with possible drug posology prediction. The first on line release of the software has already been made available to all medical doctors and pharmacologists interested in such monitoring.

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LiveSenseCell-based sensing microsystem

PrinciPal investigator

Prof. Philippe Renaud, EPFL

co-aPPlicants

Prof. Nico de Rooij, EPFL

Prof. Martial Geiser, HEssO

Prof. Hubert Girault, EPFL

Dr. Martha Liley, CsEM

Dr. Michael Riediker, IsT

Prof. Jan van der Meer, uNIL

Prof. viola vogel, ETHZ

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LiveSenseCELL-BAsED sENsING MICROsYsTEM

GoalsA big challenge in environmental monitoring is to dispose of a base of autonomous remote nodes that are capable of locally collecting samples and sending biologically and chemically relevant information through a communication network. Analytical chemical methods commonly used are mostly based on sophisticated instrumentation which does not scale to miniature systems for deployment as field sensors. The use of biological entities such as cell lines or micro-organisms as the basis for assay methodologies has been well developed, and research has demonstrated their applicability for monitoring the environment for bioactive or toxic compounds. The response of cell-based sensors is related to a metabolic pathway and thus can be relevant to effects expected for human beings. In many cases, the response of cells and cell-based sensors is extremely sensitive. While the concept of cell-based biosensors has been researched for several years, their implementation is restricted to a few commercial applications that are not deployable as autonomous sensors.

This project addresses the need to improve the environmental monitoring of the many chemical and biological compounds that are affecting our biosphere and eventually human health. The idea is to use living cells as biosensors and to monitor them in a microfluidic bioreactor equipped with microsensors. Living cells are the most natural biosensors, since they integrate the biological effects of the compound mixtures and respond by metabolic or phenotypic changes that are relevant to potential effects in the human body. The projects aims at the realization of a complete autonomous microsystem that would include a cell culture microbioreactor, secondary sensors to measure cell response and monitor the microbioreactor process, a signal processing control unit and a wireless communication unit to link the microsystem to a sensor network.

The research is based on known cell models selected in two cell types: bacteria – used because there is already a wide experience on bacterial bioreporters and they are rather easy to culture – and eukaryotic cells – because their metabolic response to toxicants is more similar to reaction pathways in the human body. The microbioreactor will be integrated into a functional demonstrator for the deployment of a cell-based sensor network monitoring water quality in a Swiss river.

The long term goal of this project is to set a precedent on the industrialization of cell-based sensors which can eventually impact other fields including the toxicological screening of new drugs and chemical compounds without using animal models, large-scale studies of cell development and bioreactors for tissue engineering.

Environmental monitoring – warning system for the health of a biotope

need a set of autonomous remote nodes able to locally collect samples and send information

Cell-based biosensors provide a biologically relevantresponse to toxic compounds and mixtures

Strong interactions between partner teams:

• study of the cell models• development of microbioreactor• secondary sensors to detect the cell response• integration of a demonstrator to be deployed in a river

canary usedas «biosensor»in coalmines

sampling Cells

nutrientsupply

bioreactor microsystem platform

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ContextMost existing cell-based biosensors consist of genetically modified microorganisms (e.g., bacteria) expressing a specific reporter gene in the presence of the chemical target, an activation that translates into the synthesis of a reporter protein that is finally measurable by secondary sensors (spectrometry, fluorometry or electrochemistry).

Eukaryotic cell lines have also been studied in cell-based biosensing. For example, the 3T3 fibroblast has been selected for toxicology screening applications to study the cytotoxicity and carcinogenic potential of chemicals. Changes affecting the junctions between cells can be easily evaluated using measurements of electrical impedance across the layer, which offers a sensitive and rapid response without the need for genetic engineering. Eukaryotic cell-based sensors can produce signals on different time scales.

Cell-based sensors which rely on gene induction and synthesis of reporter proteins usually respond in the range of 30 minutes to 2 hours. However, reactions that depend on opening or closing membrane channels e.g. Ca channels in B-lymphocytes can give responses to targeted pathogenic material within minutes. While the concept of cell-based biosensors has been researched for several years, its implementation is restricted to a few commercial applications, such as the MicroTox® assay that is based on natural bioluminescent bacteria that are no deployable as autonomous sensors.

This project differentiates from others by proposing an innovative fully autonomous cell biosensor that is based on metabolic sensing methods (e.g., viability, metabolic rates, natural enzyme production, contractility, etc.). The consortium integrates research teams covering all aspects of the problem: biology, biomaterials, chemistry, microtechnology, electrotechnics and signal processing. A group of industrial partners can also advise and provide samples.

ResultsThe cell models – genetically modified E. coli, HepG2/C3A (hepatocytes) as well as C2BBe1 (derived from a human epithelial colorectal adenocarcinoma) – have been defined. Their storage and culture protocols have been established and routinely used. Target analytes are identified and the sensitivity of the cell sensors to each of them is characterized.

The bioreactors (for bacterial cells, hepatocytes and epithelial cells) are functional and are now being integrated to the environmental sensing system. The module to automatically adjust the osmolality of the water sample before introducing it in the bioreactor is now also functional.

The secondary sensors: fluorescence, electrochemical, impedance, mechanical and trans-epithelial electrical resistance; are functional and characterized using the cell models.

The modular system to be used in actual environmental monitoring has been built according to specifications and validated by characterizing the relation between the fluorescence intensity and the concentration of arsenic in a sample. The basic remote control of this system using a smart phone has also been demonstrated.

Ongoing work is on the integration of the bioreactors in this system, development of the pre-treatment module for cell culture nutrients and on the module to extract the sample from the river.

Among significant facts related to the LiveSense project:

- The team has found a label-free way to distinguish healthy, sick and dead cells by taking into account the whole frequency spectrum for analysis. Thus, cellular changes can be sensed long before cellular death, offering a highly sensitive technique over conventional viability assays such as MTT assay. Such findings have found great interest from other researchers which lead to an invitation for a plenary talk at the Impedance-Based Cellular Assays Conference (IBCA) in Tegensburg, Germany in 2011.

- The German Helmholtz Society awarded the Erwin Schrödinger Prize 2010 for Interdisciplinary Research to Jan Roelof van der Meer, Hauke Harms and Mona Wells for their development of bacterial reporter assays to detect arsenicals in drinking water.

- Prof. Viola Vogel of ETHZ obtained an ERC Advanced Grant (2009 – 2014).

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PublicationsR. Kumari, R. Tecon, S. Beggah, R. Rutler, J. S. Arey, J R. van der Meer, Development of bioreporter assays for the detection of bioavailability of long-chain alkanes based on the marine bacterium Alcanivorax borkumensis strain SK2, Environmental Microbiology doi:10.1111/j.1462-2920.2011.02552.x (2011).

N. Buffi, D. Merulla, J. Beutier, F. Barbaud, S. Beggah, H. van Lintel, P. Renaud, J R. van der Meer, Development of a microfluidics biosensor for agarose-bead immobilized Escherichia coli bioreporter cells for arsenite detection in aqueous samples. Lab Chip 11, 2369-2377 (2011).

N. Buffi, D. Merulla, J. Beutier, F. Barbaud, S. Beggah, H. van Lintel, P. Renaud, J R. van der Meer, Miniaturized bacterial biosensor system for arsenic detection holds great promise for making integrated measurement device. Bioengineered Bugs 2, 5, September/October (2011, Addendum).

R. Meissner, B. Eker, H. Kasi, A. Bertsch, P. Renaud. Distinguishing drug-induced minor morphological changes from major cellular damage via label-free impedimetric toxicity screening. Lab Chip 11, 2352 – 2361 (2011).

Kunze, R. Meissner, S. Brando, and P. Renaud. Co-pathological connected primary neurons in a microfluidic device for Alzheimer studies. Biotechnology and Bioengineering 108 (9), 2241-2245 (2011).

H. Kasi, R. Meissner, A. Babalian, H. van Lintel, A. Bertsch, and P. Renaud. Direct localised measurement of electrical resistivity profile in rat and embryonic chick retinas using a microprobe. Journal of Electrical Bioimpedance 1, 84-92 (2010).

O. Frey, S. Talaei, P. D. van der Wal, M. Koudelka-Hep and N. F. de Rooij, Continuous-flow multi-analyte biosensor cartridge with controllable linear response range, Lab Chip 10, 2226-2234 (2010).

Van der Meer, J. R., Belkin, S. Where microbiology meets microengineering: design and applications of reporter bacteria, Nat Rev Microbiol 8, 511-522 (2010).

Tecon, R., Beggah, S., Czechowska, K., Sentchilo, V., Chronopoulou, P. M., McGenity, T. J., van der Meer, J. R., Development of a Multistrain Bacterial Bioreporter Platform for the Monitoring of Hydrocarbon Contaminants in Marine Envirionments. Environ Sci Technol 144, 1049-1055 (2010).

S. Talaei, O. Frey, S. Psoma, P. D. van der Wal and N. F. de Rooij, Smart SU-8 pillars implemented in a microfluidic bioreactor for continuous measurement of glucose, Procedia Engineering 5, 448–451 (2010).

S. Talaei, O. Frey, P. D. van der Wal, N. F. de Rooij and M. Koudelka-Hep, Hybrid microfluidic cartridge formed by irreversible bonding of SU-8 and PDMS for multi-layer flow applications, Procedia Chemistry 1, 381-384 (2009).

Kunze, R. Meissner, and P. Renaud. Neurite guidance through 3D hydrogel layers in a microfluidic environment, in Proceedings of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2010), volume 1, pp. 187-189 (2010).

J. Park, R. Meissner, o. ducoux, H. van Lintel, P. Renaud, and H. Fujita. A Ca2+ ion selective electrode biosensor in microfluidics to monitor hepatocytes activities, in Proceedings of the 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2010), volume 1, pp. 247-249, 2010.

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MIXSELVertical integration of ultrafast semiconductor lasers for wafer-scale mass production

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PrinciPal investigator

Prof. ursula Keller, ETHZ

co-aPPlicants

Prof. Eli Kapon, EPFL

Prof. Thomas südmeyer, uniNE

Prof. Bernd Witzigmann,

uni Kassel

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MIXSEL

vERTICAL INTEGRATION OF uLTRAFAsT sEMICONDuCTOR LAsERs FOR WAFER-sCALE MAss PRODuCTION

GoalsShort pulse laser sources have enabled many applications in science and technology. Numerous laboratory experiments have confirmed that they can significantly increase telecommunication data rates, improve computer interconnects, and optically clock in the future multicore microprocessors. New applications in metrology, supercontinuum generation and life sciences with two-photon microscopy and optical coherence tomography only work with ultrashort pulses, but have relied on bulky and complex ultrafast solid-state lasers. However, users in health care and life sciences generally would rather get the short pulses without any further overhead and with a simple turn-on-off switch. It is therefore essential for them to have access to compact, easy-to-use and inexpensive ultrafast lasers. Recent developments in novel semiconductor lasers have the potential to reduce the complexity of ultrafast lasers.

Semiconductor lasers are ideally suited for mass production and widespread applications, because they are based on a wafer-scale technology with a high level of integration. Not surprisingly, the first lasers entering virtually every household were semiconductor lasers in compact disk players. A new ultrafast semiconductor laser concept has been introduced by Prof. Keller, which is power scalable, suitable for pulse repetition rate scaling in the 10 to 100 GHz regime, supports both optical and electrical pumping and allows for wafer-scale fabrication. This class of devices is referred to as the modelocked integrated external-cavity surface emitting laser (MIXSEL). The next step towards even lower-cost and more compact ultrafast lasers will be electrical pumping with both pico- and femtosecond pulses. This would result in devices ideally suited for many applications such as telecommunications, optical clocking, frequency metrology, high resolution nonlinear multiphoton microscopy, optical coherence tomography, laser display – anywhere where the current ultrafast laser technology is considered to be too bulky or expensive.

The project aims to demonstrate optically and electrically pumped MIXSELs in both the pico- and femtosecond regime. Picosecond MIXSELs are ideally suited for clocking applications whereas femtosecond MIXSELs are required for continuum generation and many biomedical applications. For both cases, average powers above 100 mW with electrical pumping and above 500 mW with optical pumping should be reached, which represent significant advances of ultrafast MIXSELs.

Ultrashort pulse lasers: crucial for biomedical applications(optical coherence tomography, photo-ablation of biological tissues…)

But need for affordable, integrable femtosecond laser modules

MIXSEL: mode-locked integrated external-cavity surface emitting laserSo far: only low-power optically pumped and picosecond regime MIXSELs

Passive mode-locking requires saturable absorbers

Further development necessary:

For integration into MIXSELs and for femtosecond regime:exploration of quantum dot saturable absorbers

>500mW

Goal:

>100mW

Demonstrate optically & electrically pumped MIXSELsin the picosecond and the femtosecond regime

clockingapplications…

continuum generation,biomedical applications…

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ContextAt the ETH Zurich, all ultrafast OP-VECSEL and OP-MIXSEL results are the state-of-the-art and world-record results. Prof. Keller’s group has pioneered SESAM modelocking, ultrafast VECSELs, and invented the MIXSEL device concept. In addition, they also introduced together with Dr. Telle from PTB the f-to-2f interferometer technique typically used to stabilize broadband frequency combs.

At the University of Neuchatel, the ERGO optical frequency comb built in collaboration between Prof. Keller’s and Thomann’s groups has shown the narrowest free-running CEO linewidth reported to date for a frequency comb in the 1.5-μm region. As a result, a tight phase lock of the CEO-beat can be much more easily realized than for a fiber comb and the achieved residual integrated phase noise of 0.72 rad rms for the locked CEO is one of the smallest values reported for a frequency comb system operating at 1.5-μm. The fractional frequency stability of the CEO-beat is 20-fold better than measured in a standard commercial fiber comb system and contributes only 10-15 to the optical carrier frequency instability at 1 s averaging time, which makes this comb very attractive as an optical-to-microwave frequency divider for all-optical ultra-low noise microwave generation.

At the EPFL, Prof. Eli Kapon’s group is a world leader in VCSELs emitting in the 1550 nm band thanks to the application of the wafer fusion technique for combining in the same monolithic device InP‐based active structure with GaAs‐based distributed Bragg reflectors.

Prof. Witzigmann’s group of the University of Kassel has developed leading tools and algorithms for the design and the analysis of semiconductor optoelectronic devices. Novolux has demonstrated >500 mW cw EP-VECSEL, but modelocking was limited to an average power of ≈50 mW. Based on Prof. Witzigmann’s simulations and first experimental results, a better understanding of the trade-off between cw and modelocking power optimization was gained. No academic group could reproduce the results that have been obtained by Novolux (which was supported by many 100 Mio $ venture capital funds).

ResultsThe project has demonstrated that diode-pumped solid-state lasers (such as an ERGO) can produce much more stable frequency combs. Furthermore timing jitter measurements of ultrafast OP-VECSELs have demonstrated that the noise is similar to diode-pumped solid-state lasers as expected in our proposal. The team therefore believes that the excellent frequency comb results presented here can also be achieved with the VECSEL and MIXSEL laser technology, which is very encouraging.

The ERGO optical frequency comb built in collaboration between Prof. Keller’s and Thomann’s groups and successively moved from ETH Zurich to LTF in Neuchâtel has shown very nice low-noise properties, resulting from the high Q-factor of the modelocked 1.5-µm diode-pumped solid-state laser. As a result, a tight phase lock of the CEO-beat can be much more easily realized than for a fiber comb. With a moderate feedback bandwidth of only 5.5 kHz, a residual integrated phase noise of 0.72 rad rms was achieved for the locked CEO, which is one of the smallest values reported for a frequency comb system operating in the 1.5-µm spectral region. The fractional frequency stability of the CEO-beat is 20-fold better than measured in a standard commercial fiber comb system. The stable CEO-beat observed with pulse durations up to 260 fs will have important impact on the development of more compact frequency combs operating with gigahertz repetition rates and is a promising step towards the realization of portable frequency combs based on MIXSELs.

A key element in a nonlinear microscope for biomedical applications is the use of an ultrafast laser. These are natural sources that are able to produce the required high intensities needed for exciting nonlinear processes. Historically, Ti:sapphire sources have been used in NLM due to its available large peak powers along with its large tunability range. However, its complexity, high price and maintenance requirements, have limited the widespread adoption of these powerful imaging techniques into daily routine biomedical applications. Within the FastDot team, it was experimentally showed, for the first time, that an ultrafast OP-VECSEL can be in fact used for nonlinear microscopy.

Ultrafast semiconductor lasers have the potential for a high level of integration which reduces packaging and manufacturing cost, important requirements for mass production. Modelocked edge-emitters achieve up to 250 mW of average power with 10-ps pulses, but dispersion, nonlinearities and end facet damage are severe challenges for achieving multi-watt power levels and for reducing the pulse duration into the femtosecond regime. Here we have reported on record-high average output power of a femtosecond VECSEL. The peak power of 200 W in combination with the high average power makes this source attractive for numerous applications such as frequency metrology and biomedical multi-photon imaging.

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PublicationsU. Keller, “Ultrafast solid-state laser oscillators: a success story for the last 20 years with no end in sight” – Invited Paper, Appl. Phys. B 100, pp. 15-28, 2010.

B. Rudin, V. J. Wittwer, D. J. H. C. Maas, M. Hoffmann, O. D. Sieber, Y. Barbarin, M. Golling, T. Südmeyer, U. Keller, “Novel ultrafast semiconductor laser with 6.4 W average output power” Optics Express 18, pp. 27582-27588, 2010.

R. Aviles-Espinosa, G. Filippidis, C. Hamilton, G. Malcolm, K. J. Weingarten, T. Südmeyer, Y. Barbarin, U. Keller, S. I. C. O Santos, D. Artigas and P. Loza-Alvarez, “Compact ultrafast semiconductor disk laser: targeting GFP based nonlinear applications in living organisms”, Biomedical Optics Express 2, No. 4, pp. 739-747, 2011.

M. Hoffmann, O. D. Sieber, V. J. Wittwer, I. L. Krestnikov, D. A. Livshits, T. Südmeyer, U. Keller, “Femtosecond high-power quantum dot vertical external cavity surface emitting laser” Optics Express 19, No. 9, pp. 8108-8116, 2011.

V. J. Wittwer, C. A. Zaugg, W. P. Pallmann, A. E. H. Oehler, B. Rudin, M. Hoffmann, M. Golling, Y. Barbarin, T. Südmeyer, U. Keller, “Timing jitter characterization of a free-running SESAM mode-locked VECSEL”, IEEE Phot. Journal 3, No. 4, pp. 658-664, 2011.

A. Chamorovskiy, J. Rautiainen, J. Lyytikäinen, S. Ranta, M. Tavast, A. Sirbu, E. Kapon, and O. Okhotnikov, “Raman fiber laser pumped by a semiconductor disk laser and mode locked by a semiconductor saturable absorber mirror,” Opt. Lett. 35, 3529-3531 (2010)

J. Lyytikäinen, J. Rautiainen, A. Sirbu, V. Iakovlev , A. Laakso, S. Ranta, M. Tavast, E. Kapon, and O. G. Okhotnikov “High-Power 1.48-μm Wafer-Fused Optically Pumped Semiconductor Disk Laser”, IEEE Photonics Technology Letters 23, no. 13, p. 917, 2011.

Chamorovskiy, A. Rantamäki, A. Sirbu, A. Mereuta, E. Kapon, and O. Okhotnikov, “1.38-µm mode-locked Raman fiber laser pumped by semiconductor disk laser,” Opt. Express 18, 23872-23877 (2010).

J. Rautiainen, J. Lyytikäinen, L. Toikkanen, J. Nikkinen and A. Sirbu, A.Mereuta, A. Caliman, E.Kapon and O. Okhotnikov, “1.3-μm Mode-Locked Disk Laser With Wafer Fused Gain and SESAM Structures”, IEEE Photonics Technology Letters 22, no. 11, p. 748-750, 2010.

G. Di Domenico, S. Schilt, P. Thomann, “A simple approach to the relation between laser frequency noise and laser lineshape”, Applied Optics 49(25), pp 4801-4807 (2010).

A. E. H. Oehler, M. C. Stumpf, S. Pekarek, T. Südmeyer, K. J. Weingarten, U. Keller, “Picosecond diode-pumped 1.5-µm Er,Yb:glass lasers operating at 10-100 GHz repetition rate”, Appl. Phys. B 99, Issue 1, pp. 53-62, 2010.

M. Hoffmann, O.D. Sieber, D. J. H. C. Maas, V. J. Wittwer, M. Golling, T. Südmeyer, and U. Keller, “Experimental verification of soliton-like pulse-shaping mechanisms in passively mode-locked VECSELs,” Opt. Express 18, Issue 10, pp. 10143-10153 (2010).

M. C. Stumpf, S. Pekarek, A. E. H. Oehler, T. Südmeyer, J. M. Dudley, and U. Keller, “Self-referencable frequency comb from a 170-fs, 1.5-μm solid-state laser oscillator,” Applied Physics B: Lasers and Optics 99, 401-408 (2009).

J. Lyytikäinen, J. Rautiainen, L. Toikkanen, A. Sirbu, A. Mereuta, A. Caliman, E. Kapon, and O. Okhotnikov, “1.3-µm optically-pumped semiconductor disk laser by wafer fusion,” Opt. Express 17, 9047-9052 (2009).

E. Saarinen, J. Puustinen, A. Sirbu, A. Mereuta, A. Caliman, E. Kapon, and O. Okhotnikov, “Power-scalable 1.57 µm mode-locked semiconductor disk laser using wafer fusion,” Opt. Lett. 34, 3139-3141 (2009).

A. R. Bellancourt, Y. Barbarin, D. J. H. C. Maas, M. Shafiei, M. Hoffmann, M. Golling, T. Südmeyer, U. Keller, “Low saturation fluence antiresonant quantum dot SESAMs for MIXSEL integration” Opt. Express 17, No. 12, pp. 9704–9711, (2009).

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NanowireSensorintegrateable silicon nanowire sensor platform

PrinciPal investigator

Prof. Christian schönenberger, uniBas

co-aPPlicants

Dr. Michel Calame, uniBas

Prof. Beat Ernst, uniBas

Prof. Jens Gobrecht, PsI

Prof. Andreas Hierlemann,

ETHZ

Prof. Adrian Ionescu, EPFL

Prof. uwe Pieles, FHNW

Prof. Janos vörös, ETHZ

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NanowireSensorINTEGRATEABLE sILICON NANOWIRE sENsOR PLATFORM

GoalsThere is nowadays a growing need for sensing devices offering rapid and portable analytical functionality in real-time as well as massively parallel capabilities with very high sensitivity at the molecular level. Such devices are essential to facilitate research and foster advances in fields such as drug discovery, proteomics, medical diagnostics, systems biology or environmental monitoring.

In this context, an ideal solution is an ion-sensitive field-effect transistor sensor platform based on silicon nanowires to be integrated in a CMOS architecture. Indeed, in addition to the expected high sensitivity and superior signal quality, such nanowire sensors could be mass manufactured at reasonable costs, and readily integrated into electronic diagnostic devices to facilitate bed-site diagnostics and personalized medicine. Moreover, their small size makes them ideal candidates for future implanted sensing devices. While promising biosensing experiments based on silicon nanowire field-effect transistors have been reported, real-life applications still require improved control, together with a detailed understanding of the basic sensing mechanisms. For instance, it is crucial to optimize the geometry of the wire, a still rather unexplored aspect up to now, as well as its surface functionalization or its selectivity to the targeted analytes.

This project seeks to develop a modular, scalable and integrateable sensor platform for the electronic detection of analytes in solution. The idea is to integrate silicon nanowire field-effect transistors as a sensor array and combine them with state-of-the-art microfabricated interface electronics as well as with microfluidic channels for liquid handling. Such sensors have the potential to be mass manufactured at reasonable costs, allowing their integration as the active sensor part in electronic point-of-care diagnostic devices to facilitate, for instance, bed-side diagnostics and personalized medicine. Another important field is systems biology, where many substances need to be quantitatively detected in parallel at very low concentrations: in these situations, the platform being developed fulfills the requirements ideally and will have a strong impact and provide new insights, e.g. into the metabolic processes of cells, organisms or organs.

Sensor platform for the electronic detection of analytes in solution – modular, scalable & integrateable

• Technique without biochemical labeling (no risk to alter target molecules, cheaper & faster)• No optical techniques which remain difficult to integrate at large-scale• Differential readout capability with in situ references (to prevent mis-readings)• Immediate or on-chip signal conditioning (to reduce noise)

Ion-sensitive field-effect transistor sensor platformbased on silicon nanowiresto be integrated in a CMOS architecture

Progress needed: understanding of thesensing mechanisms and improved control

SYSTEMS BIOLOGYPERSONALIZED MEDICINERobust / flexible / cheap platform to grant effectivediagnosis possibilities for healthcare specialists

Long-term vision: Embedded systems for constanthealth monitoring (diabetes, etc.)

Quantitative detection of numerous substancesin parallel at very low concentrations

For example: new insights into metabolic processesof cells, organisms and organs, etc.

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ContextThe development of reliable and flexible sensing systems at reasonable costs with adequate selectivity and sensitivity is a challenging task. Methods requiring biochemical labeling or amplification of the target analyte are costly and time-consuming. They additionally bear the risk to alter the target analyte molecules and affect the signal, which is an important issue for instance in gene expression assessment via DNA microarrays. Label-free techniques are, therefore, preferable.

Methods involving optical detection, such as surface plasmon resonance, have demonstrated their efficiency in affinity sensors. Optical techniques however remain difficult to integrate at large-scale, as required for the production of low-cost, portable sensing devices for applications in e.g. personalized medicine or smart wearable systems for life-quality improvement. Properly designed sensors also require differential readout capability with one or more in situ references to prevent mis-readings due to non-specific interactions or thermal drifts. Last but not least, highly sensitive detection systems will need immediate or in the best case on-chip signal conditioning to improve signal-to-noise ratio.

With due regard to all these boundary conditions, nanoscale electronic transducers based on ion sensitive field-effect transistors (FETs) that can be integrated in a silicon CMOS platform emerge as a promising choice. With this target in mind, there are several approaches that are currently tested world-wide. For example, the ability for electrical biosensing of nanoscaled FETs based on functionalized carbon nanotubes (CNTs) and solid-vapor phase grown semiconducting nanowires (NWs) are under consideration. Due to their small diameter, CNTs and NWs provide the potential for high density integration together with a large sensitivity due to the increased surface to volume ratio. The field of NWs has become one of the most active field in science in recent years. In contrast to the bottom-up route of grown NWs and CNTs, for which a systematic high-density integration remains an unsolved problem, we focus on NWs that are fabricated top-down using conventional microfabrication processes. This approach was pioneered by M. Reed et al. from Yale in 2007 and has been taken up by several other groups recently. The strength of the NanowireSensor project lies in the highly interdisciplinary consortium which brings in expertise form physics, chemistry, nanoelectronics and bioelectronics, system engineering and pharmacology. In our consortium all required aspects (fabrication, integration, surface chemistry, sensing assays) are represented, including the sensor company Sensirion, whose success is based on integrated Si-based sensors. As such, there is a good chance to elucidate the different mechanisms and come up with a successful concept that can be applied under standard physiological conditions.

ResultsAt the University of Basel, the Nanoelectronics group focuses on measurements of wires in liquid environment and the group of Molecular Pharmacy synthesizes the biomolecules and develops the pharmacological models. The EPFL partner designs and fabricates double-gated FinFET devices as functional non-linear amplifiers. At ETHZ, the Bio Engineering laboratory does system modeling and has designed and realized a first system platform for the integrated read out and the laboratory for Biosensors and Bioelectronics has developed a multiwire liquid sensing platform for the consortium. PSI is fabricating state-of-the-art nanowires which are used by all partners, and the FHNW partner does all surface chemistry, such as passivation and functionalization.

The NanowireSensor project has built wafers containing arrays of silicon nanowires with wire widths ranging between 70nm and 1μm. The nanowire field-effect transistors are of high quality displaying reproducible threshold voltages and low sub-threshold swing.

Silicon nanowires were passivated with an ALD-deposited top-oxide made of Al2O3 or HfO2. After passivation, the nanowires display low leakage currents and high gains in pH measurements with sensitivities close to the Nernst limit. A new flow-cell for the simultaneous measurements of many nanowires could be established and studies of the noise properties suggest that the signal-to-noise ratio can be surprisingly low.

A new type of ion-sensitive FET based on Fin-FETs were designed and first version were fabricated. The FinFET sensing element could be integrated in system simulation packages allowing to test alternative readout schemes.

A CMOS-based readout chip has been developed and fabricated. It enables the readout of multiple nanowires in parallel. Moreover the possibility to place or fabricate nanowires directly on the CMOS chip to achieve minimum length interconnects has been integrated. In the biological application on lectins, which are highly specific sugar-binding proteins, expressed for example in infections of the kidney, the team could electrically monitor for the first time the binding of such proteins on the silicon nanowires.

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PublicationsR. MacKenzie, C. Fraschina, T. Sannomiya, V. Auzelyte and J. Vörös, Optical Sensing with Simultaneous Electrochemical Control in Metal Nanowire Arrays, Sensors, Sensors 10(11): 9808-9830 (2010).

O. Knopfmacher, A. Tarasov, W. Fu, M. Calame, and C. Schönenberger, Sensitivity considerations in dual-gated Si-nanowire FET sensors. European Cells and Materials 20, Suppl. 3, 140 (2010) ISSN 1473-2262.

J. Kurz, U. Pieles, Ch. Schönenberger, Silicon Nanowires as Biochemical Sensors, European Cells and Materials 20 Suppl. 3, 151 (2010) ISSN 1473-2262.

A. Tarasov, W. Fu, O. Knopfmacher, J. Brunner, M. Calame, and C. Schönenberger, Signal-to-noise ratio in dual-gated silicon nanoribbon field-effect sensors, Appl. Phys. Lett. 98, 012114 (2011).

W. Fu, C. Nef, O. Knopfmacher, A. Tarasov, M. Weiss, M. Calame, C. Schönenberger. Graphene Transistors Are Insensitive to pH Changes inSolution. Nano Letters 11, 3597 (2011).

S. Rigante, L. Lattanzio and A. M. Ionescu, FinFET for High Sensitivity Ion and Biological Sensing Applications, Microelectronics Engineering 88:8, 1864 (2011).

R. MacKenzie, C. Fraschina, T. Sannomiya and J. Vörös, Controlled In Situ Nanoscale Enhancement of Gold Nanowire Arrays with Plasmonics, Nanotechnology 22(5), 055203 (2011).

U. Frey, U. Egert, F. Heer, S. Hafizovic, and A. Hierlemann, Microelectronic System for High-Resolution Mapping of Extracellular Electric Fields Applied to Brain Slices, Biosensors and Bioelectronics 24, no. 7, 2191-2198 (2009).

O. Knopfmacher, A. Tarasov, W. Fu, M. Wipf, B. Niesen, M. Calame, C. Schönenberger, Nernst Limit in Dual-Gated Si-Nanowire FET Sensors, Nano Letters 10, 2268 (2010).

U. Frey, J. Sedivy, F. Heer, R. Pedron, M. Ballini, J. Mueller, D. Bakkum, S. Hafizovic, F. D. Faraci, F. Greve, K.-U. Kirstein, and A. Hierlemann, Switch-matrix-based high-density microelectrode array in CMOS technology, IEEE Journal of Solid-State Circuits 45, no. 2, 467-482 (2010).

R. Gutierrez-Osuna and A. Hierlemann, Adaptive Microsensor Systems, Annu. Rev. Anal. Chem. 3, 255–76 (2010).

I. L. Jones, P. Livi, M. K. Lewandowska, M. Fiscella, B. Roscic and A. Hierlemann, The potential of microelectrode arrays and microelectronics for biomedical research and diagnostics, Analytical and Bioanalytical Chemistry, 2010, DOI 10.1007/s00216-010-3968-1.

O. Knopfmacher, D. Keller, M. Calame, C. Schönenberger, Dual Gated Silicon Nanowire Field Effect Transistors, Procedia Chemistry 1, 678-681 (2009).

M. Najmzadeh, L. De Michielis, D. Bouvet, P. Dobrosz, S. Olsen, A. M. Ionescu, Microelectronic Engineering 2009, to appear.

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NexrayNetwork of integrated miniaturized x-ray systems operating in complex environments

PrinciPal investigator

Dr. Alex Dommann, CsEM

co-aPPlicants

Dr. Pierangelo Gröning, EMPA

Prof. Hans von Känel, ETHZ

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Nexray NETWORK OF INTEGRATED MINIATuRIZED x-RAY sYsTEMs OPERATING IN COMPLEx ENvIRONMENTs

GoalsThis project targets the development of novel pocket X-ray sources and X-ray direct detectors that will be combined in a distributed network to solve important tasks, for example in the field of safety and security, by ensuring reliable and real-time monitoring of failure sensitive parts in large manufacturing plants or in public transportation.

The miniaturized X-ray sources are based on multi-wall carbon nanotube (CNT) cold electron emitters and advanced microsystems technology. The electron field emission properties of CNTs, with their high current densities, make them prime candidates for cold emitter cathodes. Using CNT cold electron emitters will make it possible to miniaturize the whole X-ray source to a tiny unprecedented volume. Additionally, as opposed to classical thermionic emission, field electron emission of the CNT is voltage-controlled which allows for high modulation frequencies up to GHz level. The X-ray direct detectors in turn are based on crystalline germanium absorption layers grown directly on a CMOS sensor chip yielding high resolution and high sensitivity X-ray detectors. Single photon detection will allow for a significant improvement of contrast for applications in security, health care and nondestructive testing.

A key application is in the area of tomographic imaging, making use of the fact that both the X-ray source and the X-ray detector are pixelated. Since the X-ray source is built as a matrix of micro X-ray sources that can also be addressed and controlled individually, the combination of pixelated X-ray sources and detectors brings up completely new imaging capabilities, in particular the possibility to do static tomographic imaging and therefore reduce costs or increase throughput.

Development of tera X-ray networks made of nano components

• X-ray sources - Based on carbon nanotube cold emitters CNT dimensions ensure a large electrical field enhancement factor low threshold voltage for electron extraction Miniaturization of the whole source to 1 mm3 only

• X-ray direct detectors - Based on cystalline Ge absorption layers grown directly on CMOS sensor chip Ge layer grown by low-energy-plasma-enhanced-vapour-deposition High resolution & high sensitivity, targeting single photon detection

Intensity modulated X-rays emitted are partly reflected back(Compton backscattering) Measurement of phase shift knowledge of reflection depth

Not achievable with conventional X-ray setups:

• Remittance of intensity modulated X-ray signal only possible with CNT based cold emitters• Data-preprocessing needed at the pixel level: only possible with CMOS-based detectors

Detection of buried landmines with knowledge of depth!

TOMOGRAPHIC IMAGINGX-RAY TIME-OF-FLIGHT MEASUREMENTSComputer tomography is a crucial tool in modern medicineNow: sources & detectors are rotated mechanically around the body

In this project:Both the X-ray detector and the X-ray source are pixelated this combination provides new imaging capabilites, e.g. static tomographic imaging

CT achieved by geometrical arrangement instead of mechanical movement

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ContextSeveral groups are involved in research concerning carbon nanotubes as field emitters for X-ray sources. Such novel X-ray sources have been realized by replacing the metal filament for thermal electron emission by CNT field emitters. However, no pixilated X-ray source array based on this technology has been realized so far. The miniaturization required for this task needs besides improved CNT films also advanced microsystems technology to cope with the electrical requirements of densely packed high voltage lines and long term stability of the required vacuum in small volumes.

Direct X-ray detectors based on semiconductor materials are already commercial products for low energy applications. Generally they offer an increased resolution combined with higher quantum efficiency when compared to scintillator based detectors or X-ray films. Several groups are involved in research concerning the use of materials with increased X-ray absorption compared to the classical semiconductor material silicon. Germanium has the advantage that the material is already established in CMOS processes. The required germanium-layer thickness is possible with the specialized LEPECVD technology used in this project. Especially the approach of epitaxial growth in constrained surface areas – the growth of isolated germanium pillars – has been shown in this project for the first time and represents a breakthrough in heteroepitaxy.

The combination of new miniaturized X-ray source arrays with high resolution and high efficient X-ray detectors make novel application possible like, e.g. static computed tomography (CT). Static CT, in general, allows for three-dimensional X-ray imaging of the internal structure of an object without moving the source or the detector. Due to the high integration on component level envisaged in this project an increased resolution compared to realizations with discrete single X-ray sources and detectors is targeted. Time-of-flight (TOF) measurements, another application, probe the distance to objects, in case of X-ray time-of-flight also to the internal object’s structure allowing three-dimensional imaging in reflection geometry. The technology requires a modulated source and a detector capable of determining the phase shift between the emitted and the detected signals. While optical TOF cameras show a resolution in the millimeter range, the technology has not been developed for X-rays so far. With the combination of modulated CNT X-ray sources and germanium X-ray detectors which will be developed in this project, such an application can be realized.

This project is expected to set a novel technological base and platform which will lead to high benefits notably in the fields of security and health, contributing thus to the wellbeing of humans.

ResultsFabrication technologies for carbon nanotube based electrodes have been established for carbon nanotube paste material and carbon nanotubes fabricated by controlled growth. A triode based layout for the miniaturized X-ray source has been refined and all microsystems technology based fabrication steps ensuring high voltage stability and vacuum tight encapsulation has been identified. A test device has been built for component and source system test. The first X-ray sources have been fabricated and characterized.

Fully relaxed germanium can be grown on microstructured silicon substrates as pillar structures eliminating the problems of layer cracking and wafer bowing of mismatched materials. It is thus possible to grow sufficiently thick germanium layers on CMOS wafers for X-ray detectors.

X-ray analysis shows excellent germanium crystal quality and electrical test a reasonable low dark current. In collaboration with a CMOS fab the process flow has been established. Test circuits for X-ray detection are currently in production; the CMOS design for a counting detector is expected to be completed by the end of 2011.

A key technical development consists in the definition of the fabrication steps of the miniaturized X-ray source. All technology steps have been identified encompassing CNTs electrode fabrication, triode set-up, X-ray exit window, electrical insulation and vacuum tight sealing. A test set-up allows operating X-ray sources in a vacuum chamber, i.e. here no vacuum tight sealing of the source is yet necessary.

Another key technical development consists in the definition of the fabrication steps of the monolithically integrated X-ray detector. Germanium pillars can be grown in large thicknesses onto microstructured Si-substrates eliminating cracks in the germanium layer and wafer bowing. The germanium-pillars are almost defect free; threading dislocations are located only near the Si-Ge interface. X-ray analysis shows excellent germanium crystal quality and electrical tests a reasonably low dark current. A design of a counting X-ray detector has been defined accounting for the characteristics of the Si-Ge heterojunction. The fabrication process has been established with the CMOS fab and test devices for first X-ray tests are in production.

An International Patent Application has been submitted, entitled “Dislocation and stress management by mask-less processes using substrate patterning and methods for device fabrication” (H. von Känel and L. Miglio).

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PublicationsC. Falub, H. von Kaenel et al., Scaling hetero-epitaxy from layers to three-dimensional crystals, accepted for publication in Science, 2012.

R. Kaufmann, G. Isella, A. Sanchez-Amores, S. Neukom, A. Neels, L. Neumann, A. Brenzikofer, A. Dommann, C. Urban and H. von Känel, J. Appl. Phys. 110, 023107 (2011).

A. Dommann, A. Neels, “X-Ray Strain Measurements In Strained Silicon Devices”, AIP Conf. Proc. 1378, 131 (2011).

A. Neels, A. Dommann, P. Niedermann, C.V. Falub, H. von Kaenel, Advanced Stress, Strain and Geometrical Analysis in semiconductor devices, AIP Conf. Proc. 1300, 114 (2010).

Add-on: COSMICMOS COMPLEx sTRuCTuREs MONOLITHICALLY INTEGRATED ON CMOs PLATFORM

PrinciPal investigator Dr. alex Dommann, CsEMco-aPPlicants Dr. Pierangelo Gröning, EMPa Prof. Hans von Känel, ETHZ

A technical breakthrough achieved within the NExRAy project, allows the epitaxial growth of Ge-layers of unparalleled thickness and quality on Si-substrates. While the novel process is suitable for the fabrication of x-ray absorbers, the team expects it to bring a solution also to long-standing problems associated with the monolithic integration of Ge and iii-V-semiconductor devices onto a silicon CMoS platform. To this end, the intention is to extend the underlying substrate patterning technique to the nano-scale range, and reduce layer thicknesses to values compatible with state of the art semiconductor processing. on the one hand, the project aims at a fundamental understanding of the processes responsible for defect-reduction in lattice mismatched semiconductor systems. on the other hand, the new technology will be tested by means of selected microelectronic and opto-electronic devices monolithically integrated on silicon.

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NutriChipa technological platform for nutrition analysis to promote healthy food

PrinciPal investigator

Prof. Martin Gijs, EPFL

co-aPPlicants

Dr. sandro Carrara, EPFL

Prof. Richard F. Hurrell, ETHZ

Prof. Jeremy Ramsden, uniBas

Dr. Guy vergères, ALP

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NutriChipA TECHNOLOGICAL PLATFORM FOR NuTRITION ANALYsIs TO PROMOTE HEALTHY FOOD

GoalsThe gastrointestinal tract plays a key role in the adsorption, distribution, metabolism, and excretion of nutrients, xenobiotics (drugs, toxins) as well as other molecules originating from commensal and pathogenic microorganisms. The intestinal epithelium is a tight gatekeeper controlling the uptake of nutrients and potentially harmful substances and the immune cell layer underlying the epithelial barrier is devoted to avoiding undesired reactivity to dietary proteins and enteric flora, while responding rapidly to pathogens threats. In light of the importance of gastrointestinal immuno-modulation, laboratory models have been developed, in particular, cell culture in vitro models involving a confluent layer of epithelial cells and a co-culture of immune cells separated by a permeable synthetic membrane. These models allow the activation of immune cells in response to the transfer and processing of molecules across the epithelial cell layer, and can potentially be used to screen food for specific physiological properties of nutrients. The classical cell culture design suffers, however, from a lack of efficiency when it comes to using such systems in a high throughput modus. It is therefore highly desirable to downscale such cell cultures and to make them more amenable to automation in order to promote efficient in vitro screening of the physiological properties of selected foods.

This is the major motivation of this project, focused on the development of an integrated lab-on-a-chip platform to investigate the effects of food ingestion by humans. The core of the system is an integrated chip, the NutriChip, which, as a demonstrator of an artificial and miniaturized gastrointestinal tract, will be able to probe the health potential of dairy food samples, using a minimal biomarker set identified through in vivo and in vitro studies. The project will develop innovative CMOS circuits at the nano-scale for high signal-to-noise ratio optical detection and propose a special microfluidic system closely integrating cell-based materials within the chip.

The NutriChip will be tested for screening and selection of dairy products with specific health-promoting properties, in particular immunomodulatory properties. The CMOS detection chip will be used to image down to single immune cells. For the biochemical validation of the NutriChip platform, the response of the immune cells upon the application of food will be examined by monitoring the Toll-like receptors 2 and 4, key molecules bridging metabolism and immuno-regulation in nutrition.

Goal : Create an integrated lab-on-a-chip platform to study the effect of human food ingestion

Core element: the NutriChip , probing health potential of dairy foods

Motivation…GIT: crucial for adsorption • distribution • metabolism • excretion of nutrients

Immuno-modulation role of intestinal epithelium: tight monitoring of the nutrients & potentially harmful substances

Cell models exist…Immune cells can be activated in response to transferof molecules (nutrients, etc.) through epithelial cell layer

Need to downscale cell cultures Adapt to automation for efficient in vitro screening of food properties

KEY DEVELOPMENTS

• Innovative nano-scale CMOS circuits for optical detection of GIT cells• Special microfluidic system integrating cell-based materials within chip• New algorithms for optimal real-time computation

Demonstrator of artificial & miniaturized gastrointestinal tract (GIT)

…but… culture design is inefficient for high throughput!RT

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ContextThe NutriChip project aims at screening a series of dairy products in vitro for their anti-inflammatory properties as well as to validate this in vitro model by assessing the ability of a selected dairy product to modulate inflammation in human intervention trials. The originality and innovation of the NutriChip project is a unique combination of state-of-the-art know-how and technologies in each of the scientific fields needed to conduct the project.

Scientists in the NutriChip project are members of the COST Action FA1005 (Improving health properties of food by sharing our knowledge on the digestive process - INFOGEST) that gathers European specialist in this field. The strength of the Swiss competences in the NutriChip project are the wide range of state-of-the-art biochemical analytics, the links to the clinical trials (see below) and to microfluidics and CMOS detection technologies. Also, European researchers in the field of food digestion only rarely introduce the in vitro transport and immune activation to the in vitro digestion step.

Several research groups, that are members of the NuGO organization, evaluate the response of human subjects to various diets using modern analytical methods of biology (nutrigenomics). The specificity of the human nutrition studies conducted in the context of the NutriChip project is the focus on whole food (instead of nutrients), the design of the intervention trials that incorporate a dose-response component to the studies, and more importantly, its unique link to the in vitro studies. Indeed, the foods investigated in vivo (high-fat meal, milk) are also investigated in vitro in the Transwell setting as well as in the NutriChip.

In vitro experiments for mimicking the GIT use cell culture inserts. These inserts require large amount of cells, samples and culture media and take long time to evaluate. A microfluidic approach has the potential to overcome these issues. Imuar et al (2009) developed a microchip that mimics the GIT intestine to investigate the intestinal absorption by culturing Caco-2 cells on a porous membrane in a PDMS microfluidic chip. In another recent study, the authors reported the integration of micro-intestine (Caco-2 cells), micro-liver (HepG2 cells) and a target component (human breast carcinoma MCF-7). Using this system, the activity of anticancer agents was studied. The NutriChip platform provides an efficient analytical tool which can be utilized to gain a holistic insight into the contribution of dairy products to human nutrition and health.

In terms of detection, TLR receptors have been already observed with fluorescent microscopy and also published in literature. However, a clear estimation of the total amount of TLRs on CaCo-2 cells still beyond the state-of-the-art of the present conventional fluorescent microscopy. The current system would be able to count the TLR receptors with images from conventional optical microscopes which to the team’s knowledge does not exist in literature.

ResultsAn immuno-competent artificial gastrointestinal tract (aGIT) has been established and its response to bacterial stimuli by an increased production of inflammatory markers by immune cells has been demonstrated in a Transwell device.

Additionally, an in vitro digestion process has been established and a standard operating procedure to digest and analyze dairy products to be tested in vitro is now made available.

In parallel, the engineering team has gained the necessary experience in cell culture using both macro-(Transwell device) and micro-(NutriChip) scale setups.

A first microfluidic device has been fabricated and characterized, and the outcome of this study has set the guidelines for design of the second version of the NutriChip. As for the imaging sensor, a commercially available CMOS image sensor has been integrated in a custom-designed system and compared to CCD sensors. High quality images were obtained. Finally, a plan for in vivo validation of the NutriChip has been established with the collaboration of Prof. K. Laederach (Inselspital, Bern).

The results of the project have been disseminated in general and specialized media:

- An article was published in the magazine “Technology by Bilan” on March 2nd, 2011 (G. Vergères et al. NutriChip - an electronic intestine for a healthy diet).

- G. Vergères, C. Egger, L. Corbino-Giunta and the NutriChip project were featured in the RSR1 radio program "Impatience" on 21 December 2011.

- C. Egger, K.A. Kopf-Bolanz, F. Schwander, B. Bogicevic, R. Portmann, M. Gijs, G. Vergères and the NutriChip project were featured in the SF1 TV Program "Einstein".

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PublicationsKatrin A. Kopf-Bolanz, Flurina Schwander, Martin Gijs, Guy Vergères, Reto Portmann, and Lotti Egger, Validation of an In Vitro Digestive System for Studying Macronutrient Decomposition in Humans, J. Nutr. January 1, 2012 jn.111.148635.

Qasem Ramadan, Hamideh Jafarpoorchekab, Katrin Bolanz, Flurina Schwander, Charlotte Egger, Reto Portmann, Paolo Silacci, Sandro Carrara, Jeremy Ramsden, Guy Vergeres and Martin A. M. Gijs. NUTRICHIP: an integrated microfluidic system for in vitro investigation of the immunemodulatory function of dairy products, in Proceedings of the 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Seattle, Washington, USA, October 2-6, 2011.

Gözen Köklü, Yusuf Leblebici, Sandro Carrara, A Switched Capacitor Fully Differential Correlated Double Sampling Circuit for CMOS Image Sensors, in Proceedings of the 5th International Symposium on Medical Information and Communication Technology (ISMICT 2011), Montreux, March 27-30, 2011, p. 113-116.

Add-on: Ca-NutriChipNuTRICHIP FOR MONITORING THE BIO-AvAILABILITY OF CALCIuM

PrinciPal investigator Prof. Martin Gijs, EPFLco-aPPlicants Dr. sandro Carrara, EPfL Dr. Guy Vergères, ALP

The Ca-NutriChip project will extend the Nutrichip micro-artificial gut platform by adding a nutrikinetic capability, focusing on the bio-availability of calcium in dairy products as a model system. The Ca-NutriChip platform will be able to quantitatively monitor the adsorption and transport of Ca through the epithelial cell layer as well as it’s uptake by target cells, and this in a time-resolved manner. The importance of pharmacokinetics has long been recognized in medicine and pharmacology and adsorption, distribution, metabolism, and excretion (ADME) studies are essential components for the development of efficient and safe drugs. in nutrition research, the concept of nutrikinetics still is in its infancy, but will undoubtedly advances its future development. Ca plays a major role in health and disruption of Ca homeostasis is associated with many diseases, such as osteoporosis, obesity, diabetes, cancer, hypertension, cardiovascular diseases, and kidney stones. As such the Ca-NutriChip adds an innovative and important complement to the original project, valorizing even more the multiple nano- and tera-aspects of the original Nutrichip platform. The knowledge gained from this research project can ultimately be used to investigate the bioavailability of other nutrients and therefore can serve as a paradigm for nutrient adsorption.

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OpenSense open sensor networks for air quality monitoring

PrinciPal investigator

Prof. Karl Aberer, EPFL

co-aPPlicants

Prof. Boi Faltings, EPFL

Prof. Alcherio Martinoli, EPFL

Prof. Lothar Thiele, ETHZ

Prof. Martin vetterli, EPFL

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OpenSenseOPEN sENsOR NETWORKs FOR AIR QuALITY MONITORING

GoalsWireless sensor networks and publishing of sensor data on the Internet bear the potential to substantially increase public awareness and involvement in environmental sustainability. These technologies enable capturing sensor data by involving public authorities and the general public and making real-time information on environmental conditions available to a wide public. Air pollution monitoring in urban areas is a prime example of such an application as common air pollutants have direct effects on human health, thus becoming an extremely important environmental issue in large areas of the world due to increasing urbanization. However, bringing the vision of public involvement in environmental monitoring to a reality poses substantial technical challenges, to scale up from isolated well-controlled systems to an open and scalable infrastructure where many nano-scale sensors generate terabytes of data.

Challenges that are not well addressed today are dealing with the heterogeneity and widely varying characteristics of the sensor equipment, measurements and data analysis, supporting and exploiting mobility of sensors and involving the community in a trusted, fair and transparent manner into the monitoring activity. Air pollution monitoring is particularly suited to study these challenges as they are particularly pronounced in this scenario. A wide variety of sensors (meteorological data, air pollutants and fine particles) are used, normally not integrated with one another, with measurements sharing complex atmospheric chemistry and transport processes. These monitors could be stationary or mobile (public and private vehicles, personal devices, airborne vehicles) providing real-time information and warnings on air pollution that is of great public health importance.

OpenSense addresses key research challenges in the domain of information and communication systems related to community-based sensing using wireless sensor network technology in the context of air pollution monitoring. Solutions to these problems affect typically all layers of information and communication system architecture, with interdependencies and synergies among the different layers. For that reason the research team consists of experts in signal processing, networking, robotics, data management and qualitative reasoning. The project will result in open technology that allows integrating diverse sensors, including mobile sensors, into a single environmental model. The information processing techniques we develop will provide important insights to enable other Nano-Tera.ch application domains dealing with monitoring complex events.

Urban air pollution:• Important health problem• Highly location-dependent (traffic chokepoints, industries, etc.)• Few monitoring stations measure pollutants

Goal: Address key challenges in communication and information systems for urban air quality monitoring

Sensing • Mobile sensor nodes on public buses infrastructure: and private mobile devices • Wireless sensing and communication infrastructure

Need to compress, clean & interpret the huge amount of data generated

Identify and exploit spatial & temporal correlations in sensor data to perform optimizations

MOBILE SENSORS

• Intermittent communication• Sensor position changes constantly• Need to minimize measurements to reduce power consumption

Networks grow without central planning, require self-organizing & autonomously acting components

COMMUNITY SENSING

Air pollution monitoring: high public interest

Make gathered data available in understandable & individualized to a large community

With producers of data: issues of reliability and trustworthiness of the information

Main challenges and research areas:

USE OF CORRELATIONS

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ContextOpenSense in comparison to the international competition in the general area of participatory sensing can be set apart by the following features:

OpenSense is quite unique in terms of producing dense measurements in the domain of air pollution monitoring using mobile measurement stations and aiming at long-term measurements. Moreoever, OpenSense is dealing with a difficult measurement problem (as compared to other participatory sensing projects that use readily available data, e.g., from smartphones such as sound, accelerometer and GPS data). Finally, OpenSense is unique in adopting and end-to-end systems perspective assembling IT expertise concerning all system layers, whereas comparable projects usually focus on specific subproblems.

For comparison below are some of the more related projects and the main differences.

- Older (London Air Quality Network) and more recent sensor networks projects (e.g. CitySense) use static stations only and thus are biased by selection sites and require larger number of sensor to be deployed.

- In the environmental engineering community, the Marshall Research Group at the University of Minnesota has made a considerable research effort in order to increase the spatial and temporal resolutions of the data obtained from classical air monitoring systems (sparse networks of static monitoring stations, remote sensing). While the statistical extrapolation method they use, called land-use regression (LUR), delivers quite impressive improvements in the spatial domain, it is still quite limited in terms of temporal resolution and the typical outputs are seasonal or monthly averages.

- Ongoing projects on mobile air quality monitoring with similar goals such as MAQUMON and Haze Watch, use passive open sampling systems and don’t target adaptive control of the activities of the sensor network.

- Projects on participatory sensing with environmental focus such as CitySense, Senseable, UrbanSensing or MetroSense focus on data captured by personal devices in particular smartphones.

- Safecast and Tokyo Hackerspace, a collaboration between Keio University and MIT Media Lab is currently performing radiation monitoring in Japan. Their project does not provide real-time access to the data.

ResultsThe project made significant progress in developing the mobile sensing platform, with first test deployments realized both on the bus network in Lausanne and the tram network in Zürich, with the support of Transport Lausanne (T-L) and VBZ in Zürich. The sensing systems have been developed in close collaboration with researchers from SwissTPH, Fachhochschule Nordwestschweiz (FHNW) and EMPA/BAFU providing expertise on air quality sensors. Significant progress has been made in understanding sensor behavior and in particular on calibration methods exploiting sensor mobility. First datasets including O3, NO2, CO and fine particles have been obtained and are now being analyzed using various statistical and machine learning techniques. The data is being made accessible through a Web-based platform in real-time.

In terms of sensor data analysis and sensor control the project resulted in a number of new techniques. We developed route selection and scheduling algorithms for optimizing measurement scheduling on a transport network. A mobility simulator enables microscopic traffic simulation for accurate public transportation modeling. A qualitative, region-based model will allow us to reconstruct from sparse, mobile measurements a complete picture of air pollution in a given area. We obtained theoretical results on optimal trajectories and reconstruction schemes for sampling of spatial pollution fields using mobile sensors. Model-based sensor data compression techniques have been developed to optimize transmission and storage of large amounts of sensor data and model-based data cleaning techniques enable automated identification of erroneous data and outliers. We analyzed the tradeoffs among protecting data privacy at sensor nodes and the data accuracy obtained from the transmitted sensor data. We developed lightweight data privacy protection schemes that can be run on mobile devices. With algorithms for automated semantic activity recognition from GPS traces we will be able to target information to users depending on their current activity. In order to orchestrate the interplay among these different models and control schemes at the various system layers of the sensing system, we are developing integration strategies based on a common utility-based framework.

The team managed to establish contacts of strategic importance to the health domain, sensor producers and service providers, which will be invaluable to make the project practically, societally and economically valid. The collaboration with Nokia research center is a key success for OpenSense demonstrating that the project has not only public interest but also commercial potential. Already in the initial phase the project receives high attention within Nokia.

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PublicationsO. Saukh, D. Hasenfratz, A. Noori, T. Ulrich, and L. Thiele: Route Selection for Mobile Sensors with Checkpointing Constraints, Proc. of the 8th International Workshop on Sensor Networks and Systems for Pervasive Computing (PerSeNS 2012), Lugano, Switzerland, March 2012.

D. Hasenfratz, O. Saukh, and L. Thiele, On-the-fly Calibration of Low-cost Gas Sensors, Proc. of 9th European Conference on Wireless Sensor Networks (EWSN 2012), Trento, Italy, Feb. 2012.

Karl Aberer, Saket Sathe, Dipanjan Chakraborty, Alcherio Martinoli, Guillermo Barrenetxea, Boi Faltings, Lothar Thiele, OpenSense: Open Community Driven Sensing of Environment, ACM SIGSPATIAL International Workshop on GeoStreaming (IWGS) 2010 (along with ACM GIS 2010).

A. Arion, H. Jeung, K. Aberer, Efficiently Maintaining Distributed Model-Based Views on Real-Time Data Streams, Proceedings of the Global Communications Conference, GLOBECOM 2011, Houston, Texas, USA.

Z. Chen, G. Barrenetxea, and M. Vetterli. Distributed Successive Approximation Coding using Broadcast Advantage: the Two-Encoder Case, in 48th Annual Allerton Conference on Communication, Control and Computing, 2010.

H. Jeung, S. Sarni, I. Paparrizos, S. Sathe, K. Aberer, N. Dawes, T.G. Papaioannou and M. Lehning, Effective Metadata Management in Federated Sensor Networks, Proceedings of The Third IEEE International Conference on Sensor Networks, Ubiquitous, and Trustworthy Computing, 2010.

J. J. Li, B. V. Faltings, Towards a Qualitative, Region-Based Model for Air Pollution Dispersion, IJCAI Workshop on Space, Time and Ambient Intelligence (STAMI), 2011.

I. Paparrizos, H. Jeung and K. Aberer, Advanced Search, Visualization and Tagging of Sensor Metadata, Proceedings of the IEEE International Conference on Data Engineering (ICDE), 2011.

T. G. Papaioannou, M. Riahi, and K. Aberer. Towards Online Multi-Model Approximation of Time Series, in MDM 2011 - 12th International Conference on Mobile Data Management, 2011.

I. Rolewicz, M. Catasta, H. Jeung, Z. Miklos, K. Aberer, Building a Front End for a Sensor Data Cloud, in Proceedings of International Workshop on Cloud for High Performance Computing (C4HPC), 2011.

S. Sathe, H. Jeung and K. Aberer, Creating Probabilistic Databases from Imprecise Time-Series Data, Proceedings of the IEEE International Conference on Data Engineering (ICDE), 2011.

J. Unnikrishnan and M. Vetterli, Sampling trajectories for mobile sensing, to appear in Proc. of Forty-Ninth Allerton Conference on Communication, Control, and Computing, Monticello, IL, Sept. 2011.

Z. Yan, D. Chakraborty, C. Parent, S. Spaccapietra, K. Aberer, SeMiTri: A Framework for Semantic Annotation of Heterogeneous Trajectories, 14th International Conference on Extending Database Technology (EDBT), 2011.

Add-on: OpenSense+OPEN sENsOR NETWORKs FOR AIR QuALITY MONITORING

PrinciPal investigator Prof. Karl Aberer, EPFLco-aPPlicants Prof. Boi Faltings, EPFL Prof. Lothar Thiele, ETHZ Prof. Martin Vetterli, EPFL

The objective of this add-on project is to explore, in collaboration with Nokia Research Center, Lausanne, some of the fundamental challenges that lie in provisioning effective and efficient personal health services through online and mobile technologies. openSense explores community-driven monitoring of environmental factors impacting human life, in particular air pollution, exploiting wireless and mobile sensors attached to private of public vehicles. The goal is to produce fine-grained models of dynamic environmental parameters, exploiting mobile sensors, a paradigm shift from the macro-updates we receive today. This RTD add-on project expands the scope of openSense to explore research questions for delivering such dynamic data and services to the community – the human consumers, through mobile consumer-facing service platforms. This largely impacts end user services in the domain of preventive health care. The project will be carried out in close collaboration with the Nokia Wellness diary, a recent strategic platform for delivering wellness related on-line services.

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Principal investigator Dr. Harry Heinzelmann, CSEMCo-applicants Prof. Jürgen Brugger, EPFLProf. Nico de Rooij, EPFLProf. Hans Peter Herzig, EPFLDr. Agnese Mariotti, CePoProf. Ernst Meyer, uni BaselProf. Pedro romero, uNiLProf. Horst Vogel, EPFL

PATLiSciProbe array technology for life science applications

PrinciPal investigator

Dr. Harry Heinzelmann, CsEM

co-aPPlicants

Prof. Jürgen Brugger, EPFL

Prof. Nico de Rooij, EPFL

Prof. Hans Peter Herzig, EPFL

Dr. Agnese Mariotti, CePO

Prof. Ernst Meyer, uniBas

Prof. Pedro Romero, uNIL

Prof. Horst vogel, EPFL

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PATLiSciPROBE ARRAY TECHNOLOGY FOR LIFE sCIENCE APPLICATIONs

GoalsThe development of techniques based on micromechanical force sensors (micro-cantilevers) is of increasing importance for applications in biological sciences. Scanning force microscopy and related techniques allow for high resolution imaging e.g. of membrane proteins, offering unprecedented insights into their structure and their functioning. Furthermore, related non-imaging methods such as force spectroscopy allow studying the mechanics and the adhesion forces between materials ranging from proteins to entire cells. An impressive body of literature on mechanical properties of molecules and their interaction forces has been generated in the recent past. However, little has been done so far on a cell level, due to the complexity and the number of the experiments to be conducted.

Interestingly, it has been shown recently that the stiffness of cancer cells affects the way they spread in the body. Equally important are the adhesion forces of cancer cells to other cells. The measurement of nanomechanical properties of cells as well as cell-cell interactions as a function of milieu parameters is thus of particular interest in cancer research.

The projects addresses oncology at a molecular level, by analyzing the presence of biomolecular markers involved in cancer diseases, and at a cellular level, by studying mechanical and adhesion properties of cancerous cells. First of all, it will develop non-invasive and early diagnostics tools for the detection of cancerous biological markers that can be used by medical doctors. The goal is to detect circulating tumor cells (CTC) in peripheral blood of cancer patients through the analysis of tumor specific markers in enriched samples or by direct trapping of the CTCs; as well as detect volatile organic compounds present in the exhaled breath of patients suffering from head and neck cancer. Moreover, the project seeks to acquire a better understanding of the biological processes involved in cancer diseases, such as proliferation of cancerous cell or activation of melanoma cells. On the one hand, the relation between elastic properties (cell elasticity) of cancerous cells and their degree of malignancy, invasive and metastatic properties will be analyzed and characterized. On the other hand, the adhesion properties of cancerous cells will be determined and characterized to understand how they are influenced by the tumor microenvironment, i.e. by the interaction with other cells and by the nature of the extracellular matrix.

The project PATLiSci is composed of two main parts, namely the nanomechanical sensing of biomolecules (“nanomechanical nose”) and the development of cantilever arrays for highly parallel force spectroscopy. Both project parts share common technological challenges, such as microfabrication issues and surface functionalization, as well as the main field of application, which is cancer research.

Micro-mechanical force sensors (micro-cantilevers) exhibit properties that make them usable as highly sensitive probes to detect molecular species adsorbed to them

Develop probe array techniques for life science applications, particularly in the context of cancer research

Indeed, cancer spread in the body depends on... • stiffness of cancer cells • adhesion forces of cancer cells to other cells

Nano-mechanical properties of cells & cell-cell interactions are therefore crucial in cancer research

AFM based force spectroscopy on & between cells

Cantilever based nanomechanical sensing of specifically adsorbed species with high detection limit

Adsorbants affect the cantilever’s mechanical properties (its mass, hence its resonance frequency) and can be readily detected «Mechanical nose»: numerous cantilevers in parallel, each responsible for the detection of a given target substance

EXPECTED BREAKTHROUGHSAdvancement of personalizedmedical diagnostics

Direct impact onpharmacological research& cell-based drug screening

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ContextCantilever array sensors in liquid are used here to detect RNA and DNA hybridization in a mechano-chemical way, allowing to study molecular interactions directly at the cantilever sensor surface at high sensitivity. In contrast to other competing technologies like Surface Plasmon Resonance, our signal is directly associated to changes in the molecular layer, i.e. surface stress and conformational changes are measured directly, whereas the SPR signal relies on an indirect detection of binding based on optics, i.e. refractive index changes. Moreover, cantilever array sensing is label- and amplification free in contrast to well-plate based DNA/RNA array formats.

The membrane-based sensors for detection of volatile compounds associated with cancer markers or their by-products in breath samples of cancer patients represent a substantial improvement in sensitivity compared to previously available piezoresistive cantilevers and other electronic nose concepts. The technology allows to construct a compact an easy-to-use portable measurement system involving micropumps, sensor electronics and data acquisition in a single USB-powered box controlled by a laptop computer.

The use of AFM-based technique to measure mechanical properties of cancerous cells or the measure cell adhesion properties started in the late nineties. Several groups are active in this field, leading to numerous publications. All these experiments were realized with single AFM probes. Both mechanical or adhesion properties of cell needs to be analyzed on a large number of samples in order to determine the minute differences by improved statistics, which requires extreme long investigation time. Performing the measurements in parallel by the utilization of 2-dimensional probe arrays would drastically increase the measurement throughput. Whereas different groups are working on the implementation of 2-dimensional probe arrays, almost nobody is investigating on the application of AFM probe-arrays for cellular mechanical and adhesion properties, although an increased throughput is demanded. The project addresses exactly this domain: it will develop a parallel AFM platform using 2D probe arrays for the investigation of adhesion and mechanical properties of living cells, and investigate both cellular properties regarding the malignant character of melanomas in different development phases.

ResultsBoth parts of the project (nanomechanical sensing based on cantilever arrays, and parallel force spectroscopy based on probe arrays) share a considerable amount of base technology, and their field of application.

In the nanomechanical sensing part, available piezoresistive cantilevers have been characterized with different analyte vapors, and their optimum geometries have been determined. A new design, sensing membranes, have shown superior performance in simulations, which were confirmed by first tests on an out-of-project batch of such structures. For detecting cells rather than gaseous analytes, both the detection of mRNA/DNA and cell surface markers as well as the monitoring of the cell capture events in the force signal were accomplished.

In the parallel force spectroscopy part, first generation probe arrays have been fabricated with a wide range of force constants and tip radii. For actuated probes, the thermo mechanical response has been simulated and first test structures have been fabricated. The overall setup has been further developed, and optical access has been optimized by the incorporation of a phase contrast microscope (in-house design). For a compact optical setup, several approaches featuring lens arrays are being evaluated. Different strategies to generate cell arrays have been tested. Cell mechanics and cell adhesion as a function of malignancy have been measured by AFM and optical tweezers.

The Science Prize of the State of Basel 2011 goes to Prof. Dr. Christoph Gerber of the Swiss Nanoscience Institute and the Department of Physics at the University of Basel for his extraordinary and world-wide recognized pioneering work in the field of nanotechnology, in particular for the development of highly sensitive sensors in biology, chemistry and medicine.

Christoph Gerber will receive the Life time Achievement Award February 2012 for his achievements in AFM technologies, in particular for application in life sciences, established 2004 by Nature Publishing Group, Nature Biotechnology, Nature Medicine, Nature Nanotechnology. Previously, 3 Nobel laureates are among the recipients of this prestigious award.

PublicationsM. Favre, J. Polesel-Maris, T. Overstolz, P. Niedermann, S. Dasen, G. Gruener, R. Ischer, P. Vettiger, M. Liley, H. Heinzelmann, and A. Meister, Parallel AFM imaging and force spectroscopy using two-dimensional probe arrays for applications in cell biology, J. Mol. Recognit. 24, 446–452 (2011).

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Add-on: MINACELMICRO- AND NANOFLuIDICs FOR CELL HANDLING

PrinciPal investigator Dr. Harry Heinzelmann, CSEMco-aPPlicants Prof. Ernst Meyer, uniBas Prof. Philippe renaud, EPfL

Two Nano-Tera RTD projects, PATLiSci and LiveSense, are involving living eukaryotic cells. PATLiSci aims to develop research and portable diagnostic tools for oncology. Microcantilever probe arrays will be used as biochemical sensing and force sensing for detecting biological markers expressed by cancerous cells and for measuring adhesion and mechanical properties of cancerous cells. The goal of LiveSense is to develop a microbioreactor device and microfluidic for on-line water quality analysis using living cell monitoring.

This Nano-Tera extension project MiNACEL seeks to bridge these two ongoing RTD projects, to share complementary competences, in the field of microfluidic for cell handling in particular. A portable microbioreactor, like for LiveSense, will enable to grow cancerous cells and to collect volatile organic compounds used as cancer markers, which will then be detected by biochemical sensing. This approach offers the advantage to obtain “in-vitro” results that can be compared with measurements from patients. Two other microfluidic devices, to sort circulating tumor cell from blood, and to handle and manipulate individual adherent cells, will also be developed.

Additionally, a post analysis of cells will be made by performing microinjection or sampling of the cytoplasm. To this aim, microcantilevers with embedded nanofluidic channels will be used. Thanks to the force sensor, the cell should not be damaged during the handling.

LiveSense can here provide expertise in microfluidic networks for cell sorting and the development of the microbioreactor. on the other hand LiveSense can profit from this work by having access to new sensors for analyzing cell culture responses to different environments thus increasing the number of analytical tools at their disposal.

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Principal investigator Prof. Qiuting Huang, ETHZCo-applicants Dr. Catherine Dehollain, EPFLProf. Christian Enz, CSEM

PlaCiTUSPlatform circuit technology underlying heterogeneous nano and tera systems

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PrinciPal investigator

Prof. Qiuting Huang, ETHZ

co-aPPlicants

Dr. Catherine Dehollain, EPFL

Prof. Christian Enz, CsEM

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PlaCiTUSPLATFORM CIRCuIT TECHNOLOGY uNDERLYING HETEROGENEOus NANO AND TERA sYsTEMs

GoalsThe revolution in information and communication technology that is taking information flow into the era of tera-bits and the biomedical advances down to molecular scale would not have taken place without the accompanying downscaling of CMOS technology to the nano scale device size and tera system complexity. This aggressive downscaling has allowed the number of transistors per chip to be increased, thus extending their functionality and pushing up speed performance. However, this is obtained at the cost of severe degradation in certain quality metrics, such as increase of parameter variability, strong degradation of device matching, and increase in leakage currents including gate leakage, stronger short-channel effects (weak-inversion slope reduction, drain-induced barrier lowering, etc), ever lower supply voltage, novel degradation mechanisms and increasing reliability constraints. The profound changes in the device structure that are required to mitigate or eventually circumvent all these degradations will obviously have a significant impact on the way circuits, and particularly analog and RF circuits, have to be designed.

It is therefore crucial to fully understand the operation and limitations of these devices in order to design robust digital, analog and RF circuits. In the next decade, the challenges to the semiconductor industry and the applications it supports will lie not so much in realizing smaller and faster transistors as in how to make the best out of the billions of transistors per chip we already have. Understanding how to handle complexity in mixed signal embedded systems is therefore crucial for the next generation of applications that deal with health, microsystems and communications. How to partition system functionality into digital, analog and RF or sensor realizations on a system on chip optimally is one of the key topics that will impact the era of nano CMOS technologies.

This project investigates the challenges in mixed signal platforms, such as those embedded in biomedical electronics, micro-systems, sensor networks and wireless communications, from both device and systems perspective. Demonstrators will be developed that cover generic sensor interface/data acquisition, passive telemetry, wireless body area network, wireless sensor networking and wireless wide area networks. The achievements will benefit other Nano-Tera projects focusing on the sensor/actuator side of microsystems, as well as wireless communications SoCs that will challenge the state-of-the-art in integration level, versatility and sophistication of nano CMOS systems.

In the last decades: downscaling of CMOS technologies has led to higher transistor density & speed performance... but... at the cost of severe degradation in quality metrics!

• Generic sensor interface/data acquisition • Passive telemetry • Wireless body area networks • Wireless sensor networking • Wireless wide area networks

GENERAL APPLICATIONFrom sensors in & on the body, forming the wireless body area network, to the wireless wide area network

DEMONSTRATORS IN THE FOLLOWING AREAS

• Increase of process parameter variations • Degradation of component matching • Increase of leakage currents • Stronger short channel effects • Ever lower supply voltage

Profound structural changes are required !

Goal here: Build a platform for the design of complex mixed-signal system-on-chip in nano-scale CMOS for health, security & environment applications

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ContextRegarding data acquisition and remote powered biomedical front ends, the principal investigator had published remote powered, 250 µW data acquisition and telemetry IC more than a decade ago, but focused on other research topics in the intervening years until the start of the PlaCiTUS project. Both the PI and Co-PI (CSEM) have also been acknowledged experts in chopper amplifiers. In recent years international efforts in the field intensified. Remote powered biomedical sensors for blood pressure have been published by Cong et al., and data acquisition for bio signals by Yeager et al in 2010. Co-PI EPFL is now focusing on an interesting medical application to study animal and human obesity in close collaboration with three other laboratories at EPFL. This study is based on the measurement of internal body temperature in mice, performed in vivo. The EPFL Co-PI has designed the sensor interface, which is compatible with both internal body temperature measurement and other medical applications (e.g. EEG, ECG). Remote powering is crucial here, and two different frequencies will be used in order to achieve wireless remote powering of the implanted sensor and data communication separately. The PI ETHZ is developing a multi channel interface to electrodes, where the focus is on cancellation of electrode offset, low noise amplifier, high performance ADC and digital system interface.

On short-range wireless link radio, the combination of MEMS devices with RF circuits has demonstrated great potential for achieving low-power consumption and extreme miniaturization levels required in many applications such as WBAN. Extensive work has been carried out in recent years by CoI CSEM and the groups of Prof. B. Otis (University of Washington) and Prof. J. Rabaey (UC Berkeley). While the latter have mostly focused on wake-up radios, CSEM is developing complete radios for WBAN applications in the 2.4 GHz band using Bluetooth Low-energy (BT-LE) and ZigBee protocols. New radio architectures are being investigated that take advantage of the MEMS features (such as their high quality factor) and circumvent their drawbacks (such as reduced frequency tuning range). The combination of MEMS packaged in a vacuum package with the radio IC enables extremely small radios as required by WBAN.

These radios use constant-envelope modulations, which can take advantage of phase-ADCs. The basic principle of a phase ADC is to add two sine waves (the in-phase and quadrature phase components of the received signal) by using a linear network to generate phase shifted sinusoids whose phase information can be recovered by using zero-crossing detectors. The motivation of using a phase-ADC in the receive part of a radio is mainly to avoid the classical amplitude ADC, which remains one of the most power hungry and area consuming blocks in a digital radio, hoping that a lower power consumption can be achieved with a phase-ADC thanks to its much lower complexity.

Finally, concerning the wide area wireless link radio, the PI ETH has been a pioneer in cellular radio research since more than a decade, especially for introducing RF CMOS technology that has been widely adopted by industry today. While legacy standards such as GSM are well understood, leading research groups such as ETH continue to introduce innovation to the wireless transceiver field in 3G and 4G standards. ETH recently pioneered SAW-less HSPA transceiver technology. Because of its importance there are many research groups active in the field, both in industry and research institutions. IMEC and Nokia are among the leading players. With the forthcoming 4G LTE standard, research into multi frequency (more than 40!), multi band and broadband RF techniques has intensified. Some of the research undertaken in PlaCiTUS represents the forefront of this research area.

ResultsSystem level studies identified typical requirements for an integrated circuit platform to support applications related to the Internet of Things, including but not limited to sensor interface, wireless sensor network, and their application to healthcare. Challenges in complex system design involving miniaturized (nano) transistors for high performance and broadband (tera) applications have also been considered. Phased approach to studying and meeting those challenges has been planned.

Demonstrators have been planned, and circuit subsystems critical to a versatile platform of technologies have been identified. Designs of many such subsystems have been carried out. They include low noise amplifiers, A/D converters, a data acquisition subsystem, short-range radio receiver and transmitter, and software defined data converters and filters for wide area wireless communications. Some of the designs have returned recently. The initial batch of experimental results has been very encouraging.

Among other significant facts related to the PlaCiTUS project, the PhD student Raghavasimhan Thirunarayanan at CSEM obtained the best student paper award at the IEEE NewCAS Conference for his paper entitled “Complementary BAW Oscillator for Ultra-Low Power Consumption and Low Phase Noise”.

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PublicationsX. Liu, C. Dehollain, “A non-linear model for micropower rectifiers in UHF-bands RFIDs,” IEEE ICECS Conference, Dec. 2010.

D. Ruffieux, M. Contaldo, J. Chabloz, and C. Enz, “Ultra Low Power and Miniaturized MEMS-based Radio for BAN and WSN Applications,” Proc. of the European Solid-State Circ. Conf. (ESSCIRC), pp. 71-80, Sept. 2010.

B. Banerjee, C. C. Enz, and E. L. Roux, “A 290µA, 3.2MHz 4-bit Phase ADC for Constant Envelope, Ultra-low Power Radio,” Proc. of the NORCHIP conf., pp. 1-4, Nov. 2010.

M. Contaldo, B. Banerjee, D. Ruffieux, J. Chabloz, E. L. Roux, and C. C. Enz, “A 2.4-GHz BAW-Based Transceiver for Wireless Body Area Networks,” IEEE Trans. on Biomedical Circuits and Systems 4, no. 6, pp. 391-399, Dec. 2010.

R. Thirunarayanan, A. Heragu, D. Ruffieux, and C. Enz, “Complementary BAW Oscillator for Ultra-Low Power Consumption and Low Phase Noise,” Proc. of the 10th Int. NewCAS Conf. (NewCAS 2011), pp. 97-100, June 2011 (Best Student Paper Award).

T. Christen, “Multi-Mode Delta-Sigma A/D-Converters for Multi-Standard Wireless Receivers”, Hartung Gorre, 2010.

J. Treichler and Q. Huang, “A 11.1- Bit ENOB 50MS/s Pipelined A/D Converter in 130nm CMOS Without S/H Front End", Proceedings of the 2010 European Solid-State Circuits Conference (ESSCIRC 2010), pp. 374-377, Sevilla, Spain, Sept. 2010.

Q.Huang, C. Dehollain, Ch. Enz, T. Burger, “A circuit technology platform for medical data acquisition and communication: Outline of a collaboration project within the Swiss Nano-Tera.ch Initiative”, Proceeding of the IEEE DATE 2011 conference, Grenoble, 14-18 March 2011.

T. Christen and Q. Huang, “A 0.13um CMOS 0.1-20MHz Bandwidth 86-70dB DR Multi-Mode DT Delta-Sigma ADC for IMT-Advanced”, Proceedings of the 2010 European Solid-State Circuits Conference (ESSCIRC 2010), pp. 414-417, Sevilla,Spain, Sept. 2010.

C. Enz and A. Kaiser, Editors, MEMS-based Circuits and Systems for Wireless Communication, Springer, to be published in 2011.

M. Contaldo, D. Ruffieux, and C. Enz, “A 5.4dBm 42mW 2.4GHz CMOS BAW-based Quasi-Direct Conversion Transmitter,” Int. Solid-State Circ. Conf. Dig. of Tech. Papers, pp. 498-499, Feb. 2010.

B. Banerjee, C. Enz, and E. L. Roux, “Detailed Analysis of a Phase ADC,” IEEE Int. Symp. on Circuits and Syst. (ISCAS), pp. 4273-4276, June 2010.

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QCryptSecure high-speed communication based on quantum key distribution

Phot

oxpr

ess

PrinciPal investigator

Prof. Nicolas Gisin, uniGE

co-aPPlicants

Prof. Andreas P. Burg, EPFL

Prof. Norbert Felber, ETHZ

Prof. Etienne Messerli, HEs-sO

Dr. Grégoire Ribordy, IDQ

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QCryptsECuRE HIGH-sPEED COMMuNICATION BAsED ON QuANTuM KEY DIsTRIBuTION

GoalsToday’s information society relies heavily on storing and transferring data in digital form. Cryptography provides the means that is necessary to exchange data securely. It relies on two fundamental parts: first, one needs a secret key, which is subsequently used to encrypt the data with a mathematical algorithm. Secret keys can be transmitted using a trusted messenger, or in a more convenient way, using public key infrastructure, the security of which is based on computational complexity and suffers from the lack of a mathematical proof for the class of complexity. Modern encryption, using algorithms like the Advanced Encryption Standard, is generally considered unbreakable, provided the keys are sufficiently long. However, absolute security can only be guaranteed by the so-called one-time-pad (OTP), where secret keys as long as the message, have to be used.

This project aims to considerably improve cryptography on both the key distribution level and the encryption level. Quantum Key Distribution (QKD) is a secure way to generate and distribute keys, which is based on the fundamental laws of quantum mechanics. However, existing systems are too slow. The new QKD system will be capable of producing keys at 1 Mbps rate, which means it will allow 1 MHz OTP encryption for high-level applications.

In standard applications the data exchange rates continue to increase. Today’s commercial encryptors are already approaching 10 Gbps. Consequently the project seeks to develop a future proof encryption engine for up to 100 Gbps and looks to combine this high-speed encryption with high rate QKD, to allow the rapid changing of keys, thus considerably improving the security and simplifying the key management.

The project will develop advanced prototypes for very-high-speed QKD and encryption. Both of these systems will greatly surpass any technology currently available. This is only possible by combining the outstanding competencies of the partners in such diverse fields as quantum optics, high-speed electronics and integrated circuit programming as well as cryptographic and network security. The modular approach will provide flexible solutions for diverse communication scenarios by operating the devices in unison or stand-alone. Finally, in contrast to current quantum key distribution systems, they will be compatible with standard optical networks and capable of using wavelength multiplexing.

Cryptography: crucial to security in information transfer!

Quantum key distribution:Secure way to generate keys, based on fundamental laws of quantum mechanicsCurrently too slow!

Goal: Develop High-speed Quantum Key Distribution Key production at 1 Mbps rate

ENCRYPTIONData throughput so far limitedto 1 Gbps (possibly 10 Gbps)Goal: develop a future proof encryption engine for up to 100 Gbps

Initially focus on 40 Gbps system rates andon-board processing engine at 100 Gbps

KEY DISTRIBUTION2 mainsaspects:

Combine high-speed encryption with high-rate quantum key distribution

Fast Encryption System Fast Encryption System

QKD System (user A) QKD System (user B)

Public fiberNetwork

Moreover…• compatibility with standard optical networks• ability to use wavelength multiplexing

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ContextThe QCrypt approach is novel in the sense that it is, to the team’s knowledge, the only one developing both advanced QKD and encryption system to work together. It can also be stated that either system is at the cutting edge in its own right. The QKD system is designed for high-speed and is based on the COW protocol developed in Geneva. This is one of the leading practical QKD schemes and the Qcrypt team is the only group developing it as other groups are working on different protocols based on their own proprietary knowledge. The rates that QCrypt has achieved so far are similar to the minimum expected performance which is targeting. The consortium has also been developing dedicated single photon detector technologies –the fastest gated-mode detectors in the world have recently been achieved. As such we are very optimistic to outperform most practical systems in terms of secret key yield.

Forward error correction for QKD has been investigated theoretically and different strategies have been proposed. Previous information theoretic investigations have targeted long block lengths. In this work, complexity-related design criteria have been defined. Based on these criteria it was found that codes based on such criteria can also perform well under practical constraints. Initial complexity estimates indicate that implementation of corresponding decoders with the required throughput is indeed possible with reasonable complexity and storage requirements.

Commercial high-speed encryption systems go up to 10 Gbps. Research records for AES encryption reach 500 Gbps, which is achieved by squeezing as many AES cores into a large FPGA, and performed without authentication. The QCrypt approach is unique in the sense that it includes – besides 100 Gbps encryption and authentication – the adaptation of the data stream to the fast optical transceivers, and a seamless interface to the QKD system for high rate secure secret key exchange. For the secure link, it will allow (expensive) long distance 100G fibre connection or (relatively cheap) short distance 100G “active cable”. On the user side, a configurable mix of common 1G and 10G interfaces, and also 100G “active cable” options will be offered.

ResultsAfter having finalized the project specifications and the Preliminary Security Report, the centre-piece of the project deliverable has been successfully built, upon which the last stages can be easily built.

The Quantum Optics Layer is in the course of being assembled, and there is first experimental data feedback. Similarly, the Electronics Layers and the Optical Service Channel approach finalisation.

Furthermore, the computer, which manages the QKD, has been fully specified. A prototype 100Gb/s encryptor is now available, and the team has been able to test the implementation of the unicast traffic encryption as well as Key Management and Network Functions.

Among other significant facts related to the QCrypt project:

- The University of Geneva has filed a patent: US-Patent No. 13/182311. “Apparatus and method for distributing a string of secret bits over a quantum channel”. Hugo Zbinden, Nino Walenta, Charles Ci Wen Lim.

- The ETHZ partner is preparing a patent application on new methods for the realization of physically unclonable functions

G. Ribordy and P. Trinkler have presented some results of the project in the Electrosuisse Bulletin, (Physique quantique et cryptographie production et distribution sécuritée de clés cryptographiques, electrosuisse, Bulletin 7, 27-31, 2011)

Results presented in other specialized media include :

- E. Messerli, O. Auberson, Révolution dans la cryptographie quantique, Newsletter Alliance N°3 Infocom, 28.10.2011; Accepted

- E. Messerli, O. Auberson, Y. Graf, Quand la lumière sécurise davantage les réseaux, Swiss Engineering RTS N°10, 11.10.2011; Accepted.

- E. Messerli, O. Auberson, Révolution pour le très haut débit, Market.ch, N°91, Sept 2011; Accepted.

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PublicationsL. Henzen, VLSI Circuits for Cryptographic Authentication, PhD Thesis ETH-No. 19351, Published in Series in Microelectronics, Volume 214, Hartung-Gorre Printing House, Konstanz, Germany, 2011, ISSN 0936-5362, ISBN 978-3-86628-367-1.

L. Henzen, W. Fichtner, FPGA Parallel-Pipelined AES-GCM Core for 100G Ethernet Applications, Proc. of IEEE ESSCIRC, Sevilla, Spain, Sep 2010.

J.P. Aumasson, L. Henzen, W. Meier, M. Naya-Plasencia, Quark: A Lightweight Hash, Proc. of Workshop on Cryptographic Hardware and Embedded Systems (CHES), Santa Barbara, CA, USA, Aug 2010.

L. Henzen, P. Gendotti, P. Guillet, E. Pargaetzi, M. Zoller, F.K. Gürkaynak, Developing a Hardware Evaluation Method for SHA-3 Candidates, Proc. of Workshop on Cryptographic Hardware and Embedded Systems (CHES), Santa Barbara, CA, USA, Aug 2010.

Luca Henzen: “VLSI Circuits for Cryptographic Authentication” Dissertation ETH No. (tbc) - This will also be published in: Series in Microelectronics, edited by Wolfgang Fichtner, Qiuting Huang, Heinz Jäckel, Gerhard Tröster & Bernd Witzigmann, Hartung-Gorre Verlag Konstanz.

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SelfSysFluidic-mediated self-assembly for hybrid functional micro/nanosystems

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PrinciPal investigator

Prof. Jürgen Brugger, EPFL

co-aPPlicants

Dr. Helmut Knapp, CsEM

Prof. Alcherio Martinoli, EPFL

Prof. Bradley Nelson, ETHZ

M.sc. Laurent sciboz, Icare

Prof. Nicholas spencer, ETHZ

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SelfSysFLuIDIC-MEDIATED sELF-AssEMBLY FOR HYBRID FuNCTIONAL MICRO/NANOsYsTEMs

GoalsPackaging and assembly is a key factor in the commercial success of micro/nanosystems (M/NEMS), but it is often neglected in academic and pre-competitive industrial research and development. A lack of innovative solutions for the manufacturing of next-generation smart systems with hybrid, multi-functional devices would hamper the advances that are needed in health care, information technology and environmental engineering. For instance, a typical situation today is that the individual components of the hybrid system can be readily fabricated separately by well-known state-of-the-art methods, but they are either too small or too numerous to be assembled using conventional assembly techniques. The solution studied in this project is based on interaction forces in liquids and goes well beyond what is known today as fluidic self-assembly on surfaces using wetting properties to fine-position MEMS parts.

The ultimate goal is to self-assemble free-floating N/MEMS building blocks in a liquid, and then deploy the assembled parts onto substrates, in the environment or in the human body, where they fulfill an application-specific functionality. This fluidics-based self-assembly forms the basis for future manufacturing of intelligent systems beyond robotic assembly. The expected outcomes are cost-efficient yet flexible, and form an exemplary combination of high numbers (tera) of ultra-small components (nano/micro) to be assembled into complex systems. The project involves an intimate interaction between advanced micro/nanoengineering, surface functionalization, microfluidics, sensing/actuation, micro/nanorobotic and model-based design concepts.

The first phase of the research focuses on the setting-up of the free-floating and guided fluidic assembly technology. The work will then be devoted to the implementation of the enabling technology for two applications that have been identified, one targeting the assembly of liquid-containing micro-capsules that can be triggered for liquid release, the other aiming at the assembly of RFID micro-tags with other M/NEMS in a massive parallel way. In general, such integrated systems can enable non-invasive smart drug delivery devices, self-assembling implants, surgical microrobots, smart clothing, ultra-small wireless sensor nodes for environmental monitoring and proactive maintenance of complex civil and mechanical structures.

need to find novel, low cost processes to assemble and integrate complex micro-objects into large networks in a massively parallel manner

Basic freeself-assembly

CASE STUDIES

Self-assemble N/MEMS components as they are fully immersed in a liquid possibility to encapsulate the functional liquid

Alternate assembly inmicrofluidic channels

Assembly of MEMSto micronscale RFID tag for subsequent MEMS tracking

Assembly ofliquid-containingmicro-capsulesthat can be triggeredfor liquid release

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ContextSelfSys's on-going research on microfluidic self-assembly of heterogeneous M/NEMS structures clearly emerges among international, competitive research trusts. In fact, it is grounded on a tight feedback between experimental (i.e., design and machining of microcomponents, assembly processes) and theoretical (i.e., modeling and control) investigations into the variety of aspects characterizing its deployment. Importantly, the design and directed aggregation of microstructures is conceived within a control-oriented, multi-level modeling framework which draws from and extends the established knowledge and experiences matured in distributed robotic systems. A fundamental aim of this project consists in the demonstration that model-based design, engineering and control of self-assembly processes - which is currently successfully performed through centimeter-sized mechatronic components - is not only feasible but even advantageous also for the fluidic self-assembly of M/NEMS. The expected advantages concern performance, resource exploitation, flexibility and adaptation to a variety of target structures.

ResultsThe MEMS fabrication of the micro capsules has made considerable progress in terms of shape control and surface properties. The material and surface properties of the polymer devices have been further functionalized for enhanced control of interfacial forces. Improved microfluidic handling and mixing system, together with live video tracking system has been implemented and validated. External control via magnetic forces shows interesting characteristics, promising for further controlling the assembly process. Modeling of self-assembling systems is improving and progressing as rapidly, and it is continuously validated with physical experiments to further fine-tune the simulations.

Among significant facts related to the SelfSys project:

- One patent has been filed based on knowledge developed prior to the project, entitled “Containers assembled in fluid and corresponding production” (J. Brugger, A. Martinoli, G. Mermoud, C. Martin-Olmos). The invention consists in the fabrication of half containers that can be assembled in fluid, liquid and/or gas, hence, when the half pieces meets and form the capsule, some amount of their floating environment is trapped inside. This opens the possibility to release the fluid trapped later on.

- A best poster award was obtained for the poster “Fabrication of polymeric micro structures by controlled drop on demand inkjet printing “ by L. Jacot-Descombes, M. Gullo, V. Cadarso, J. Brugger, presented at the Micromechanics and Micro systems Europe workshop (MME) 2011: This price (Gold award) awarded with 150 euros the best poster presented at the workshop.

PublicationsL. Jacot-Descombes, M. R. Gullo, V. J. C. Busto, J. Brugger, Fabrication of Polymeric Microstructures by Controlled Drop on Demand Inkjet Printing, 22nd Micromechanics and Micro systems Europe Workshop, Toensberg, Norway, 2011, Best Paper Award.

M. R. Gullo, L. Jacot-Descombes, L. Aeschimann and J. Brugger, Characterization of Hydrophobic Forces for in Liquid Self-Assembly of Micron-Sized Functional Building Blocks. Mater. Res. Soc. Symp. Proc. Vol. 1299, 2010.

M. Mastrangeli, G. Mermoud, A. Martinoli, Modeling self-assembly across scales: The unifying perspective of Smart Minimal Particles, Micromachines 2 (2), Special Issue on Self-Assembly, 82-115 (2011).

G. Mermoud, U. Upadhyay, W.C. Evans, and A. Martinoli, “Top-Down vs Bottom-Up Model-Based Methodologies for Distributed Control: A Comparative Experimental Study”. Proc. of the Twelfth Int. Symp. Experimental Robotics, December 2010, New Delhi, India, Springer Tracts in Advanced Robotics (2011), to appear.

E. Di Mario, G. Mermoud, M. Mastrangeli, A. Martinoli, A trajectory-based calibration method for stochastic motion models, Proc. of the IEEE/RSJ Int. Conf. on Intelligent Robots and Systems, San Francisco, U.S.A., September 2011, to appear.

M. Suter, O.Ergeneman, J.Zürcher, C.Moitzi, S.Pané, T.Rudin, S.E. Pratsinis , B.J.Nelson, C.Hierold, A photopatternable superparamagnetic nanocomposite: Material characterization and fabrication of microstructures, Sens. Actuators B: Chem. 156, 1, 2011.

D. Xu, K. Shou, B. J. Nelson, Dielectrophoretic assembly of carbon nanotube-based NEMS devices using floating electrodes, Microelectron. Eng. 88, 8, 2011.

M. Suter, O. Ergeneman, J. Zürcher, S. Schmid, A. Camenzind, B. J. Nelson and C. Hierold, Superparamagnetic photocurable nanocomposite for the fabrication of microcantilevers, J. Micromech. Microeng. 21, 2011.

G. Mermoud, L. Matthey, W. C. Evans, and A. Martinoli, Aggregation-mediated Collective Perception and Action in a Group of Miniature Robots, in Proceedings of the 9th International Conference on Autonomous Agents and Multiagent Systems (AAMAS-2010) (W. van der Hoek, G. A. Kaminka, M. Luck, and S. Sen, eds.), 2010, pp. 599-606. Nominated for CoTeSyS Best Robotics Paper Award.

W. C. Evans, G. Mermoud, and A. Martinoli, Comparing and Modeling Distributed Control Strate- gies for Miniature Self-Assembling Robots, in Proceedings of the 2010 IEEE International Conference on Robotics and Automation (ICRA 2010), 2010, pp. 1438-1445.

G. Mermoud, A. Prorok, L. Matthey-de-l'Endroit, C. Cianci, A. Martinoli, Self-Organized Robotic Systems: Large-Scale Experiments in Aggregation and Self-Assembly using Miniature Robots, Handbook of Collective Robotics, 2011, to appear.

G. Mermoud, M. Mastrangeli, U. Upadhyay, A. Martinoli, Real-Time Automated Modeling and Control of Self-Assembling Systems, Proc. of the 2012 IEEE Int. Conf. on Robotics and Automation (ICRA 2012), St.Paul (MN, USA), May 2012, to appear.

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Add-on: SelfSys+ FLuIDIC-MEDIATED sELF-AssEMBLY FOR COMPLEx, HYBRID FuNCTIONAL MICRO/NANOsYsTEMs

PrinciPal investigator Prof. Jürgen Brugger, EPFL co-aPPlicants Prof. Christofer Hierold, ETHZ Dr. Helmut Knapp, CSEM Prof. alcherio Martinoli, EPfL Prof. Bradley Nelson, ETHZ Prof. Dimos Poulikakos, ETHZ M.Sc. Laurent Sciboz, icare Prof. Nicholas Spencer, ETHZ Prof. John Thome, EPfL

The SelfSys consortium recently identified additional mechanisms to enhance the self-assembling of MEMS capsules as envisioned in SelfSys that would further enhance both our scientific content and application spectrum. Adding them to the ongoing activities increases on one hand side the success rate of our chosen approach and secondly, it integrates other research groups with complementary skills recently uncovered.

The central part of the add-on activities involves the controlling of mutual interaction among self-assembling micro capsules inside a liquid. The project seeks to activate following three key features that affect their fabrication and conditioning: directionality, i.e. anisotropy, selectivity, i.e. distinction between interaction and component types, as well as reversibility including programmability.

To this end, additional schemes that are complementary and fully compatible with the technologies already matured in SelfSys are planned:

a) long-range attraction and local heating by magnetic particles embedded in a 3D structured polymer, b) selective deposition of curable polymer on target patterns on capsule surface by a novel fabrication technique called iLEM.

These additions involve physical interactions dominating at nanoscale (i.e. magnetic nanoparticles, tunable surface tension, and local heat generation) and will increase the success rate for robust assembly. it will furthermore make the process readily suitable for upscaling in dimension and structural complexity (i.e. for the assembly of heterogeneous components into non-trivial spatial patterns of enhanced functionality).

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SImOSSmart implants for orthopaedics surgery

PrinciPal investigator

Prof. Peter Ryser, EPFL

co-aPPlicants

Prof. Kamiar Aminian, EPFL

Dr. Catherine Dehollain, EPFL

Prof. Pierre-André Farine, EPFL

Prof. Brigitte Jolles-Haeberli,

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M.sc. vincent Leclercq, symbios

Prof. Philippe Renaud, EPFL

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SImOSsMART IMPLANTs FOR ORTHOPAEDICs suRGERY

GoalsOver one million hip and knee prostheses are implanted each year in the EU and the US. The expected lifetime for these prostheses is between 10 and 20 years, but premature failure is quite common (about 20% for people less than 50 years old). Prosthesis failures require revision surgeries that are generally complex and traumatic. None of these prostheses contain microchips and few are analyzed based on motion analysis devices.

This project seeks to design innovative tools to measure in vivo biomechanical parameters of joint prostheses, orthopaedic implants, bones and ligaments. These tools, partly implanted, partly external, will record and analyze relevant information in order to improve medical treatments. An implant module includes sensors in order to measure the forces, temperature sensors to measure the interface frictions, magneto-resistance sensors to measure the 3D orientation of the knee joint as well as accelerometers to measure stem micro-motion and impacts. An external module, fixed on the patient’s body segments, includes electronic components to power and to communicate with the implant, as well as a set of sensors for measurements that can be realized externally.

This equipment is designed to help the surgeon with the alignment or positioning phase during surgery. After surgery, by providing excessive wear and micro-motion information about the prosthesis, it will allow to detect any early migration and potentially avoid later failure. During rehabilitation, it will provide useful outcomes to evaluate in vivo joint function. The tools provided can also be implanted during any joint surgery in order to give the physician the information needed to diagnose future disease such as ligament insufficiency, osteoarthritis or prevent further accident. The proposed nanosystems are set to improve the efficiency of healthcare, which is both a benefit to the patient and to society. Although the scientific and technical developments proposed in this project can be applied to all orthopaedic implants, the technological platform which is being built as a demonstrator is limited to the case of knee prosthesis. In addition, by reaching the minimum size achievable thanks to clever packaging techniques and also by reducing, or even removing, the cumbersome battery, it paves the way for a new generation of autonomous implantable medical devices.

Joints implanted in EU & US: > 1 million/year

Expected to last 10-20 years… but frequent premature failure (~20% for people younger than 50)

complex, costly & traumatic revision surgery needed

Goal: Design innovative tools (implanted & external) to monitor in vivo biomechanical parameters of joint prosthesis & orthopaedic implants

useful… • during surgery – for alignment/positioning phase • after surgery – to detect early migration • during rehabilitation – to evaluate joint function

ADJUSTABLE TO ALL PROSTHESESCurrently: prostheses with implants must be custom-made

Resorting to nano-scale elementswill not affect the mechanical properties

System adaptable to any prosthesis for a better flexibility

WITH ORIENTATION SENSORSBeside force sensors, the prosthesis willalso include orientation sensors.

Subtle combination of parameters frominternal sensors (that need little power)and external sensors

FRICTION & LOOSENING PREVENTION

More sensors can be included:• Temperature sensors to measure friction and wear• Accelerometers in order to prevent prothesis loosening

Innovative features:

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ContextThere are a few works in the area of instrumented prostheses and they mainly focused on measuring forces applied on the prosthesis during different movements.

One of the pioneers is the biomechanics laboratory of Charité-Universitätsmedizin Berlin. In 2007 they implemented a tibial tray for measuring the six load components in total knee arthroplasty, in which they placed strain gauges in the tibial part of the prosthesis. They also studied the components of contact forces and moments of knee prosthetic joint in five subjects performing different activities in 2010. Another team, from Scripps Clinic (San Diego, USA), designed an implantable telemetry device for this purpose in 2005; they put the strain gauges in the tibial plate as well. The instrumented prosthesis designed by their team was also implanted in three subjects and has measured the forces in vivo during different exercises in 2008.

Providing such in vivo force measurement has an invaluable outcome for research purpose, however these instrumented knees have been implanted only on few patients. The main reason is that the electronic components are inserted in the metal part involving a custom design of the prosthesis. Electronic components and sensors cannot be inserted in any prosthesis without completely redesign of the implant. Moreover the sensors only measure force components, and do not provide any information about the kinematics. The study is only valid and accurate for the used prosthesis and cannot be generalized to all different prostheses. In contrast, a new force sensor was designed for in vivo measurements of dynamic and static forces in knee prosthesis by Crescini et al. in 2011, in which the sensors and electronic components were positioned inside the polyethylene part of the implant.

The originality of the SImOS project is multifold. First, the objective is not only to measure force and motion signals for biomechanics research as other cited groups, but also to provide metrics based on these measurements which can be beneficial for the clinicians and prosthesis designers. For example, the original design of the strain gauge sensors allows extracting force information, which express wearing of the prosthesis or features capable to detect the unbalanced ligaments after surgery. Second, the measurements are not limited to internal forces but also include the measurement of 3D joint angles, translational movements, and prosthesis-bone micro-motions. Third, the aim is to fuse both implanted sensors and wearable sensors to enhance the accuracy of the measurement parameters.

The effort will be oriented to integrate all electronics in polyethylene part, offering in this way a wide range of prosthesis to be instrumented by only adapting the simple polyethylene part.

ResultsAt the present state of the project, the final version of the large-scale demonstrator of the SImOS system has been designed. It is based on commercially available components and miniaturization is not the focus. Its goal is to prove the concept of measuring the biomechanical parameters of interest of the F.I.R.S.T. knee prosthesis, provided by the industrial partner Symbios SA.

In particular, it will enable measures of the force applied on the prosthesis (both the total force and the balance between the two condyles) and of kinematics parameters such as 3D joint angles, translational movements or prosthesis-bone micro-motions. For force measurements new strain gauges have been designed and fabricated, while for kinematics measurements commercial magnetic sensors and accelerometers have been used. An analog front-end has been designed to interface the analog sensors and a system based on a microcontroller will manage the data acquisition and the transmission to a reader, by a Passive Low-Frequency RFID Transponder Interface, that will be used also to power supply the system.

The SImOS project has motivated the expansion of the so far developed "smart" technology towards other applications. One was to start the development of "smart" artificial spinal disc by utilizing the same approach taken in the SImOS project. The project succeeded and it will likely help companies to improve their designs of artificial spinal discs.

Another success branched from the SImOS project was the development of a “smart” distractor for knee arthroplasty. Force sensors were embedded in the distractor and the team believes it can be of great help for surgeons to improve the knee balance during a knee arthroplasty.

Among significant facts related to the SImOS project:

- In the Prime conference in 2011, the authors are recognized to silver leaf certificate for the paper “FoM to Compare the Effect of ASK Based Communications on Remotely Powered Systems”.

- Swiss Romande TV (TSR) has realized a special reporting dedicated to knee replacement surgery. CHUV-DAL, EPFL-LMAM and Symbios SA, participated to this program by reporting different aspects of knee replacement, knee prosthesis design and outcome evaluation of knee replacement. This reporting entitled “Mal au genou: on change tout!” was broadcasted on TSR1 television in program “36,9” on October 6th 2010.

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PublicationsA. Arami, M. Simoncini, O. Atasoy, W. Hasenkamp, S. Ali, A. Bertsch, E. Meurville, S. Tanner, H. Dejnabadi, V. Leclercq, P. Renaud, C. Dehollain, P.A. Farine, B.M. Jolles, K. Aminian, P. Ryser, “Instrumented prosthesis for knee implants monitoring”, 2011 IEEE Conference on Automation Science and Engineering (CASE), August 24-27 2011, p. 828-835.

S. Ali, S. Tanner, P.A. Farine, “A robust, low power, high speed voltage level shifter with built-in short circuit current reduction”, 2011 20th European Conference on Circuit Theory and Design (ECCTD), August 29-31 2011, p. 142.145.

A. Arami, H. Dejnabadi, V. Leclercq, K. Aminian, “An Implantable System for Angles Measurement in Prosthetic Knee”, presented at the International Society of Biomechanics (ISB), Brussels, Belgium, July 3-7, 2011.

E.G. Kilinc, O. Atasoy, C. Dehollain, F. Maloberti, “FoM to compare the effect of ASK based communications on remotely powered systems”, 2011 7th conference on PhD Research on Microelectronics and Electronics (PRIME), July 3-7 2011, p. 29-32.

Add-on: SImOS+ KNEE sIMuLATOR

PrinciPal investigator Prof. Peter Ryser, EPFLco-aPPlicants Prof. Kamiar Aminian, EPFL Dr. Catherine Dehollain, EPfL Prof. Pierre-andré farine, EPfL Prof. Brigitte Jolles-Haeberli, CHuV M.Sc. Vincent Leclercq, Symbios Prof. Philippe renaud, EPfLindustrial partner Symbios SA

During the first year of SimoS project, the consortium designed a first version of the large scale demonstrator in which inertial sensors were integrated, strain gauges and conditioning electronics which will be consequently capsulated into the prosthesis. The team also provided a wireless communication and power transmission between the implanted sensors and electronics, and the receiver part outside the prosthesis. Therefore the project reached the point that it is in serious need for validating all the designed sensory parts as well as the algorithms in conditions close to in-vivo. one solution as described in the SimoS proposal extends this first prototype to a simple motorized version where kinematics and force are controlled with one or two degree of freedom. in this case, the simulator can be used as a large scale demonstrator for different parts of the project but will have many limitations such as restricted degree of freedom, impossibility to fix artificial or cadaveric limb or simulate soft tissue artifact.

A much robust and global solution to validate the systems and to demonstrate the project’s results is to use a commercial mechanical simulator of knee. The simulator must have the capability to move in a similar way of the human knee, and provide the realistic axial forces. This simulator can play an integral role to make us sure that the best system with minimal configuration will be implanted on the patients.

using this simulator can also provide valuable documentary and articles from the project works, which can be more meaningful and useful for prosthesis designers, clinicians, and other researchers.

Therefore, the add-on funding plan is to purchase a MTS 858.20 system for kinematic knee testing.

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TecInTexTechnology integration into textiles: empowering health

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PrinciPal investigator

Prof. Gerhard Tröster, ETHZ

co-aPPlicants

Dr. Manfred Heuberger, EMPA

M.sc. Jean Luprano, CsEM

Dr. stéphanie Pasche, CsEM

Dr. René Rossi, EMPA

Prof. Martin Wolf, usZ

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TecInTexTECHNOLOGY INTEGRATION INTO TExTILEs: EMPOWERING HEALTH

GoalsFuture personal mobile systems consist of a communication and computing hub – e.g. a Smart Phone – which ensures the continuous and online connectivity. The personalization of this communication node requires the connection to sensing capabilities close to the human body, which detect the user’s context, be it the activity, motion, health or the mental and social behavior. In that spirit, an increasing variety of wearable functionality is being developed and demonstrated worldwide. However, in the textile sector, the actual breakthrough of these novel technologies is absent due to a general lack of compatibility of conventional electric, electronic and sensory devices with textile processing procedures and textile wearability. Indeed, existing e-textiles usually integrate state-of-the-art electronic devices into clothing, inducing many limitations like restricted flexibility, washability and comfort.

TecInTex addresses these issues by developing the necessary basic fiber and textile technology, at the nanometer and micrometer scale, that will provide the highly needed full integration of novel functionalities into truly wearable clothes without compromise on textile properties. The key elements include electronic and optical fibers, sensor yarns, transducers between electrical and optical signals, sensor stripes and functionalized fabrics.

The expected results cover a family of new sensorized and functional fibers, which will allow in situ measurements of body functions and biological species in body proximity, approved fabrication processes and working prototypes dedicated to health care, rehabilitation and prevention. One tremendous and growing market for these textiles is health care. Two demonstrators for wearable biosensing will be developed under the leadership of the Swiss Paraplegic Center and the University Hospital of Zurich. The TecInTex mission will be concentrate specifically on two demonstrators in the health care domain. The active NIRS sock is a wearable near infrared spectroscopy device which allows to monitor tissue oxygenation in the muscle continuously and non-invasively for the early detection of peripheral vascular disease. Another application is the intelligent underwear for paraplegic people, which allows the detection of pressure ulcers, an open skin lesion affecting bed-ridden patients.

Sensing capabilities close to the human body monitor activity, motion, health…

Incorporate built-in technological elements in our everyday textiles & clothes

Existing E-textiles: low processability, wearing comfort, washability…

Goal: get the crucial core modules to design & manufacture truly wearable functional clothes

• electronic fibers point-to-point connection inside the fabrics• optical fibers sensitive to changes in the contacting liquid env. (bio-sensing appl.)• sensor yarns & stripes• transducer between optical & electrical signals

ACTIVE NEAR INFRARED SPECTROSCOPY SOCK INTELLIGENT UNDERWEAR FOR PARAPLEGIC PEOPLE

Peripheral vascular disease affects 30% of adults

Early detection possible by near IR spectroscopy,but conventional sensors are cumbersome

Light wearable system in sock to monitor tissue oxygenation continuously & non-invasively

Pressure ulcers:big problem of paraplegic and bed ridden patients

Build a comfortable device to detect the risk for pressure ulcers in order to enable preventive measures

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ContextAt the Avantex Symposium and the Techtextil Symposium (May 2011, Frankfurt), several research groups presented projects regarding integration of electronic functions. Besides our e-fibers, conductive yarns based on other concepts are under development: non isolated nanoscale metal oxide coatings (NC State University) or conductive CNT coatings (FP7 programme “UV-Tubes: UV-curable yarn finishing with carbon nanotubes to obtain yarns with good permanency of conductive properties”, presented by Centexbel). In comparison to these developments, TecInTex’s e-fibers profit of the excellent washfastness of the metallic coating, the insulation and the good conductivity. In the absence of a real conductive yarn, people used, e.g., thin, laquered copper wires, PA yarns with a galvanic silver coating (1 micrometer Ag, sol-gel SiOx insulation under development), copper foils on PU sheets, yarns having stainless steel filaments, or just conventional electrical wiring.

Optical fibers for sensing are mostly used for non-invasive measurement. Here, sensing optical fibers allow detecting changes in liquid, and, with the development of a sensing chemistry for proteases, go beyond physico-chemical measurements, such as pH. In addition, the use of flexible optical fibers will enable using the sensor for on-body applications.

Literature and patent search confirm that no research group deals with the development of textile polymeric optical fibers.

TFTs and circuits on flexible substrates are fabricated also by other researchers, but the influence of mechanical strain is nearly not investigated. The integration of flexible sensors into textiles was not performed by other groups to our knowledge.

To the best of the consortium’s knowledge, TecInTex is the only project working on including optical near-infrared spectroscopy sensors into textiles. Other groups have more bulky separate sensors, which are often uncomfortable and difficult to attach. TecInTex’s approach provides a comfortable and reliable attachment to the body.

ResultsRecent research in the TecInTex project is characterized by the step-by-step exploitation of the basic material research results towards the first generation of functional fabrics and yarns available for fabrics experiments.

The team has successfully developed nano-micron protective and insulation coatings for the metallized e-fibers. These coatings can be selectively stripped-off for interconnection to ICs and sensors.

Piezoresistive fibres have been successfully integrated in woven textiles achieving similar sensor properties in comparison to single fiber. Bi-component polymeric optical fibers have been manufactured using a melt-spinning process. Flexibility and mechanical stability qualify these fibers for application in the standard textile manufacturing processes like weaving, stitching, knitting.

Optical fibers for biosensing have been developed for pH and protease activity detection. A first prototype has been designed, including connections, electronics and signal processing.

Amorphous InGaZnO TFTs and circuits, as well as different gas and humidity sensors have been fabricated on flexible substrates, and experiments regarding the influence of mechanical strain have been performed.

Among significant facts related to the TecInTex project:

- A patent application is in preparation: “Method for producing electro-conductive multiple-pole (multiconductor) fibers”.

- A European patent on the sensing chemistry for the detection of protease activity (WP3) has been prepared and filed on September 2, 2011: B. Schyrr, S. Pasche, G. Voirin, CSEM SA, Dye-doped gelatin-coated optical fibers for in situ monitoring of protease activity in wounds, EP11179927.

- Best poster award: International Symposium on Olfaction and Electronic Nose 2011 New York, USA: Thomas Kinkeldei, Christoph Zysset, Kunigunde Cherenack and Gerhard Tröster, “A Flexible Gas Sensor for the Integration into Smart Textiles”.

- Best paper award for “Weaving integrated circuits into textiles” at International Symposium on Wearable Computing 2010, October 2010, Seoul Korea.

- Best oral presentation award for “Weaving integrated circuits into textiles” at EMPA PhD Symposium 2010, EMPA Dübendorf.

The results of the project have been disseminated in general and specialized media:

- An article was published in Le Temps on February 23rd, 2011: “Pansements intelligents” (S. Pasche)

- IEEE Spectrum news publisehd an article (by Lucas Laursen) in May 2011 entitled “Optical Fiber Watches Wounds – Woven into a bandage, an experimental optical fiber could monitor healing” )

- A feature article was included in Electronics Letters (vol. 47) about the paper “Indium-gallium-zinc-oxide based mechanically flexible transimpedance amplifier” published in the same issue of Electronics Letters

- An article about smart textiles at ETH was published in the Neue Zürcher Zeitung (NZZ).

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Publications D. Hegemann, M. Amberg, B. Hanselmann, S. Guimond, E. Körner, “Nanostructured plasma coatings for medical applications”, in Biomaterials and Plasma Processing, eds. N. Dumitrascu, I. Topala, Editura Universitatii Alexandru Ioan Cuza, Iasi, Romania, 2011, p. 87-102. (book chapter)

B. Selm, E. Aslan Gürel, M. Rothmaier, R. M. Rossi, L. J. Scherer, “Optical Fiber Fabrics for Illumination and Sensorial Applications in Textiles”, J. Int. Mat. Sys. Struct. 21, 1061-1071, 2010.

Thomas Kinkeldei, Christoph Zysset, Kunigunde Cherenack and Gerhard Tröster, “A textile integrated sensor system for monitoring humidity and temperature,” in Proc. International Conference on Solid-State Sensors, Actuators and Microsystems 2011, 02025 (2011).

Niko Münzenrieder, Kunigunde Cherenack and Gerhard Tröster, “The Effects of Mechanical Bending and Illumination on the Performance of Flexible IGZO TFTs,” IEEE Transactions on Electron Devices 58, 2041-2048 (2011).

Niko Münzenrieder, Christoph Zysset, Thomas Kinkeldei, Kunigunde Cherenack and Gerhard Tröster, “A flexible InGaZnO based 1-bit SRAM under mechanical strain,” IEEE SCD 2011, accepted for publication (2011).

Thomas Kinkeldei, Niko Münzenrieder, Christoph Zysset, Kunigunde Cherenack and Gerhard Tröster, “Encapsulation for Flexible Electronic Devices,” IEEE Electron Device Letters, accepted for publication (2011).

C. Zysset, N.S. Münzenrieder, T. Kinkeldei, K.H. Cherenack, G. Tröster, Indium-gallium-zinc-oxide based mechanically flexible transimpedance amplifier, Electronics Letters 47, 691 – 692 (2011).

C. Zysset, T. Kinkeldei, N.S. Münzenrieder, K.H. Cherenack, G. Tröster, Integration method for electronics in woven textiles, accepted for publication in IEEE Transactions on Advanced Packaging.

K. H. Cherenack, C. Zysset, T. Kindelkei, MaterialsN. Münzenrieder and G. Tröster, “Wearable Electronics: Woven Electronic Fibers with Sensing and Display Functions for Smart Textiles”, Advanced Materials 22:45, 5071 (2010).

N. Woo, K. H. Cherenack, R. Spolenak and G. Tröster, ‘Designing micro-patterned Ti films that survive up to 10% applied tensile strain, Applied Physics A 100, 1, pp. 281-285 (2010).

K. H. Cherenack, T. Kinkeldei, C. Zysset and G. Tröster, ‘Woven thin-film metal interconnects,’ IEEE Electron. Dev. Lett. 12, 7, pp. 740-742 (2010).

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QuickTime™ et undécompresseur

sont requis pour visionner cette image.

X-SenseMonitoring alpine mass movements at multiple scales

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PrinciPal investigator

Prof. Lothar Thiele, ETHZ

co-aPPlicants

Dr. Jan Beutel, ETHZ

Prof. Alain Geiger, ETHZ

Dr. stephan Gruber, uZH

Dr. Hugo Raetzo, FOEN

Dr. Tazio strozzi, Gamma

Remote sensing

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X-SenseMONITORING ALPINE MAss MOvEMENTs AT MuLTIPLE sCALEs

GoalsRecent observed environmental changes as well as projections in the fourth assessment report of the Intergovernmental Panel on Climate Change shed light on likely dramatic consequences of a changing mountain cryosphere following climate change. Some very destructive geological processes are triggered or intensified, influencing the stability of slopes and possibly inducing landslides. Unfortunately, the interaction between these complex processes is poorly understood. This project addresses the key issues in response to such changing conditons: monitoring and warning systems for the spatial and temporal detection of newly forming hazards, as well as extending the quantitative understanding of these changing natural systems and our predictive capabilities.

It will develop dependable wireless sensing technology as a new scientific instrument for environmental sensing under extreme conditions in terms of temperature variations, humidity, mechanical forces, snow coverage as well as unattended operation that are needed for longterm deployment. This technology should integrate various sensing dimensions (such as pressure, humidity, crevice movements, high precision deformation and movements) in terms of sensing and processing and the idea is to extend the spatial scope from local (microscopic) measurements to large scale information derived from satellite radar remote sensing and fuse the resulting information to achieve an unparalleled degree of precision in space, time and accuracy. The new measurement technology developed can be used to advance applications in science and society: geophysical and climate-impact research as well as early warning against landslides and rock-fall.

Research and development of several advanced sensing technologies and their system-level integration via systems and software engineering lie at the core of the project. They include model-based design to ensure dependable operation in a highly resource-constraint setting, optimized use of harvested solar energy through energy-efficient algorithms and long-term reward maximization as well as multi-objective optimization of the multi-processor hardware platforms. Also crucial is research on advanced differential GPS sensing for high-precision movement detection and the development of sensor fusion algorithms combining different classes of sensors with high spatial granularity and satellite-scale X-ray images.

All these activities are guided by thorough geophysical modeling and simulation as well as by demands from early warning scenarios. The project has the clear objective to develop a technology demonstrator that integrates the new technologies into the application field.

Global climate change:

Destructive geological processes make slopes unstable,inducing landslides

Develop a monitoring & warning system for the spatial and temporal detection of newly formed hazards

Extend the quantitative understanding of these systems and predictive capabilities

• Develop dependable wireless sensor technology for environmental sensing under extreme conditions

• Integrate various sensing dimensions and scales

• Extend the spatial scope from local measurements to large-scale information (derived from IN-SAR satellite remote sensing)

• Applications: Geophysical and climate-impact research, Early warning against landslides & rockfall

RESEARCH AREAS• High precision GPS and synthetic- aperture radar (SAR) data processing

• Modular, reliable architectures for sensor data fusion

• Geophysical models across multiple scales and dimensions

MAIN GOALS OF THE RESEARCHRT

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ContextWith wireless sensor networks emerging over the last decade and impacting a large number of fields spurring large amounts of research work the time has now come to apply this knowledge in serious applications. To this date, most applications deployed have been of prototypical character, rather short-lived, impaired by severe performance constraints or deficiencies or situated in or within close proximity to the built environment. To this extent the X-Sense project has pioneered low-power and long-term environmental monitoring especially with respect to the hazardous environment and system lifetime. Most sensors used in sensor networks used in environmental monitoring are quite simple, such as thermistors, wind gages or soil moisture. In a few occasions more complex acoustic or seismic sensors have been used. To the best of the team’s knowledge, GPS has only been used for tracking mobile bearers, such as animals or vehicles, not static objects such as envisioned for this project. The combination of sensors across different scales, ground based point measurements, GPS-derived velocity vectors and both ground and space based imaging techniques will allow for unprecedented spatial and temporal resolution. This is important as the characteristics of the slopes measured are mostly not known and partly explorative instrumentation will generally require more points to be measured.

Terrain or construction deformation monitoring by GNSS is a technology which has been developed to highly performing systems, e.g. Leica Spider and GeoMoS. In many countries permanent GPS networks have been set-up as online reference for surveying purposes, see e.g. AGNES and SWIPOS by swisstopo. For these systems, normally, expensive dual frequency receivers are deployed. In these cases, the calculation strategy is based on differencing techniques, i.e. making use of differences of measurements between, at least, two receivers. In this project, however, kinematic station coordinates are computed at cm-level accuracy, using low-cost, single frequency differential GPS carrier phase processing techniques. The time series of 17 months of GPS data acquired within the current project shows the capability of the low-cost system to reliably determine station velocities in the order of 1.0 to 2.5 cm/day. It further allows detecting seasonal velocity variations, as well as inter-annual variations. Investigations are in progress to assess the correlation between the observed surface velocities and the driving processes, e.g. meteorological influences.

To enhance the spatial resolution, video tracking is taken into account as an additional method to measure movements. Over the last two years, several webcam observation platforms have been installed which deliver images of several rock glacier tongues on a relatively high sampling rate. Tests are made with single camera takings, where like in InSAR; one and two dimensions of the movement are not distinguishable. By combining these results with GPS data, it will be possible to resolve the missing components in optical or radar tracking.

Slope instability is a natural process in mountain areas and considered a hazard when endangering human infrastructure and life. Hazard assessment is currently based on learning from the past: from measurements, historical records or geomorphic evidence. Like other research of environmental hazards (e.g., flood risk) this is now challenged by climate change adding the problem of non-stationarity: The geographic patterns, probability-density functions and governing processes of the phenomena of interest are subject to a considerable trend. Because this limits the utility of statistical and process-based models alike, many approaches to hazard assessment (in e.g., science, practice, and jurisdiction) have to be rethought. In mountain areas the problem of non-stationarity is compounded by high lateral variability (making measurements more important AND more difficult) and by the non-linearity of the response of cryosphere phenomena to environmental change. The projects X-Sense and PermaSense prototype vital infrastructure to obtain distributed measurements needed for the partly exploratory investigation of cryosphere phenomena and their changes.

ResultsThe following main results have been achieved recently in the project:

- Installation of more than 50 sensors in the Mattertal area selected for the case study. The first prototype system is functioning and first data have been collected. These data are currently undergoing geophysical analysis and initial results have been published.

- New concepts to improve system reliability and data quality based on model-based design principles have been developed and published.

- The GPS data processing framework has been set up and the workflow is ready for project partners.

- Based on surveying and field site selection an initial understanding of the processes governing terrain movement in alpine environments has been attained. This understanding has been backed up by initial data retrieved from the field sites.

- The environmental simulation framework has been refined and validated and is now ready for use.

The data pipeline of X-Sense has been established in a first prototype, spanning all major system layers: Sensing and data acquisition, wireless low-power multi-hop data communication, base-station processing and long distance-communication, storage in GSN-database, data cleaning, data processing and visualization, geophysical research results. More than 50 sensors have been installed in the Mattertal area. This infrastructure will serve as a basis for further research in the context of natural hazard early warning.

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PublicationsM. Keller, M. Woehrle, R. Lim, J. Beutel and L. Thiele: Comparative Performance Analysis of the PermaDozer Protocol in Diverse Deployments, Proceedings of the Sixth IEEE International Workshop on Practical Issues in Building Sensor Network Applications (SenseApp 2011), IEEE, Bonn, Germany, October, 2011.

V. Wirz, P. Limpach, J. Beutel, B. Buchli and S. Gruber: Temporal characteristics of different cryosphere-related slope movements in high mountains, Proc. 2nd World Landslide Forum, Springer, Berlin, October, 2011.

S. Gubler, J. Fiddes, S. Gruber, M. Keller, Measuring and analysis of scale dependent variability of ground surface temperatures in alpine terrain, The Cryosphere 5, 431–443 (2011).

M. Keller and J. Beutel: Efficient Data Retrieval for Interactive Browsing of Large Sensor Network Data Sets, Proceedings of the 10th International Conference on Information Processing in Sensor Networks (IPSN 2011), ACM/IEEE, Chicago, IL, USA, April, 2011.

F. Ferrari, M. Zimmerling, L. Thiele, O. Saukh: Efficient Network Flooding and Time Synchronization with Glossy, Proceedings of the 10th International Conference on Information Processing in Sensor Networks (IPSN), ACM/IEEE, Chicago, IL, USA, April, 2011.

J. Beutel, B. Buchli, F. Ferrari, M. Keller, L. Thiele and M. Zimmerling: X-Sense: Sensing in Extreme Environments, Proceedings of Design, Automation and Test in Europe, 2011 (DATE 2011), Grenoble, France, March, 2011.

M. Dall’Amico, S. Endrizzi, S. Gruber, R. Rigon: An energy-conservative model of freezing variably-saturated soil, The Cryosphere 5, 469–484 (2011).

A. Hasler, S. Gruber, M. Font, A. Dubois: Advective heat transport in frozen rock clefts – conceptual model, laboratory experiments and numerical simulation, Permafrost and Periglacial Processes (2011, in revision).

D. Perler, A. Geiger, F. Hurter: 4D GPS water vapor tomography: new parameterized approaches, J Geod. DOI 10.1007/s00190-011-0454-2, Springer-Verlag 2011.

A. Villiger, A. Geiger, A. Widet, and U. Marti (2011), SWISS-4D II: Geodetic analysis of geodynamic deformations in Switzerland, in Swiss National Report on the geodetic activities in the years 2007 to 2011, edited by J. Mueller-Gantenbein, A. Widet, U. Marti, M. Rothacher, and P.-Y. Gilleron, Swiss Geodetic Commission, ISBN: 978-3-904880-26-0.

R. Mautz, D. Grimm, P. Limpach, S. Tilch, A. Geiger (2010) Bestimmung der Fließgeschwindigkeiten von Blockgletschern, Geomatik Schweiz 108, Issue 6, pp. 264-268, ISSN 1660-4458.

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Autoimmune chronic diseases are gaining increasing prevalence in our societies, and therefore require intensified efforts towards their effective treatment. Rheumatoid Arthritis (RA) is one such disabling disease, affecting synovial tissue of the joints, and resulting in loss of function and mobility. RA hits patients in their productive, working age, and it is characterized by a strong prevalence in women (~70%). Despite no cure existing, patients receive therapies during the active stage of the disease when inflammation peaks and symptoms become acute. Conventional treatments make use of drugs with heavy side effects. Acupuncture is used by an estimated 13 million Chinese people and received increased interest in the western world. it appears to control the symptoms of the disease and/or the conventional treatment’s side effects, which limit the applicability of the therapy and strongly debilitate the patients’ organism. With very limited exceptions, no molecular rationale for the efficacy of acupuncture is available to date. Although supported by the World Health organization for the treatment of RA, the use of acupuncture remains limited and the real effect on the disease based on scientific investigations remains largely unaddressed.

Therefore, given the tremendous potential benefits of acupuncture, this project aims to address the currently lacking in systematic and scientific evidence of the physical and molecular mechanisms acting behind this therapy, by combining of clinical and broad spectrum high-throughput (omic) biomolecular data (sampled in blood) as well as innovative tools (the intelligent needle) to acquire additional data during acupuncture practice in animal models (rats). The identification of the molecular bases of acupuncture has the potential to open to a whole new area of research, where the present approach (and improvements) can be extended to the study of other diseases, and the integration of acupuncture and pharmacology can be envisaged for the design of new, more efficient and effective therapies.

intelligent needles with wireless connection to internet for biophysical bases of acupuncture

i-Needle

Sensor network research should be supported by realistic experiments performed in wireless sensor network test-beds. This requires repetition of experiments to achieve statistical significance, and to allow researchers to verify results. However, mobility of objects, sensors, and base stations is difficult to implement and to repeat in a testbed.The Mobile Multi-Media Wireless Sensor Networks (M3WSN) project seeks to use real testbeds for experiments but emulate mobility of personal devices, sensors, and base stations. M3WSN aims to build an experimental research platform including both communication in wireless sensor networks and processing sensor data in cloud computing environments.

The target research platform is based on existing solutions developed and used in previous projects. in particular, the achievements of the Eu FP7 project, Wisebed (Wireless Sensor Network Testbed) will be used. The work performed in M3WSN will enhance the Wisebed platform by wireless mesh nodes to allow experiments with software running on both wireless mesh and sensor nodes. The VirtualMesh emulation engine, which only supports wireless mesh nodes until now, will be extended to wireless sensor nodes. This will allow to experiment with software on real sensor nodes, but mobility and wireless communication of sensor nodes will be emulated.The research platform will be used by researchers to support their experimental research work on mobile multi-media sensing. M3WSN is designing a scalable network architecture for mobile multi-media wireless sensor networks. it targets a multi-media sensor system for object detection and tracking based on steerable cameras that are triggered and steered based on discrete sensor data.

Moreover, M3WSN will explore how opportunistic forwarding can be used to support the delivery of multi-media sensor data, when sensors are mobile. M3WSN will investigate mobile base stations visiting sensors for collecting multi-media sensor data. in this case, energy consumption at the sensors should be decreased by minimizing the activation of the transceivers used for communication between sensors and base stations.

Mobile multi-media wireless sensor networks

M3WSN

PrinciPal investigator Dr. sandro Carrara, EPfL

Prof. Giovanni De Micheli, EPfLDr. Christine Nardini, Shanghai inst. for Biological Sciences

PrinciPal investigator Prof. Torsten Braun, uniBE

Liusheng Huang, uni of Science and Technology of China, Suzhou

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The main aim of this project is the development of novel and safe boron respectively nitrogen containing hydrogen storage materials with the help of nano-structures. Hydrogen is the ideal means of storage, transport and conversion of energy for a comprehensive clean-energy concept. The availability of a safe and effective way to store hydrogen reversibly is one of the major issues for its large scale use as an energy carrier. Hydrogen storage in solids offers a safe alternative to storage in compressed or liquid form. However, at present, no single material fulfilling all requirements is in sight. Amidoboranes and aluminium borohydride have high hydrogen content and release hydrogen at rather the low temperatures. However, these materials have been found emitting toxic and possibly explosive hydrogen containing species such as ammonia and diborane, which is a drawback for the reversibility of the materials and a severe safety issue. Efforts will be put to achieve the goal of not having toxic exhausted gas and to drive the kinetics and thermodynamic constraints of these systems toward technology application ranges.

The project involves synthesis, analysis and theoretical modelling. While in China the focus is laid on the synthesis of amidoboranes, in Switzerland the aluminium borohydride will be the material of choice. Various mechanical and chemical syntheses will be carried out aiming at nano structuring the materials.

Since the goal is to try to release pure hydrogen, decomposition experiments will be the main tool to check the effectiveness of the proposed system. An apparatus combining gravimetric and spectroscopic analysis detects the exhausted gas, giving the quantitative amount of the gaseous decomposition products, while structural analysis gives a picture of the changes in the samples upon hydrogen sorption. The experiments will be supported by theoretical modelling of the involved reaction paths in order to help the data interpretation and to provide an explanation of the mechanisms behind the decomposition reactions.

Nano-confinement of nitrogen and boron based hydrides

NaNiBo

in recent years there has been a growing interest in the use of surveillance cameras to prevent accidents and crime, promote security and safety, and monitor critical systems and traffic scenes. Surveillance systems can be found everywhere: in transport systems from taxis to trams, from small corner stores to large banks, from lonely footpaths to crowded streets and sport arenas. With the advent of closed circuit television (CCTV) the task of monitoring no longer requires a significant physical presence: the collective images from a large number of cameras may be monitored by “controllers” working in front of several monitors. Because human monitoring of surveillance video is a very labor-intensive task, however, there is growing interest in developing intelligent and automated surveillance systems.

This project aims to develop control algorithms to enable the automation of surveillance tasks for networks of cameras. The control problems of interest in this context involve both continuous decisionmaking (selecting the pantiltzoom inputs for the cameras) and discrete decision-making (e.g. the combinatorial allocation of tasks to cameras). Moreover, they also involve substantial stochastic uncertainty (regarding the movement of the targets, measure ment noise and errors, etc.). The problems of interest can therefore be formulated in the framework of stochastic hybrid systems. Specifically, common surveillance tasks such as target acquisition and target tracking can naturally formulated as stochastic reachability problems, where the objective it to maximize the probability that the specific task is accomplished.

Real Time Computation & optimization for Networked Camera Surveillance

NetCam

PrinciPal investigator Prof. John Lygeros, ETHZ

Prof. Takkuen John Koo, Shenzhen inst. of advanced Technology

PrinciPal investigator Prof. Andreas Züttel, EMPA

Dr. Andreas Borgschulte, EMPAProf. Ping Chen, Dalian inst. of Chemical Physics (DiCP)Prof. yao Zhang, Dalian inst. of Chemical Physics (DiCP)

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The main objective of this Pilot Project is to develop a new technology platform of a SiC thin membrane with engineered nanopore structures for potential use in (bio)fuel cell application. The fabrication of the SiC nanopore membrane includes two key technologies: one is material preparation, and the other is the bulk micromachining process.The Peking university team prepares and characterizes SiC thin film on Si substrate, systematically investigates growth conditions and optimizes its mechanical properties, by performing PECVD or LPCVD at different temperatures and studying the effects of growth and annealing conditions on the morphology, crystal structure, roughness, young modulus, hardness and stress. The EPFL team develops process flows to pattern nanopore structures in the film and further fabricate SiC nanomembranes. They will adapt deep reactive-ion etching (DRiE) process to engineer nano channel structures in SiC thin film based on top-down lithography, or alternatively by a bottom-up approach by transferring self-assembled nanostructures of a mask into a membrane thin film. Free-standing SiC nanopore membrane can subsequently be achieved by further releasing the film from Si substrate. Together, Peking university and EPFL will functionalize the etched SiC pores with appropriate polymer or molecular monolayer to enhance proton transport through the membranes. if successful, we will further develop a microfluidic cell to demonstrate the principle of a biofuel cell by using glucose as fuel and enzyme as catalyst.The system is designed to gain advantages of high efficiency, chemical and mechanical stability, as well as scalable fabrication process

SiC nanomembranes for MEMS biofuel cell

SiC-nanomembranes

The project seeks to develop a compact optofluidic 3D imaging cytometry system for high throughput screening of micro-scale objects based on their chemical fingerprint. By properly designing the optical system and selecting two excitation laser beams, we take holographic pictures based on the emission of Coherent Anti-Stoke Raman scattering (CARS) from the objects. A 3D image of the each object can be then digitally reconstructed.

Different from conventional optical microscopy method including phase contrast and fluorescence, CARS is a technology for bio-specimen imaging with chemical contrast without labelling. As the contrast of CARS image is based on the inherent molecule vibrational characteristic, CARS provides a high resolution and sensitive method for non-invasive imaging which is particularly suitable for high throughput screening of biological samples. on the other hand, digital holographic method provides a single shot method for recording 3D images of objects, which is especially suitable for high throughput imaging screen of living cells. This project will develop an on-chip, self-reference interferometry method for recording the CARS hologram, hence simplifying the optical setup and improving reliability.

The collaboration of Prof. Psaltis’s group in EPFL with the group of Prof. Shi in Peking university benefits from the complementary expertise of the two groups. The EPFL group has extensive experience and a record of past developments in optofluidic devices. The EPFL group has strong capability in micro-optic and microfabrication. The Peking group has extensive experience in nonlinear optics and holography, especially in the areas of CARS spectroscopy and imaging. The convergence of the optical skills in nonlinear optics and microfabrication will pave the way to developing a compact and low cost nonlinear optofluidic 3D imaging cytometry for fast screening of bio-specimen. The potential impact of this work is in the areas of both health and environment monitoring. in particular, the consortium expects valuable applications in food and water safety monitoring due to the high sensitivity and throughput of this method.

optofluidic 3D chemical imaging cytometry based on inline digital coherent anti-Stoke Raman scattering holography

3DOptoChemiImage

PrinciPal investigator Prof. Jürgen Brugger, EPFL

Prof. Haixia Zhang, Peking university

PrinciPal investigator Prof. Demetri Psaltis, EPFL

Prof. Kebin Shi, Peking university

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The aim of this project is the theoretical study, design and characterization of implantable antennas dedicated to in-body telemetry. The latter is used to transmit sensor data from an implanted module to a base station located out of the body, and receive instructions (for drug delivery for instance) from the same base station. Applications for this project are far field telemetry, where sensor communications with base stations relatively far from the body are considered.

This project studies the effect of a complex dielectric environment on the antenna characteristics and elaborate new theoretical limits on what can be obtained. Classical antenna design and characterization techniques will be enhanced to consider this new environment. The results obtained will be tested by designing ultra miniature implantable antennas that will be used in the i-ironiC project.

PrinciPal investigator

Prof. Anja Skrivervik, EPFL

Prof. Juan Ramon Mosig, EPFL

Bio implantable antennas BioAnt

Wireless body sensor network (WBSN) technologies promise to offer large-scale and cost-effective solutions to the problem of increasingly prevalent cardiac and neurological diseases. outfitting patients with wearable, miniaturized and wireless sensors able to measure, pre-process and wirelessly report cardiac and neurological signals to telehealth providers would enable the required personalized, long-term and real-time remote monitoring of chronic patients.

To successfully deploy WBSNs able to perform long-term, remote and clinically relevant monitoring of chronic patients in free-living conditions, it is critical that sensor devices become vanishingly small and autonomous, while retaining their embedded intelligence and wireless capabilities. Significant research contributions remain to be made in terms of ultra-low-power embedded compression of ECG and EEG signals and ultra-low-power WBSN connectivity. This project proposes a novel and promising approach to tackle the former challenge. More specifically, it devises low-complexity, yet powerful multi-lead cardiac and neurological bioelectrical compression techniques and designs their supporting ultra-low-power sensor digital processing platform.

BioCS-NodeEnabling ultra-low-power ambulatory

monitoring of cardiac and neurological

bioelectrical signals using compressed sensing

PrinciPal investigator

Prof. Pierre Vandergheynst, EPFL

Prof. David Atienza, EPFL

EMoA

This project tackles in-house safety by communicating domestic incidents such as a person falling or unusual behavior. The use of multiple video sources provides a powerful, flexible and accurate surveillance/detection system. With this purpose, we envision a distributed smart camera system, based on low-power embedded systems-on-chip targeting image processing and network communication.

The ultimate goal pursued by this project is thus the enhancement of the existing single smart camera fall detection system, developed at iSiC/He-Arc, to cover a larger field of view and make the system more robust. This depends on a successful implementation of a mobile agent middleware on the target embedded platform. Such middleware has to be designed for distributed image processing, where two or more cameras can cooperate for a single task such as tracking a person. The main requirements of such a mobile agent system for distributed smart cameras are: lightweight, abstractions of image processing, collaborative image processing, and synchronizations.

Embedded mobile agent framework for

smart buildings

PrinciPal investigator

Prof. François Tièche, HES-So

Dr. Nuria Pazos, HES-So

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Enabler

This project addresses the power dissipation as the greatest challenge for today’s nanoelectronics, from a novel device and circuit hybrid design perspective. Tunnel FETs are steep slope switches that address critical power issues in nanoelectronics and are considered as the candidate with the highest potential for low power circuits and systems.

The Enabler project focuses on the development of a modeling and simulation environment necessary to enable to co-design of steep slope switches with advanced CMoS for novel energy efficient integrated circuits. its goal is to establish the core physical modelling and derive basic compact DC models, calibrated and validated on nanowire tunnel FETs, in order to enable the emergence of future hybrid Tunnel FET-CMoS iC design. Two state-of-the-art trends in the realization of tunnel FET architectures will be particularly followed: ultra-low power all-silicon (Si or SiGe source) device, integratable on advanced CMoS platforms, and device based on iii-V materials, also integratable into the future CMoS platforms that are expected to exploit novel super-mobility iii-V material channels for n-MoSFETs.

Enabling energy efficient tunnel

FET-CMoS co-design by compact

modeling and simulation

PrinciPal investigator

Prof. Adrian ionescu, EPFL

Dr. Heike Riel, iBM ZRL

Prof. Andreas Schenk, ETHZ

Gestational diabetes mellitus (GDM) occurs during pregnancy due to increased resistance to insulin. The current treatment approach includes a planned diet, exercises, self-blood glucose monitoring tests and frequent visits to the dietician. Fast action is crucial in case of hyperglycemia and specific symptoms to prevent any serious complication. This project proposes the deployment of a pervasive healthcare infrastructure to monitor GDM patients and inform their caretakers with historical values and alerts. To setup this infrastructure, a ubiquitous multi-agent system is deployed pervasively in the environment and accessible to users by means of smart phone devices. The data produced by wearable sensors is fed in the distributed multi-agent infrastructure. The intelligent agents deployed in the infrastructure use the data to pre-diagnose possible conditions and alert health professionals in charge of the patient. The primary goal is to break the boundaries of hospital care, allowing patients to be monitored while living their day-to-day life.

Gestational diabetes expert-based monitoring

aided by networks of distributed agent

environments

PrinciPal investigator

Prof. Michael schumacher, hEs-so

Dr. Juan Ruiz, CHuV

G-DEMANDE

optical frequency combs have revolutionized optical frequency metrology in just a few years, but a major obstacle has been the lack of integration; it has been impossible to create compact on chip comb sources. The aim of this project is to build a planar optical frequency comb generator on a chip using CMoS compatible processing. it complements the Nano-Tera projects irSens and MixSEL by targeting multi-wavelength sources not based on semiconductor based materials, but rather by nonlinear frequency conversion.

The project builds on the 2007 discovery of the principal investigator, who has demonstrated an entirely new way of generating combs, without making use of mode locked lasers. Concretely, it will develop fully integrated nanophotonic waveguides and microresonators on the same silicon chip using SiN (and Hfo2). using atomic layer deposition, dispersion will be controlled and broadband frequency combs generated. The overall objective is to create a phase coherent link from RF to optical on a chip as well as the demonstration of combs in the mid-iR by pumping >2 micron pump wavelength.

Chip-scale optical frequency combs for

near and mid-infrared

PrinciPal investigator

Prof. Tobias Kippenberg, EPFL

MicroComb

Nano-Tera.ch 99

The aim of this project is to prepare multifunctional magnetic–fluorescent nano-engineered systems, which would combine useful functions of superparamagnetic and near-infrared (NiR) to visible up-converting particles. The particles will also be conjugated with photosensitizing agents, thus allowing to perform locally-mediated photochemistry under NiR light illumination. Such properties render these constructs suitable for a range of applications, including bio-imaging, magnetic separation, contrast enhancement in magnetic resonance imaging, fluorescent labeling, targeted drug delivery and efficient deep-tissue treatment of cancers in photo-dynamic therapy (PDT).

The project focuses on synthesis and characterization of NiR-to-visible up-converting multifunctional nano-constructs based on highly efficient up-converting phosphors (Nayf4:yb3+,Er3+) and superparamagnetic iron oxides. For performing local bio-oxidations the outer shell of the constructs will be functionalized with photosensitizers of reactive oxygen species (RoS). The overall aim of the project is to explore technological routes towards obtaining efficient NiR-to-visible up-converting multifunctional nano-phosphors and bring them closer to biomedical applications.

Core-shell superparamagnetic and up-

converting nano-engineered materials for

biomedical applications

PrinciPal investigator

Dr. Andrzej Sienkiewicz, EPFL

Prof. alke fink, unifr

NanoUp

This project proposes a new approach toward the in-situ addressing of nanowires. The starting point is the FluidFM, an atomic force microscope (AFM) provided with microchanneled cantilevers for local liquid dispensing and stimulation of single living cells under physiological conditions. on the one hand, the accurate force feedback of the AFM allows for a reliable and automated approach of the cantilever tip onto both hard and soft surfaces. on the other hand, such microchanneled cantilevers may be loaded with any soluble molecule. Because of the size match between the tip aperture and the nanowire dimensions, the FluidFM is the appropriate tool to locally modify devices made of nanowires.

Two main aspects will be treated: the individual functionalization of closely packed nanowires with specific marker biomolecules; and the fabrication of interconnecting metallic wires between micropads and conducting objects such as carbon nanotubes or polymer chains, preadsorbed on an insulating surface.

Nanowire bonding: in-situ interconnecting

and addressing of individual nanowires

PrinciPal investigator

Dr. Tomaso Zambelli, ETHZ

NaWiBo

Monitoring the vital signs of preterm infants and severely ill newborns is crucial, including the arterial oxygen saturation (Spo2), measured by pulse oximetry and tissue oxygen saturation (Sto2), measured by near-infrared spectroscopy. State-of-the-art probes for spo2 are attached around the hand and foot, locations that are prone to motion artefacts due to the tendency of babies to move arms and legs, causing inaccurate measurements and false alarms. Sto2 is a novel parameter, which reflects the oxygenation of the brain, an organ which is highly sensitive to lack or excess of oxygen.

This project seeks to build a novel integrated system that is able to monitor the Spo2 more robustly and accurately, uses up less body surface of the newborn infant, monitors brain sto2, and fuses the data intelligently to achieve a higher sensitivity, specificity and reliability. To prevent motion artefacts, the novel Spo2 sensors will be positioned on the trunk.

Novel integrated wearable sensors

for multi-parameter monitoring

in critically ill newborns

PrinciPal investigator

PD Dr. Martin Wolf, uSZ

Dr. olivier Chételat, CsEM

PD Dr. Jean-Claude Fauchère, uSZ

NeoSenseRT

DNTF

EDSS

STC

100 Nano-Tera.ch

Body Area Sensor Networks (BASNs) are low cost sensor networks, very often wireless, that are designed to sense physiological parameters, such as heart rate and blood pressure, and that allow easy access to users critical and non-critical data.

This project addresses the problem of security for BASNs, in the light of the new possibilities and challenges provided by novel technological libraries. in particular it aims at providing BASNs with strong cryptographic primitives and with robustness against physical attacks, and at evaluating the effect of such design decisions on the communication protocol. The approach is to take advantage of the novel technological libraries to develop novel devices supporting standard algorithms. Furthermore, the methodology aims at considering all the design variables since the beginning of the design process, evaluating the effects that each optimization step in one direction has on the other parameters. This project represents one of the first attempts to consider security and robustness against physical attacks together with the other primary design variables.

Design of very low power robust and secure

nodes for wearable sensor networks

PrinciPal investigator

Prof. Mariagiovanna sami, usi

Prof. silvia Giordano, suPsi

Dr. Francesco Regazzoni, uSi

SecWear

The development of microfluidic technology has revolutionized biological research thanks to the fluid handling capabilities, integration and economies of scale it offers. Currently, microfluidic devices are highly specialized components that require expert knowledge for their design and fabrication. The application specificity of designs significantly increases the cost of microfluidic technology and reduces its applicability.

This project developed a new class of generally applicable microfluidic devices that can be reconfigured for different applications by means of software. These software-reconfigurable devices do not require application-specific designs leading to a subsequent reduction in cost. Conversely, the necessary programs and methods required for each application can be easily distributed along with the devices or even developed by the end-user. The devices build of the development of multilayer soft-lithography and microfluidic large-scale integration that enable the fabrication of devices featuring a high-density of active components at very low cost.

A programmable, universally applicable

microfluidic platform

PrinciPal investigator

Prof. Sebastian Maerkl, EPFL

PMD-Program

Safe and cost-effective operation of transportation structures is an issue of considerable importance. use of high-performance structures made from lightweight composite materials has intensified research in damage mechanics and damage prevention. Structural Health Monitoring (SHM) systems are useful for damage detection on structural elements under laboratory conditions: they assess structural integrity or damage accumulation under applied service loads, providing information that can be used to improve safety or optimize maintenance.

SHM of transportation structures requires integration of the monitoring system into the structure. This project develops the main components (transducers, signal transmission, data processing and analysis) to a level ready for integration into a real application. The main problems to be solved are the development of (1) sensitive transducer networks for large-scale structures that allow for localization of damage sites, (2) electronic modules for signal pre-processing, storage and wireless transmission to a central data acquisition unit, and (3) algorithms for automated signal processing, analysis and evaluation that indicate in the end whether maintenance or other actions are required. The expected benefits are numerous: even though transportation structures are at the focus of the project, the SHM system can be adapted to other types of structures.

Structure monitoring system for high

performance transportation systems

PrinciPal investigator

M.Sc. Christian Dürager, EMPA

Dr. Andreas J. Brunner, EMPA

Prof. Andreas Heinzelmann, FHo

Prof. Manfred Morari, ETHZ

SMTS

Nano-Tera.ch 101

Electronic textiles have a wide range of potential applications in wearable computing, medical monitoring, assistance to the disabled, and distributed sensor networks. The integration of electronics component within the textile yarn is the next step in the evolution of e-textiles and brings electronic-textile integration below the device-level.

While the Nano-Tera TecinTex RTD project seeks to improve on the state-of-the-art woven e-textiles by fabricating thin-film temperature and pressure sensors on plastic substrates and weaving a true e-textile with a commercial machine, the TWiGS project focuses on integrating capacitive chemical gas sensors (humidity and Volatile organic Compounds) with optimized flexible electrodes into textiles. A simple large-area textile air-filter is being built as a demonstrator. This is to be achieved by fabricating VoC, temperature sensors and humidity sensors on plastic foils, cutting the substrate into strips and weaving the sensors into a large surface textile. The integration of humidity and VoC sensors into air filters will allow air-control systems to detect air quality in the surrounding environment and take corrective action.

Textiles with integrated gas sensors

PrinciPal investigator

Dr. Danick Briand, EPFL

Dr. Giovanni Nisato, CSEM

Prof. Gerhard Tröster, ETHZ

TWIGS

As a continuation of the uLP-Logic NTF project (see above), this project explores further the potentials of sub-threshold SCL circuits as an alternative solution for implementing ultra low power digital systems. The research results obtained in the uLP-Logic project indicate that the operating current dissipation of logic cells can be reduced to levels as low as 1-10 pA, and that the power-delay product of a typical ST-SCL gate can be well below 1 fJ. This suggests that the proposed circuit topology has a very significant potential for ultra low-power applications, and opens up completely new possibilities for dynamic power scaling under strict energy constraints.

The utilization of ST-SCL circuits also offers significant advantages in terms of power dissipation, by increasing the activity rate of the circuit. Combining this technique with variable supply current, the power dissipation (and operating frequency) of critical circuit components can be scaled over a very wide range, to an extent that is completely impossible in conventional CMoS configuration. The ST-SCL circuit topology has a very wide application range covering logic, memory, mixed-signal functions and more, thus promising to develop into a complete platform for ultra-low power ubiquitous system applications.

Sub-threshold source-coupled logic (ST-SCL)

systems for ubiquitous system applications

PrinciPal investigator

Prof. yusuf Leblebici, EPFL

ULP-Systems

The demand for implementing ultra-low power digital systems in many modern applications such as mobile systems, sensor networks or implanted biomedical systems has made the design of logic circuits in sub-threshold regime a very important challenge. This project explored new methodologies for implementing ultra-low power digital integrated systems. one of the main issues in design of ultra-low power CMoS digital circuits is the leakage current due to sub-threshold conduction and gate-oxide tunneling. The tight tradeoff among different device parameters makes the design of such systems in advanced CMoS technologies a very difficult task.

To overcome these issues, a new circuit family is proposed, based on the source-coupled differential topology. using sub-threshold source-coupled logic (ST-SCL) circuits, it is possible to reduce the stand-by current of each logic cell down to a few pico-amperes, resulting in extremely low power dissipation levels that cannot be reached using conventional circuit topologies. Experimental ST-SCL circuits have been shown to operate with an equivalent energy of 600 eV per operation.

Sub-threshold source-coupled logic (ST-SCL)

circuits for ultra-low power applications

PrinciPal investigator

Prof. yusuf Leblebici, EPFL

ULP-Logic

RTD

NTF

EDSS

STC

102 Nano-Tera.ch

EducationalKitThis activity focuses on the development of an educational kit to support hands-on teaching of wearable computing and the rapid prototyping and demonstration of simple context aware wearable computing systems. This kit is composed of hardware, software and algorithmic building blocks that can be interfaced in a simple way using “plug-and-play” principles at the hardware and software level. Applications and demonstrations are programmed with a dedicated development environment tailored for wearable computing. The kit is a one-time development effort that is reusable by the community indefinitely.

leader

Dr. Daniel Roggen, ETHZ

Dr. Dennis Majoe, ETHZ

Education kit for wearable computing

D43DThis activity consists in the organization of a tutorial course on 3D integration designed to highlight the important strides that have recently been achieved in this emerging research field. it focuses on specific issues related to vertical integration and includes world-wide renowned speakers from both academia and industry in a effort to demonstrate the different approaches and objectives that each communities has with 3D systems. it is also a unique opportunity to disseminate the research results and share the experience gained within the Nano-Tera.ch CMoSAiC project.

May 26-28, 2010 http://www.d43d.com

leader

Prof. David Atienza, EPFL

Dr. Vasileios Pavlidis, EPFL

Manufacturing, design and thermal issues

in 3D integrated systems

NanoBio2010Nanobiotechnology is a new interdisciplinary discipline that is expected to shape our future in various application areas. NanoBio 2010 is the third event of a highly successful biannual conference series that started in Tokyo in 2006 followed by Seoul in 2008. This meeting gathers the leaders of this progressive field from all over the world helping scientists to get an update on the most recent achievements in the different topics of nanobiotechnology, to discuss, to network, to exchange stimulating new ideas, and to take responsibility in forming public opinion about nanobiotechnology.

August 24-27, 2010 http://www.nanobio.ethz.ch

leader

Prof. Janos Vörös, ETHZ

Prof. Markus Textor, ETHZ

The 3rd international NanoBio conference

2010

COMESDesigning advanced (most often, distributed) embedded systems interacting with the physical world, such as the ones envisioned in the Nano-Tera.ch initiative, implies dealing with extreme complexity. The overall problem of complexity management for embedded systems is addressed in this project, which consists of two 1-2 day workshops and a 5-day school revolving around a few key topics. This aims at preparing a strong basis, considering different viewpoints and presenting challenges and solutions of specific relevance to Nano-Tera.

Sept. 23, 2009 + Nov. 16-20, 2009 + Nov. 24, 2010 http://www.alari.ch/comes

leader

Prof. Mariagiovanna sami, usi

Complexity management

in embedded systems

iCANiCAN is a global contest for young university students interested in micro-nano technology, by using micro-nano devices from sponsoring companies to create new applications. The goal of this project is to set up and organize the Swiss-based contest to select the best student team to participate to the international iCAN contest that will be held during the Transducers’11 conference in June 2011, Bejing, China. Two teams from the EPFL have been selected to represent Switzerland in China.

March 15, 2011 http://www.ican-contest.ch

leader

Prof. Jürgen Brugger, EPFL

M.Sc. Philippe Fischer, FSRMProf. Christofer Hierold, ETHZ

Contest of applications in nano-micro

technology

Nano-Tera.ch 103

ISMICTThe purpose of the iSMiCT is to bring together leading researchers and experts from the medical and hospital community with those from the information and communication technology (iCT) domains in order to exchange experiences and share new ideas and promote innovation. After previous editions in Japan (2006), Finland (2007), Montreal (2009) and Taiwan (2010), the focus of iSMiCT 2011, held in Montreux, is on “medical body area networks technology and services for personalized medicine”.

March 27-30, 2011 http://www.ismict2011.org

leader

Prof. Christian Enz, CSEM

Dr. John Farserotu, CSEM

The 5th international symposium on medical

information and communication technology 2011

SPIMDimplantable Medical Devices are increasingly being used to solve a wide variety of medical and research challenges and allow an unprecedented view into the human body as well as the ability to deliver life-saving therapies. However, they introduce potential vulnerabilities to adversaries that can result in life-threatening situations as well as compromises of privacy. This 1-day workshop brings together researchers and advocates from a range of perspectives to present recent research and experiences in this domain.

April 1, 2011 http://si.epfl.ch/SPiMD

Leader

Dr. sandro Carrara, EPfL

Prof. Wayne Burleson, EPFL

Workshop on security and privacy in

implantable medical devices

MMB2011Microtechnologies in Medicine and Biology conferences are highly focused and interactive meetings that gather people who want to do biology using microtechnologies. unlike many other conferences, MMB place the biological and/or the medical questions at the centre of the problem to be solved, rather than specific technologies. The past successes of MMB conferences are certainly due to the high scientific level of the presenters – internationally renowned scientists, physicians, chemists, physicists and engineers – but also to the friendly atmosphere providing unique networking opportunities.

May 4-6, 2011 http://www.mmb2011.org

leader

Dr. olivier Guenat, CsEM

Prof. yves-Alain Peter, EPFL

The 6th international conference on

microtechnologies in medicine and biology

MicroCoolLeveraging the development of 3D integrated systems will have a profound impact in multiple aspects of our life. Besides of course the much higher computing performance of these systems, it is expected that a very significant decrease in energy consumption will be achieved, making high performance computing into a green technology for the future. The key objective of this summer school is to convene researchers from different disciplines such that the complete spectrum of the Microscale Heat Transfer domain important to interlayer cooling of 3D-iCs is brought together in one high level training exercise.

June 5-10, 2011 http://microscale.epfl.ch

leader

Prof. John Thome, EPfL

Summer school on microscale cooling of

3D integrated systems

B-AWaREWireless Body Sensor Networks (WBSNs) have tremendous potential to transform how people interact with and benefit from information technology, but their practical adoption must overcome formidable technical challenges. The objective of B-AWaRE is to organize an educational event at EPFL in the areas related to ultra-low-power electronic circuits, WBSN system-level architectures and advanced signal processing. it is a 5-day summer school introducing the challenges and opportunities for WBSNs to young researchers and PhD students world-wide interested in this fascinating and highly promising field.

June 20-24, 2011 http://b-aware.epfl.ch

leader

Dr. Martino ruggiero, EPfL

Prof. David Atienza, EPFL

Body area wireless sensor network

summer school

RTD

NTF

EDSS

STC

104 Nano-Tera.ch

PlasmonicsThe activities in this program provide in-depth education in plasmonics, the optics of specific metallic nanostructures, an extremely dynamic field of research with applications in signal processing and optical biosensing. The topics covered by the school include both fundamental principles of optics and detailed applications in information processing and optical sensing. Thanks to the contributions from renowned teachers coming from all Europe, this summer school has a very dynamic flavor.

July 18-22, 2011 http://www.nano-tera.ch/projects/210.php

leader

Prof. olivier Martin, EPfL

Summer school on plasmonics

WIMEMS-SchoolThe scope of the WiMEMS workshop in Neuchâtel is to disseminate and enhance competences on micro and nanosystems based technologies for wireless applications in the Nano-Tera domains (health, energy, environment and security). Gathering future researchers and actors in the MEMS/NEMS field is a crucial step in the dissemination of know-how as well as to encourage exchanges and networking among participants. Ph.D. students and postdoctoral fellows attending this workshop were in touch with current research trends during this school.

September 12-13, 2011 http://namis.epfl.ch

leader

Dr. Danick Briand, EPFL

Prof. Hannes Bleuler, EPFL

Doctoral school NAMiS 2011: micro- and nano-

systems based technology for wireless applications in

environment, health and security domains

QCrypt-EDQuantum cryptography aims to achieve security from fundamental physical principles, such as the quantum mechanical phenomena of entanglement and Heisenberg’s uncertainty principle. QCrypt initiates a new conference series on quantum cryptography, seeking to bring together researchers working on all aspects of the subject build a research community in Quantum Cryptography. The conference also featured tutorials on the subject and thus provide a teaching function and help recruit junior members to the field. The mission and goals of the conference tie in very closely with the QCrypt RTD project.

September 12-16, 2011 http://www.qcrypt2011.ethz.ch

leader

Prof. Matthias Christandl, ETHZ

First annual conference on quantum

cryptography

E-PrintSwiss E-print is the 1st Swiss workshop dedicated to E-Printing, a set of key enabling technologies going well beyond established paper printing. The workshop allows professionals to identify partnership in this emerging discipline spanning across several fields including tools, ink materials, surfaces, chemistry & physics, electronics and optics. The 1.5-day workshop features invited lectures of international and Swiss key contributors to the field.

December 1-2, 2011 http://www.swiss-eprint.ch

leader

Dr. Giovanni Nisato, CSEM

Dr. Danick Briand, EPFL

Prof. Jürgen Brugger, EPFL

M.Sc. Philippe Fischer, FSRM

Swiss E-Print workshop

NextGenThe design of integrated circuits strongly relies on the accuracy of the compact models available in the circuit simulators. in this perspective the BSiM group recently proposed the BSiM6 as a new compact model to eventually replace BSiM3, BSiM4 and PSP for next generation bulk CMoS processes. BSiM6 uses many of the features that were proposed by the EKV charge-based model: this workshop convenes all the BSiM and EKV researchers as well as experts from the industry to contribute and give an update on the latest status of BSiM6 and EKV.

December 15-16, 2011 http://ekv.epfl.ch/workshop

leader

Prof. Christian Enz, EPFL

Dr. Wladyslaw Grabinski, EPFL

Prof. Adrian ionescu, EPFL

Dr. Jean-Michel Sallese, EPFL

The Nano-Tera workshop on the next

generation MoSFET compact models

Nano-Tera.ch 105

EASYone of Switzerland’s leading ongoing Future Emerging Technologies Flagships is Guardian Angels for a Smarter Planet. Guardian Angels are future zero-power intelligent autonomous systems featuring some well defined human-like functions but having many other capabilities beyond human aptitudes. With Nano-Tera.ch covering energy challenges in its continuation starting in 2012, two major educational events dedicated to the advancements, challenges and opportunities of energy aware technologies and system will be organized to enable synergies between Nano-Tera.ch and Guardian Angels.

July 2011 + Feb. 2012 http://www.nano-tera.ch/projects/215.php

leader

Prof. Adrian ionescu, EPFL

Prof. Christofer Hierold, ETHZ

Educational workshops on energy efficient

autonomous systems: a collaborative framework

between Nano-Tera and Guardian Angels for a

smarter Planet

FEDAMaTThis one-week, special workshop is a unique opportunity to witness first hand the upcoming revolution in systems design. it brings together leading academic researchers with iC and CAD industry leaders in order to pinpoint the shortcomings of the current design methodologies and CAD tools, identify new problems that may lie ahead, provide a vision of the new CAD tool capabilities requirements, and crystallize everything into a new paradigm for design methodologies that fully exploits the potential of new process technologies.

January 16-20, 2012 http://si.epfl.ch/DesignTechnologies

leader

Prof. yusuf Leblebici, EPFL

Prof. Georgios Stamoulis, EPFL

2011 Nano-Tera workshop on future electronic

design automation methodologies and tools

SEE-NanoThis activity consists of an outreach program that provides educational opportunities for current and future leaders in the area of nanoelectronic devices. it focuses on providing hands-on training in material development, device preparation and system characterization in nanoelectronic device fabrication for students and industry professionals in the field of nanotechnology. The program consists of a hands-on “introduction to nanoelectronics” class for MSc students, a 1-week course for mid-career researchers in industry, a 1-day seminar for business professionals evaluating possible entry points or investment opportunities, as well as various activities for young students.

http://www.nano-tera.ch/projects/213.php

leader

Prof. Vanessa Wood, ETHZ

Swiss education and entrepreneurship in

nanoelectronics

TED-ActivitiesThe diverse background of scientists in the Nano-Tera program leads to a large demand for cross-disciplinary education among the scientists, which is being addressed by an internal workshops program, which encourages interaction within the community. There is also a need for transfer of knowledge from the research institutions to the industry: this is addressed by a large continuous education program for engineers and other professionals. For students and researchers at Swiss and foreign universities and especially for young researchers from the Nano-Tera community, a condensed summer school on specific topics was organized..

2009-2011 http://www.nano-tera.ch/projects/204.php

leader

M.Sc. Philippe Fischer, FSRM

Prof. Nicolaas de Rooij, EPFL

Training, education and dissemination

activities

Mastering-NTThe Mastering-NT educational experiment extends the present teaching plan of the Master of Science in Embedded Systems Design offered by the Faculty of informatics of uSi and organized by the ALaRi institute by means of an advanced Nano-Tera-related course structured around a number of specific, cutting-edge seminars held by experts coming from a number of Nano-Tera RTD projects. A relevant point is that the project will not be just a series of seminars but a proper integrated course.

leader

Prof. Mariagiovanna sami, usi

Exposing master students to Nano-Tera innovation

RTD

NTF

EDSS

STC

106 Nano-Tera.ch

Governing Bodies

Prof. Martine rahierPresident uniNE

Prof. Jean-Dominique Vassallirectoruniversity of Geneva

Dr. Mario El-KhouryCEoCsEM

Prof. ralph EichlerPresidentETHZ

Prof. Patrick AebischerChairman and President of EPfL

Prof. Philippe Gilletalternate to the Chair andVice-President for Academic Affairs, EPFL

Prof. antonio Loprieno PresidentuniBas

Prof. Piero MartinoliPresident usi

ThE sTEEriNG CoMMiTTEE

The Steering Committee (SC), representing the Presidents/Rectors/CEo of the partners of the Nano-Tera.ch consortium; The Steering Committee is composed of the Rectors/Presidents/Directors/CEos of the partner institutions involved in the Nano-Tera.ch consortium. The Steering Committee is responsible for all decisions/actions requiring statutory authority, as well as the overall monitoring of the program, including reporting, and the implementing evaluations/recommendations of the Scientific Advisory Board and of the SNSF Evaluation Panel.

Prof. Giovanni De MicheliChair, EPfL

Dr. alex DommannCsEM

Prof. Nicolaas de RooijEPfL

Prof. Lothar ThieleETHZ

Dr. Hugo ZbindenuniGE

Prof. Boi Faltings EPfL

Prof. Mehdi Jazayeriusi

Prof. Christofer HieroldETHZ

THE ExECuTiVE CoMMiTTEE

The Executive Committee (ExCom) acting on behalf of the Steering Committee, is the scientific executive body of Nano-Tera.ch; it consists of scientists from the partner institutions appointed by the Steering Committee and is chaired by the spokesperson of Nano-Tera.ch; it is responsible for defining and monitoring the scientific and academic strategy of the program and for providing scientific guidance.

Nano-Tera.ch 107

ThE MaNaGEMENT offiCE

The Management office (Mo), responsible for operational tasks, lead by an executive director, and involving specific staff for accounting, controlling, reporting, dissemination and web presence; the Management office is operating under the supervision of the ExCom.

THE SNSF EVALuATioN PANEL

The SNSF Evaluation Panel, a group of international experts appointed by SNSF to evaluate the RTD proposals; the selection of the RTD proposal to be funded, as well as their funding level, is decided by SNSF based on the recommendations of the Evaluation Panel.

The current members of the SNSF Evaluation Panel of Nano-Tera.ch are:

- Dr. amara amara, isEP

- Prof. Manfred Bayer, Tu Dortmund

- Dr. David Bishop, Bell Labs

- Prof. Harald Brune, SNSF

- Prof. frederica Darema, Nsf (usa)

- Dr. urs Dürig, SNSF

- Prof. Rolf Ernst, Tu Braunschweig

- Prof. Georges Gielen, Leuven university

- Prof. Chih-Ming ho, uCLa

- Dr. Patrick Hunziker, university Basel

- Dr. Karl Knop, SATW

- Prof. Paul Leiderer, SNSF Chair, uni Konstanz

- Prof. Jan Rabaey, university Berkeley

- Prof. Albert van den Berg, university Twente

- Prof. Hubert van den Bergh, SNSF

- Dr. Marco wieland, sNsf

- Prof. Hiroto yasuura, Kyushu university

THE SCiENTiFiC ADViSoRy BoARD

The Scientific Advisory Board (SAB) consists of academy and industry representatives from institutions other than the ones participating in the Nano-Tera.ch consortium; it is appointed by the Steering Committee, and provides an external evaluation of the overall performance of the program, as well as recommendations for its improvement.

The current members of the SAB of Nano-Tera.ch are:

- Dr. andrea Cuomo, sTMicro

- Prof. Satoshi Goto, Waseda university

- Prof. Enrico Macii, Politecnico di Torino

- Prof. Teresa Meng, Standford university

- Prof. Heinrich Meyr, SAB Chair, university of Aachen

(visiting Prof. EPFL)

- Prof. Khalil Najafi, university of Michigan

- Prof. Calton Pu, Georgia Tech

- Prof. Lina Sarro, Technical university Delft

- Prof. Göran Stemme, Royal institute of Technology Stockholm

Dr. Martin Rajman,Executive Director

John MaxwellWebmaster

yann Dixonfinance & Control Coordinator

Dr. Patrick MayorScientific Coordinator

Jocelyne VassallliAdministrative Assistant

108 Nano-Tera.ch

Leading house

EPFL Swiss Federal institute of Technology Lausanne

Consortium institutions

CSEM Swiss Center for Electronics and Microtechnology

EPFL Swiss Federal institute of Technology Lausanne

ETHZ Swiss Federal institute of Technology Zurich

uniBas university of Basel

uniGE university of Geneva

uniNE university of Neuchâtel

uSi university of Lugano

Other partners

ALP Agroscope Liebefeld-Posieux

CePo Pluridisciplinary oncology Center

CHuV university Hospital of Vaud

EMPA Swiss Federal Laboratories for Materials Testing and Research

FHNW university of Applied Sciences Northwestern Switzerland

FHo university of Applied Sciences of Eastern Switzerland

FoEN Federal office for the Environment

FSRM Swiss Foundation for Research in Microtechnology

GAMMA Gamma Remote Sensing

HES-So university of Applied Sciences Western Switzerland

iBM ZRL iBM Zurich Research Laboratory

icare icare institute

iDQ id Quantique

iRB institute for Research in Biomedicine

iST institute for Work and Health

PSi Paul Scherrer institute

SPZ Swiss Paraplegic Center

SuPSi university of Applied Sciences and Arts of Southern Switzerland

Symbios

uniBE university of Bern

uniFR university of Fribourg

uNiL university of Lausanne

uSZ university Hospital of Zurich

uZH university of Zurich

Chinese institutions

DiCP Dalian institute of Chemical Physics

PiCB Partner institute for Computational Biology, Shanghai institute for Biological Sciences

PKu Peking university

uSTC university of Science and Technology of China, Suzhou

SiAT Shenzhen institutes of Advanced Technology