i-IronIC, Nano-Tera Conference 2013

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    I-IRONICG. De Micheli, Q. Huang,

    L. Thoeny-Meyer, Y. Leblebici,

    C. Dehollain, F. Grassi, S. Carrara

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    What is I-Ironic?

    Implantable/wearable system for on-line

    monitoring of human metabolic conditions

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    Outline

    Motivation, objectives and overview

    The nanobiosensortechnology

    Control and readout circuit for multi-target biosensing

    Microelectronic circuits for data

    acquisition and energy harvesting

    System biocompatibility

    Conclusions and outlook

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    Objectives

    Innovative

    Nanobiosensors for

    drug and inflammation

    monitoring

    Fully implantable

    device

    Remote poweringand

    Data transmission

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    Scientific highlights

    Realization and test ofnanostructured biosensors(nanobiosensors)

    Increased sensitivity and lower detection limit

    Targeted various metabolites (drugs, glucose, lactate, glutamate, ATP)

    Genetically-engineered probes for higher robustness

    Data acqu isi t ionelectronics

    Integrated

    Low power

    Programmable

    Power and data transmission means

    Multilayer inductive coil for both power and data transmission

    Experimentation with various transmission strategies

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    Prototype: implant

    20 x 4.2 x 3 mm

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    Prototype: external patch

    FEATURES

    Remote powering through inductive link

    Short-range bidirectional

    communication

    Long-range comm. with remote devices

    ADVANTAGES

    Improved wearability

    Direct placement over implant area

    Stand alone

    Battery-powered

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    Motivation, objectives and overview

    The nanobiosensortechnology

    Control and readout circuit for multi-

    target biosensing

    Microelectronic circuits for data

    acquisition and energy harvesting

    System biocompatibility

    Conclusions and outlook

    Outline

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    The nanobiosensor concept

    BARE ELECTRODE

    CARBON NANOTUBES

    MWCNT + PROBE ENZYMES

    Boero, Carrara et al. / IEEE PRIME 2009

    Boero, Carrara et al. / IEEE ICME 2010

    De Venuto, al. et Carrara / IEEE Senors 2010

    Boero, Carrara et al. / Sensors & Actuators B 2011

    Carrara et al. / Biosensors and Bioelectronics 2011

    Boero, Carrara et al. / IEEE T on NanoBioScience 2011

    10.3 1.14 nm

    19.9 3.38 nm

    3.6

    nm

    5.2 nm

    4.9

    nm

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    Carbon nanotube benefits

    Sensor sensitivity is enhanced byCNT nanostructuration

    ~ 7.5 times more

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    Nanobiosensors sensitivity and range

    Metabolite Sensitivity(A/mM cm2)

    Range(mM)

    Detection limit(S/N = 3) (M)

    Glucose 27.7 0.5 4 73Lactate 40.1 0.5 2.5 28

    Glutamate 25.5 0.5 2 195ATP 3.42 0.5 1.4 208

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    Engineered probes for biosensors

    Protein engineering can produce better enzymesfor biosensors

    Higher affinity for analytes

    Higher stability Improved coupling efficiency

    Improved immobilization and orientation

    N-terminal domain for

    improved immobilization

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    Outline

    Motivation, objectives and overview

    The nanobiosensortechnology

    Control and readout circuit for multi-

    target biosensing

    Microelectronic circuits for data

    acquisition and energy harvesting

    System biocompatibility

    Conclusions and outlook

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    Control and Readout IC

    DAC

    DC shift& Gain

    IV. Potentiostat

    II. CV readout

    V. OCP measurement

    up/down

    counter

    I WE

    III. CA readout

    CV_out

    CA_out

    PH_out

    OP2

    OP3

    Gain

    Buf.

    Buf.

    Rm

    9bitsCLK

    (5kHz)

    Slope

    controlI. Triangular waveform generator

    OP1

    I WE

    Switch PH

    WE1

    WE2

    WE3

    WE4

    WE5

    CE

    RE

    MUX

    IrOxE

    Mu

    lti-targetbiosensor

    Electronic interface

    Q S

    nQ

    R

    Iref

    C

    1.35V

    0.45V

    1.55V

    0.9V

    1.8V

    VC

    VC

    Adder

    Current mirror

    Current to frequency

    converter

    Layout of the fabricated IC(0.18um technology)

    Low power, to be remotelypowered

    Covering a wide range ofbiosensors with differentcharacteristics

    Intelligent, to ease thehost side implementation

    High accuracy

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    IC Measurement Results

    Measurement setup

    Timing schedule for multi-target detection and calibration

    Lactate measurementCA and CV measurement

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    Architecture of the Frontend Electronics

    14 bit ADC

    DAC sharing

    Sensor Conditioning

    2 sensing sites for pH

    and temperature

    Configurable multi-

    target platform

    (7 sensing sites)

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    Outline

    Motivation, objectives and overview

    The nanobiosensortechnology

    Control and readout circuit for multi-

    target biosensing

    Microelectronic circuits for data

    acquisition and energy harvesting

    System biocompatibility

    Conclusions and outlook

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    Inductive Link

    Wireless power transfer through inductive link

    Bidirectional data communication

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    IronIC PatchPower Transmission

    Battery Life

    Up to 15 mW transmitted within 6 mm in air

    Downlink communication up to 100 kbps

    Bluetooth communication (Class-2)

    Uplink communication up to 66.6 kbps

    Stand-by mode: 10 hours

    Power mode: 1.5 hours

    Up to 1.17 mW transmitted within 17 mmbeef sirloin

    Data Transmission

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    Power & Data Transmission

    Downlink Bitstream 100 kbps Uplink Bitstream 66.6 kbps

    Power

    Data

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    Multi-layer Receiving Inductors

    Higher link efficiency (up to 35% higher)

    Higher voltage gain (up to one order of

    magnitude higher)

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    Micro-fabricated Spiral Inductors

    Trace thickness: 60 m

    Inductor size: 14.88 x 2 mm

    Inductance value: 0.46 H

    Received power: up to 8.7 mW (6 mm)

    Overall efficiency: 3.54% (6 mm)

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    Power and Data Integrated Module

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    Alternative @ 2.45 GHz

    TX Antenna Design at 2.45 GHz

    Microstrip Patch Antenna

    Directive far-field radiation

    50 input impedance

    6.5 dB Gain

    6 cm

    8 cm

    Antenna

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    Outline

    Motivation, objectives and overview

    The nanobiosensortechnology

    Control and readout circuit for multi-

    target biosensing

    Microelectronic circuits for data

    acquisition and energy harvesting

    System biocompatibility

    Conclusions and outlook

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    Challanges

    Prevent Cu leaking (coil)

    Prevent CNT diffusion (sensors)

    Prevent circuit corrosion

    Prevent sensors biofouling

    Investigations:

    Cytotoxicity tests

    In-vivo tests

    Solutions:

    Parylene C inner coating

    USP class 6Silicone external coating

    CNT entrapement in chitosan + outer

    membrane

    Biocompatibility research

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    I n vivoinflammation

    Subcutaneous implant in mice

    No significant inflammation after30 days

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    Outline

    Motivation, objectives and overview

    The nanobiosensortechnology

    Control and readout circuit for multi-

    target biosensing

    Microelectronic circuits for data

    acquisition and energy harvesting

    System biocompatibility

    Conclusions and outlook

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    Conclusions

    Continuous care of chronic patients is possiblethrough specialized bio-electronics

    Current FDA approved devices are mainly

    For glucose monitoring

    Wearable devices

    Electronic implants represent the near future

    technology and can be more patient-friendly

    Challenges include the plurality of technologies as

    well as the interaction with the human body

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    Thank you

    Andrea Cavallini Sara Ghoreishizadeh Seyedeh

    Irene Taurino

    Jacopo Olivo

    Kazanc Onur

    Tanja Rezzonico

    Michele Proietti

    Renate Reiss Michael Richter

    Michael Fairhead

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    Thank you