NanowireSensor (Nano-Tera)
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1 PI: Christian Schönenberger Department of Physics and Swiss Nanoscience Insitute @ University of Basel Nanowire Sensor Integrateable Si Nanowire Sensor Platform for Ion‐ and Biosensing
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There 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.
Transcript of NanowireSensor (Nano-Tera)
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PI: Christian SchönenbergerDepartment of Physics andSwiss Nanoscience Insitute @ University of Basel
Nanowire SensorIntegrateable Si Nanowire SensorPlatform for Ion‐ and Biosensing
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More than Moore scalable sensing chip
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Bio- / chemical Sensor
mechanically a) mass change (QCM)b) strain (cantilever)
optically a) labelled (DNA chip)b) refractive indexc) Plasmonics
electrically a) impedance spectroscopyb) CV spectroscopyc) potentiometric (e.g. zeta potential)
how can this information be read ?
a device that can detect molecules in a with some specificity
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Potentiometric Sensing
P. Bergveld / Sensors and Actuators B 88 1–20 (2003)
IS-FET
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Ion Sensitive FET (IS-FET)
source drain
channel conductance (i.e. threshold) depends on gate charge
(gate potential)
(sou
rce-
drai
n cu
rrent
)
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-- -
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e.g. heparime binding on protamie
SHIFT
p-channel, threshold regime
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Electronic Biochip Concept
C. Lieber et al.
Bergveld and others
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Projectfabrication technology(PSI, Basel, EPFL)
microfluidics(ETHZ, Basel)
simulationelectrical characterizationand biochemical validation
(all)
on-chip and systemintegration
(D‐BSSE, EPFL)
surface functionalization
(FHNW, ETHZBasel‐Pharma)
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NW fabrication
Al contact annealing
Si wet etching in TMAH
Cr mask contact masks
SiO2 plasma etching in CHF3
HSQ resist
ion implantation
Si handle wafer
> 30 nmSiO2
buried SiO2 (BOX) 350 nm
Si~ 10 – 25 nm
40 – 85 nm
p-type (100) SOI
300 nm
70 nm
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NW fabrication
accumulation inversion(non‐implanted, Al‐contacts)
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NW fabricationNovel fabricatedGAA (gate all around) SiNWs
SS = 62 mV/decIon/Ioff = 105-106
S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL
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NW fabrication
opera on → enhancement mode insulator Layer → HfO2, tins = 5 nm, poly‐Si Gates → wg = 25 nm, hg = 50 nm fin Body → hSi = 100 nm, wSi = 50nm
doping → Na = 5×1016
A partially double-gated fin field effect transistor (DG-FinFET) is the electronic sensing architecture.
S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL
_ __ ____
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Isolation
Si NW
sealing layer
liquid channel
SiO2 surface leaks
Al2O3 no leakage
HfO2 in progress
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Results (pH sensing)
Vth
back-gate
liqui
d-ga
te
O. Knopfmacher et al. Nano Lett. 10, 2268 (2010)
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Result: Modelling
∆G ≈ 40 nS
∆Vth ≈ 400 mV
O. Knopfmacher, A. Tarasov, W. Fu, M. Wipf, B. Niesen, M. Calame, C. Schönenberger, Nano Letters 10, 2268 (2010)
∆Vth = 300 mV
model by P. Livi et al. D-BSSE
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Results: Nernst limit
vs liquid gate
vs back gate
corrected
±Vl g¡ sh i f t = ±pHB
µ2:3
kTq
¶¢®
±Vbg¡ shi f t = ±Vl g¡ sh i f t
µCdl ;oxCbg
¶
O. Knopfmacher et al. Nano Lett. 10, 2268 (2010)
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Results: Noise Measurements
FFT
C. Beenakker and C. Schönenberger, Physics Today, Vol. 56, issue 5, page 37-42 (2003)
Tarasov et al. , APL, 98, 012114, (2011)
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Results: Noise Measurements
threshold noise:
Tarasov et al. , APL, 98, 012114, (2011)
400 ppm of pH
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R1=NH2, Cl, CH3
bare alumina: 45‐55 mV/pH
a) APTES: 26 mV/pH
b) CPTO+APTES: 17 mV/pH
c) after UV ozone: 32 mV/pH
Functionalized surface
d) alkane with R=CH3: 0 mV/pH
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BiosensingAffinity Determination of Receptor-Ligand Interaction (lectin-sugar interaction)
ligand + cargo
ASGP-RGalNAc immobilized on
silicon nanowireHN
O
HN
O
HN
O
O
O
O
O
O
O
O
O
O O
O
O
OH
OH
OH
OH
OH
OH
OH
OH
OHAcHN
AcHN
AcHN
2
2
2
SiNW Si
Si
Si
with binding site HL-1 CRD
B. Ernst et al.
Human Asialoglycoprotein-Receptor (hASGP-R)and the ligand GalNAc (N-acetyl-galactosamine)
ASGP-R is a glycoproteins that binds to Gal terminal
ASGP-R plays an important role in the endocytosis in liver cells
adapted from the thesis of Claudia Riva, Uni Basel 2007
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Biosensingglycoconjugate Gal
1
2
3
4
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R =GluNAc (glucose)
GalNA (galactose)
QCM test experiment: Change in frequency for the GalNAc ligand (yellow) and negative control having the GluNAc ligand (grey)
add ASGP receptor
freq
uency change (Hz
)
time (min)
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Biosensingstrongly lectin binding glycoconjugate
R =
add ASGP receptor
NW
inactive structure Changes in the frequency of anoscillation quartz crystal uponbinding of the asialoglycoprotein tothe glycoconjugate
Lectin, 20 g/ml
freq
uency change (Hz
)
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Biosensing
strongly lectin binding glycoconjugate
add ASGP receptor
inactive glycoconjugate structure
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Metallic Nanowires
Solid nanowire array
Particle based nanowire array
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Metallic Nanowires
Cl-Na+
V+V-V0
150mM NaCl
MacKenzie R., Dielacher B. et al., submitted 2010
Combined optical and electrical measurements in response to an applied solution gating voltage of ±500 mV in 1 mM NaCl.
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Advanced Nanowire Chip and Flow Cell• 4 electrodes per nanowire region• Integrated platinum counter electrodes• Integrated silver reference electrodes• SU-8 for isolation• Openings to each nanowire region channel
CE / Ag‐ref
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Advanced Nanowire Chip and Flow Cell
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Advanced Nanowire Chip and Flow Cell
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Combined metall & Si device
redish = Au on top
diameter: ~40nmheight: Au ~5nm
Si-nanowire
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Upscalingquarter of 8``SOI‐wafer (supplier Soitec)
5 6 13 14 17
151274
3 8 16
1092
(1)
100
mm
100 mm
8/1 8/2
8/38/4
20 mm
20 m
m
for implantation:20 x 20 mm2 chips are required=> containing four devices
number of 20x20mm2
chip
number of device
16 x 4 devices with 48 FETs each= 3‘072 FETs (written at once with e-beam)
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Upscaling
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Upscaling
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Upscaling & Integration
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Integration
• 16 nanowires can be interfaced in parallel• Voltage across each nanowire is kept constant, and the current flowing through is measured• The measured current is then digitized• Two different analog‐to‐digital converter architectures are used (12 bits resolution)• Current range: 1 nA to 5 μA
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ReadoutThe nanowire drain‐source voltage is clamped.
Differential measurement using a reference and a sensing nanowire.
compact and power‐efficient implementation.
Shepherd, L. et al., ``A novel voltage-clamped CMOS ISFET sensor Interface”, ISCAS 2007
sigma‐delta converter
354 mm
3.4 mm
Volta
gebu
ffers
I to F
converters
Sigma‐Deltamodulators
Contacts for integrated gold nanowires
Deposited by PSI in a CMOS post‐processing
procedure
Fabricated in 0.35μm CMOS technology
PADS
CMOS interface: first prototype chip
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Summary demonstrated reproducible and hysteresis‐free field‐effect behavior in NW‐FETs
demonstrated leakage‐free liquid‐gate operation
demonstrated pH sensing with nanowires
surface functionalization for (a) passivated nanowires (b) glycoprotein‐binding nanowires
Signal and signal‐to‐noise: noise measurements and modelling of sensitivity
systematic evaluation of physical parameters, e.g. width, length, doping, ion concentration, length of molecules etc. onoing
system concepts
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Thanks to....
Michel Calame
Uni Baselphysics
Oren Knopfmacher
Wangyang FuAlexey Tarasov
Christian Schönenberger Beat Ernst Arjan Odedra
EPFL
Adrian Ionescu Sara Rigante Kristine Bedner
Bernd DielacherJanos Vörös
Jolanta KurzUwe Pieles
Andreas Hierlemann Paolo Livi
Mohammad Najmzadeh
Robert MacKenzie Yihui Chen
BirgitPäivänranta
VitaliyGuzenko
ChristianDavid
ETHZ
Uni Baselpharma
Jens Gobrecht
PSI
D-BSSE
FHNW
Matthias Sreiff
Sensirion
Mathias Wipf
