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.

1. Nanowire Sensor
Integrateable Si Nanowire Sensor
Platform for Ion‐ and Biosensing
PI: Christian Schönenberger
Department of Physics and
Swiss Nanoscience Insitute
@ University of Basel
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More than Moore  scalable sensing chip
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2. Bio- / chemical Sensor
a device that can detect molecules in a with some specificity
how can this information
be read ?
mechanically a) mass change (QCM)
b) strain (cantilever)
optically a) labelled (DNA chip)
b) refractive index
c) Plasmonics
electrically a) impedance spectroscopy
b) CV spectroscopy
c) potentiometric (e.g. zeta potential)
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Potentiometric Sensing
IS-FET
P. Bergveld / Sensors and Actuators B 88 1–20 (2003)
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3. Ion Sensitive FET (IS-FET)
channel conductance (i.e. threshold)
depends on gate charge
e.g. heparime binding on protamie
p-channel, threshold regime
-
-
-
(source-drain current)
- SHIFT
source drain
- - -
(gate potential)
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Electronic Biochip Concept
Bergveld and others
not C. Lieber et al.
one
...
....
....
but
m any
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4. Project
fabrication technology
(PSI, Basel, EPFL)
surface
functionalization
(FHNW, ETHZ
Basel‐Pharma)
on-chip and system
microfluidics simulation integration
(ETHZ, Basel) electrical characterization (D‐BSSE, EPFL)
and biochemical validation
(all)
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NW fabrication
p-type (100) SOI
> 30 nm
SiO2 ~ 10 – 25 nm
Si 40 – 85 nm
buried SiO2 (BOX) 350 nm
Si handle wafer
300 nm
Cr mask  HSQ resist contact masks
 ion implantation 70 nm
SiO2 plasma etching in CHF3 Al contact annealing
Si wet etching in TMAH
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5. NW fabrication
accumulation inversion
(non‐implanted, Al‐contacts)
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NW fabrication
Novel fabricated
GAA (gate all around) SiNWs
SS = 62 mV/dec
Ion/Ioff = 105-106
S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL
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7. Results: Nernst limit
vs liquid gate
vs back gate
µ ¶
kT
±Vlg−shif t = ±pHB 2.3 ·α
q
µ ¶
Cdl,ox
corrected ±Vbg−shif t = ±Vlg−shif t
Cbg
O. Knopfmacher et al. Nano Lett. 10, 2268 (2010)
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Results: Noise Measurements
C. Beenakker and C. Schönenberger,
Physics Today, Vol. 56, issue 5, page 37-42 (2003)
FFT
Tarasov et al. , APL, 98, 012114, (2011)
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8. Results: Noise Measurements
threshold noise:
400 ppm of pH
Tarasov et al. , APL, 98, 012114, (2011)
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Functionalized surface
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
d) alkane with R=CH3:  0 mV/pH
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9. Biosensing
Affinity Determination of Receptor-Ligand Interaction (lectin-sugar interaction)
Human Asialoglycoprotein-Receptor (hASGP-R)
ligand + cargo and the ligand GalNAc (N-acetyl-galactosamine)
adapted from the thesis of
Claudia Riva, Uni Basel 2007
ASGP-R plays an important role
in the endocytosis in liver cells
ASGP-R is a glycoproteins
that binds to Gal terminal
GalNAc immobilized on
ASGP-R silicon nanowire
H OH
N O O
SiNW Si O O
with binding 2 AcHN
O OH
OH
site HL-1 CRD
H OH
N O O
Si O O
AcHN
O 2 OH
OH
H OH
B. Ernst et al. N O O
Si O O
AcHN
O 2 OH
OH
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Biosensing
add ASGP receptor
glycoconjugate Gal
frequency change (Hz)
R=
GluNAc (glucose)
1 GalNA (galactose)
2
3 6
5 time (min)
QCM test experiment: Change in
4 frequency for the GalNAc ligand
(yellow) and negative control having
the GluNAc ligand (grey)
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11. 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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12. Advanced Nanowire Chip and Flow Cell
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Combined metall & Si device
redish = Au on top
Si-nanowire
diameter: ~40nm
height: Au ~5nm
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13. Upscaling
quarter of 8``SOI‐wafer (supplier Soitec) for implantation:
20 x 20 mm2 chips are required
100 mm => containing four devices
(1) 20 mm
2 9 10
20 mm
100 mm
8/1 8/2
3 8 16
8/4 8/3
4 7 12 15
5 6 13 14 17
number of number of
20x20mm2 device
chip
16 x 4 devices with 48 FETs each
= 3‘072 FETs (written at once with e-beam)
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Upscaling
30

14. Upscaling
31
Upscaling & Integration
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15. 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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Readout
The nanowire drain‐source voltage is
clamped.
Differential measurement using a
reference and a sensing
nanowire.
sigma‐delta converter
compact and power‐efficient implementation.
Shepherd, L. et al., ``A novel voltage-clamped CMOS ISFET sensor Interface”, ISCAS 2007
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16. CMOS interface: first prototype chip
Contacts for
integrated gold
nanowires
Deposited by
3.4 mm
PSI in a CMOS
post‐
converters
buffers processing
Sigma‐Delta
Voltag
procedure
modulators
I to F
e
Fabricated in
0.35μm
CMOS
PAD technology
S
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4 mm
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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17. Thanks to....
Uni Basel Uni Basel
physics pharma
Christian Oren Wangyang Fu Mathias Wipf
Michel Calame Alexey Tarasov Beat Ernst Arjan Odedra
Schönenberger Knopfmacher
EPFL PSI
Mohammad Birgit Vitaliy Christian
Adrian Ionescu Sara Rigante Jens Gobrecht Kristine Bedner
Najmzadeh Päivänranta Guzenko David
ETHZ D-BSSE
Bernd Robert Andreas
Janos Vörös Paolo Livi Yihui Chen
Dielacher MacKenzie Hierlemann
FHNW Sensirion
Uwe Pieles Jolanta Kurz Matthias Sreiff
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