nanowiresensor
DESCRIPTION
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
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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 index
c) Plasmonics
electrically a) impedance spectroscopy
b) CV spectroscopy
c) 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
rren
t)
-
-
-
-- -
-
e.g. heparime binding on protamie
SHIFT
p-channel, threshold regime
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Electronic Biochip Concept
C. Lieber et al.not one ... .... .... but many
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 nm
SiO2
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
�‰operation���: enhancement��mode�‰insulator��Layer�: HfO2, tins =��5��nm,���‰poly�rSi��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
10�Pm
Si NW
sealing layer
liquid channel
SiO2 surface��leaks
Al2O3 no��leakage
HfO2 in��progress
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Results: Nernst limit
vs liquid gate
vs back gate
corrected
±Vlg−shift = ±pHB
µ2.3kT
q
¶· α
±Vbg−shift = ±Vlg−shift
µCdl,ox
Cbg
¶
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-R
GalNAc immobilized onsilicon nanowire
HN
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
uen
cy change (Hz)
time (min)
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Biosensingstrongly lectin binding glycoconjugate
R =
add ASGP receptor
NW
inactive structureChanges in the frequency of an oscillation quartz crystal upon binding of the asialoglycoprotein to the glycoconjugate
Lectin, 20 �Pg/ml
freq
uenc
y��cha
nge��
��(Hz)�
������
������
�����
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Biosensing
strongly lectin binding glycoconjugate
add ASGP receptor
inactive glycoconjugate structure
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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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Upscaling
quarter 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 m
m
Voltag
e buffers
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 technologyPAD
S
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 Dielacher
Janos 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