Nanowire Sensor Integrateable Si Nanowire Sensor Platform for Ion- and Biosensing

PI: Christian Schnenberger Department of Physics and Swiss Nanoscience Insitute @ University of Basel

More than Moore

Electronic Biochip Concept

label free, disposable (cheap) electronic chip
Lieber et al. Science 2001

molecular interface
biomolecular-

electronic interface

electronic-side

Ion Sensitive FET (IS-FET)

channel conductance (i.e. threshold) depends on gate charge p-channel, threshold regime

(source-drain current)

source

drain

(gate potential)

Ion Sensitive FET (IS-FET)

channel conductance (i.e. threshold) depends on gate charge p-channel, threshold regime

(source-drain current)

source

drain

(gate potential)

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
(source-drain current)

SHIFT

(gate potential)

Concept & Team

Analyte

Receptor

Transducer

Signal processing

Nanowire fabrication

Nanowire fabrication
p-type (100) SOI
Si SiO2

step 1.
~10nm

step 2.+3.
Weff = Wtop + 2Wwalls

80nm 145nm

Si handle wafer

wire length:6um width: 100nm-1um

step 4.+5.

step 6.+7.
metal

100nm

PMMA

step 11.to14.
SU-8

silicon silicon oxide ALD oxide resist metal epoxy

Kristine Bedner et al.
9

Nanowire fabrication
A partially double-gated fin field effect transistor (DG-FinFET) is the electronic sensing architecture.

_ _ __ _ _

operation 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 = 51016

S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL

10

Nanowire fabrication
Solid nanowire array

Particle based nanowire array

11

SOI-based NWs
AlSi contacts 48 silicon nanowires/sample top width: 100nm 1m

back gate contact

epoxy

microchannel nanowire

SU-8

wire bonds 10 mm

5m

drain
12

FinFET NWs
One die incorporates: o FinFET based sensors and metal gate transistors (single and multi wires) o Amplifying architectures based on two FinFET components AlSi
Au 25 m wire ball bonding Sensor FinFETs

SU-8

SU-8 A-B Si Fin Pt

Si Bulk

AlSi connections Epotecny conductive glue

SiO2

13

Microfluidics

Devices location in -fluidic channels

14

in the lab in operation

15

System Concept
low-noise circuitry on chip biasing and modulation technique A/D conversion nanowires can be integrated on the chip or can be interfaced via a PCB board

Micro fluidics

Si-NW chip CMOS chip

PCB

16

System Architecture

16 nanowires can be interfaced in parallel voltage across each nanowire is kept constant, and the current flowing through is measured Two different analog-to-digital converter architectures are used (12 bits resolution) Current range: 1 nA to 5 A Paolo Livi et al.
17

CMOS readout

Power consumption: 35 mW I2F resolution: 8 bits (50 pA 1 A range) 10 bits (10 nA 400 nA range) Sigma-Delta resolution: 12 bits in the range 2 A
Paolo Livi et al.
18

18

System Architecture

VDS = 200 mV

Nanowire Sensor Chip

sigma-delta modulator read-out of 4 Si-NW, 9.-10. Nov. 2011

CMOS Readout Chip

Paolo Livi et al.

19

System Architecture

Cross section: 31 nm x 15 nm Length: 380 m Patterned via e-beam and lift-off

+ 500 mV Reference Electrode Voltage
146

SU-8 microchannel for measurement in liquid

Adsorption of Cl(resistance increases) 0V - 500 mV

Resistance [kW]

145

144

Adsorption of Na+ (resistance decreases)

Average Measurement 50 100 150 200 250 300 Time [s] 350 400 450 500

143

142 0

20

Sensor parameters
o o o o o o o o o sensitivity selectivity referencing resolution signal-to-noise reproducibility stability drift response time

extensive studies addressing these parameters using Si nanowires with ALD passivation

21

Sensor parameters
(low p-doped wires in accumulation with p+-implanted and alloyed contacts) pH response & sensitivity
9.0 7.5 6.0 120mV/dec pH 3, 5, 7, 9
(S) G (S) G
22

10 10 10 10

-5

-6

-7

(S) G G (S)

reproducibility
8 width =1m NW 1 NW 2 10 10 6 120mV/dec 4 pH 7 Vbg=-6V Vsd=0.1V 0 -0.5 0.0 0.5 Vref (V) Vref (V) 1.0 1.5 10 10 10 10 2.0
-5

4.5
-8

3.0 1.5 0.0

Vbg=-6V Vsd=0.1V width =1m -0.5 0.0 0.5 1.0 1.5

-6

10 10 2.0

-9

-7

-10

GG(( S) S)

G (S) (S) G

-8

Vref V(V) (V)

ref

-9

-10

with good ALD oxides, HfO2 and Al2O3 always reach maximum sensitivity of ~ 60 mV/pH

Nernst limit and scalability

Vlg Vref
V A

drain source

Vsd

Vbg
A

max sensitivity down to the smallest nanowire with < 100 nm in width both for Al2O3 and HfO2
K. Bedner et al.
23

Sensor parameters
we have a) a transistor that maximally responds to protons (sensor) with high reproducibility and low hysteresis

24

Si-ISFET: reference
octadecyldimethylmethoxysilane (C18 alkane silane) passivation
contact angle []

120 100 80 60 40 20 0

Contact angle measurements:

3 4 5 time [days]

A. Tarasov et al. Langmuir 28, 9899 (2012)

25

Sensor parameters
we have a) a transistor that maximally responds to protons (sensor) with high reproducibility and low hysteresis b) a transistor that does not respond to protons (reference)

26

Specific ion sensor

Detection of potassium - differential signal: active and control channel Vth= (Vth,active Vth,control) = 39 mV/dec, negative Vth, due to adsorption of positively charged K+ - selective detection control experiment: no response to Na+
M. Wipf et al.
27

Specific ion sensor

Detection of sodium - differential measurement setup elimination of non-specific Cl- ion adsorptoin, drift, etc. Vth= 44 mV/dec

- selective detection control experiment: no response to K+

28

Sensor parameters
we have a) a transistor that maximally responds to protons (sensor) with high reproducibility and low hysteresis b) a transistor that does not respond to protons (reference) c) a transistor that can sense other ions selectively

29

Noise Measurements
6 5 4
G (S)

100nm 200nm 400nm 1m

3 2 1 0 -1.5 Al2O3, Vsd=0.1V -1.0 -0.5 0.0 Vgate (V) 0.5 1.0 1.5

signal

FFT
Sv (Vrms/Hz)

10 10 10 10 10 10 10 10 10 10 10

-5 -6 -7 -8 -9

time

9.26M 14.07M 28.14M 58.60M

1.16M 1.49M 3.14M 5.73M

321k

321k 498k 802k

-10 -11 -12 -13 -14 -15

Wtop=100nm, Al2O3 67mM, pH 7, Vsd=0.1V 1 10

1/f

100

A. Tarasov and K. Bedner et al. , e.g. APL, 98, 012114, (2011)

f (Hz)

30

Noise Measurements
pH 7 solution
SVG at 10 Hz (V /Hz)

100 nm 200 nm 400 nm 1 m

SVG at 10 Hz (V /Hz) normalized by W eff

pH 7 solution

100nm 200nm 400nm 1 m

10

-9

10

-9

contact regime

10

-10

SiNW regime

10

-10

10

10

10

10

10

10

RWeff (cm)

RW eff ( cm)

noise-source = trapping detrapping noise - SVG noise increases with decreasing SiNW width after normalization by SVGWeff : same noise for all the nanowire widths - sensor resolution: SVG= 110-5V/Hz1/2, which corresponds to ~100ppm of pH
31

Sensor parameters
we have a) a transistor that maximally responds to protons (sensor) with high reproducibilty and low hysteresis b) a transistor that does not respond to protons (reference) c) a transistor that can sense other ions selectively (and fast) d) resolution can reach 100ppm/sqrt(Hz) for a 1m-wide wire. Note: the resolution (signal-to-noise) is better for wider wires !!! (nano is not always better)

32

Reproducibility & Stability

Stability measurements 5.5 days
0.235 0.230

0.225

HfO2 gate oxide pH 6 buffer solution

0.220

Vth [V]
8 width =1m NW 1 NW 2 10 10 6
G (S)
-5 -6

0.215

0.210

0.205

0.200

120mV/dec 4 pH 7 Vbg=-6V Vsd=0.1V 0 -0.5 0.0 0.5 Vref (V) 1.0 1.5

10 10 10 10 2.0

-7

24

48

72

96

120

G (S)

Time (h)

-8

-9

-10

FinFET sample (EPFL) 8nm HfO2 gate ox pH6 buffer solution 4 different nanowires Max. Drift ~2mV/day differential drift ~ 0mV
33

Sensor parameters
we have a) a transistor that maximally responds to protons (sensor) with high reproducibilty and low hysteresis b) a transistor that does not respond to protons (reference) c) a transistor that can sense other ions selectively (and fast) d) resolution can reach 100ppm/sqrt(Hz) for a 1m-wide wire. Note: the resolution (signal-to-noise) is better for wider wires !!! (nano is not always better) e) reproducible and high long term stability

34

Sensor parameters
we have a) a transistor that maximally responds to protons (sensor) with high reproducibilty and low hysteresis b) a transistor that does not respond to protons (reference) c) a transistor that can sense other ions selectively (and fast) d) resolution can reach 100ppm/sqrt(Hz) for a 1m-wide wire. Note: the resolution (signal-to-noise) is better for wider wires !!! (nano is not always better) e) reproducible and high long term stability
what about biomolecules ???
Antibody

~10 nm

HO O OH OH

NHAc O O O O HN

~1 nm

Si

Small molecule

35

Targets for Biosensing

Affinity Determination of Receptor-Ligand Interactions (lectin-sugar interaction) I. Human AsialoglycoproteinReceptor (ASGP-R)
plays an important role in the endocytosis in liver cells binds to terminal GalNAc (N-acetyl-Dgalactosamine) residues GalNAc immobilized on a Si-NW CRD of ASGP-R
HO HO OH O O O O n O O O n O O O n N H Si N H Si
OH OH O O O N H Si

II. Bacterial lectin FimH

plays an important role during the invasion of uropathogenic bacteria binds to n-heptyl-mannose n-heptyl-man immobilized on a Si-NW CRD of FimH
HO HO OH OH O O O OH OH O O O N H Si N H Si HO HO

NHAc HO HO OH O

N H

Si

NHAc HO HO OH O

HO HO

NHAc

Beat Ernst et al.

36

Protein Sensing II (FimH)

2 g/mL =107 nM FimH 10 g/mL = 536 nM FimH

2 g/mL =107 nM FimH

10 g/mL = 536 nM FimH

HO HO

OH OH O O O OH

strongly lectin binding glycoconjugate ligand

inactive glycoconjugate control

buffer: 20mM HEPES, 150 mM NaCl, 1mM CaCl2, pH=7.4

Jolanta Kurz, Arjan Odedra Arjan, Florian Binder and Giulio Navarra
37

Conclusions
1. 2.
3. 4. 5. 6. 7. 8.

maximum sensitivity (Nernst limit) can be achieved (Al2O3 and HfO2) oxide surfaces (Al2O3 and HfO2) can be highly selective to protons (yielding ideal pH sensor up to buffer conc. of 10 mM) maximum sensitivity also for the narrowest nanowires charge detection limit best for the narrowest wire, but highest resolution in concentration best for wide wires
full passivation possible ideal reference electrode full sensitivity with high selectivity to other ions can be achieved (here tested K) on functionalized electrodes unclear yet (and also in the literature) whether useful for direct biomolecule sensing

38

ISFET application

ion-torrent
39

Thanks to....
Uni Basel physics EPFL
Christian Schnenberger Michel Calame Oren Mathias Wipf Wangyang Fu Alexey Tarasov Knopfmacher Ralph Stoop

PSI

Adrian Ionescu

Mohammad Najmzadeh

Sara Rigante

Jens Gobrecht Kristine Bedner

Birgit Pivnranta

Vitaliy Guzenko

Christian David

Renato Minamisawa

ETHZ

UniBas pharma
Janos Vrs Bernd Dielacher Robert MacKenzie Beat Ernst Arjan Odedra Floriian Binder Uwe Pieles Jolanta Kurz

FHNW D-BSSE

Sensirion

Andreas Hierlemann

Paolo Livi

Yihui Chen

Matthias Sreiff 40

Thanks to ...

Felix Mayer CEO Sensirion

Matthias Sreiff 41