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
2
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
how can this information
be read ?
a device that can detect molecules in a with some specificity
3
Ion Sensitive FET (IS-FET)
source drain
channel conductance (i.e. threshold)
depends on gate charge
(gate potential)
(
s
o
u
r
c
e
-
d
r
a
i
n

c
u
r
r
e
n
t
)

-
-
-
- - -
-
e.g. heparime binding on protamie
SHIFT
p-channel, threshold regime
4
Concept & Team
Analyte
Receptor
Transducer
Signal processing
5
Nanowire fabrication
6
Nanowire fabrication
PMMA
80nm
145nm
~10nm
p-type (100) SOI
SiO
2
Si handle wafer

Si

step 1.
step 4.+5. step 6.+7.
step 11.to14.
metal

SU-8
step 2.+3.
wire length:6um
width: 100nm-1um
silicon
silicon oxide
resist
metal
ALD oxide
epoxy
100nm
W
eff
= W
top
+ 2W
walls
Kristine Bedner et al.
70 nm 300 nm
7
Nanowire fabrication
 operation → enhancement mode
 insulator Layer → HfO
2
, t
ins
= 5 nm,
 poly-Si Gates → w
g
= 25 nm, h
g
= 50 nm
 fin Body → h
Si
= 100 nm, w
Si
= 50nm
 doping → N
a
= 5×10
16

A partially double-gated fin field effect transistor (DG-FinFET) is the
electronic sensing architecture.
S.Rigante, M.Najmzadeh and A. M. Ionescu, EPFL
_

_

_

_

_
_

_

8
Nanowire fabrication
Solid nanowire array
Particle based nanowire array
9
SOI-NW (working horse)
PMMA
80nm
145nm
~10nm
p-type (100) SOI
SiO
2
Si handle wafer

Si

step 1.
step 4.+5. step 6.+7.
step 11.to14.
metal

SU-8
step 2.+3.
wire length:6um
width: 100nm-1um
silicon
silicon oxide
resist
metal
ALD oxide
epoxy
100nm
W
eff
= W
top
+ 2W
walls
Kristine Bedner et al.
70 nm 300 nm
10
SOI-NW (working horse)
(non-implanted, Al-contacts)
(p+-implanted and alloyed contacts)
-0.5 0.0 0.5 1.0 1.5 2.0
0
2
4
6
8
V
sd
=0.1V

NW 1
NW 2
G

(
µ
S
)
V
ref
(V)
V
bg
=-6V
pH 7
10
-10
10
-9
10
-8
10
-7
10
-6
10
-5
width =1µm

G

(
S
)
120mV/dec
-0.5 0.0 0.5 1.0 1.5 2.0
0.0
1.5
3.0
4.5
6.0
7.5
9.0
120mV/dec
V
sd
=0.1V
G

(
µ
S
)
V
ref
(V)
width =1µm
pH 3, 5, 7, 9
V
bg
=-6V
10
-10
10
-9
10
-8
10
-7
10
-6
10
-5
G

(
S
)
back-gate
G

(
µ
S
)

G

(
µ
S
)

G

(
S
)

G

(
S
)

V
ref
(V)

V
ref
(V)

11
Ion-sensitive FET (basics)
 sensitivity
 selectivity (what can be detected in the first place and what not)
 detection limit
 signal-to-noise (origin of noise)
 scalability
 stability and reproducibility
in the following examples:
the ionic solution is in direct contact with a thin oxide layer (SiO
2
, Al
2
O
3
, HfO
2
) capping the
conducting channel of the transistor.
The OH-terminals are then the main ion-active functional groups
12
IS FET for pH sensing
taken from an application note
P. Bergveld / Sensors and Actuators B 88 1–20 (2003)
Honeywell: Durafet III
Endress+Hauser :CPS441 and CPS441D
pH sensors
13
pH sensing on oxide surface
site binding (SB) model for SiO
2
surface
(iii)
surface charge density o
S

(ii) b
SiOH
H SiOH
K
a
S
=
·
+
+
2
v
v
(i)
a
SiOH
H SiO
K
a
S
=
·
+ ÷
v
v
P. Bergveld / Sensors and Actuators B 88 1–20 (2003)
P. Bergveld, IEEE Sensor Conference Toronto (2003)
(i-iii) can be used to express
surface charge o
0
as a function
of

+
S
H
a
|
|
.
|

\
|
+ +
÷
=
+ +
+
b a b H H
b a H
S S
K K K a a
K K a
qN
S S
S
2
2
o
14
pH sensing on oxide surface
P. Bergveld / Sensors and Actuators B 88 1–20 (2003)
P. Bergveld, IEEE Sensor Conference Toronto (2003)
convert surface ion to
bulk ion concentration
|
.
|

\
|
+
÷ =
+ +
kT
e
a a
S
H H
B S
exp
def. of pH ) log(
+
÷ =
B
H
B
a pH
S
+ surface potential
Debye length
if C
dl
is “large”, then
S dl S
C + =
'
o
15
pH sensing on oxide surface
t
h
r
e
s
h
o
l
d

s
h
i
f
t

C
gat e¡ oxi de
¿ C
dl
¿ C
S
C
gat e¡ oxi de
¿ C
dl
¿ C
s
a = b C
gat e¡ oxi de
¿ C
dl
¿ C
s
A= B
maximum sensitivity given by
Nernst limit:
2.3 kT/e = 59.5 mV/pH
O. Knopfmacher et al. Nano Lett. 10, 2268 (2010)
P. Bergveld / Sensors and Actuators B 88 1–20 (2003)
P. Bergveld, IEEE Sensor Conference Toronto (2003)
C
gate-oxide
<< C
dl
<< C
S
C
dl
= double-layer capacitance
C
s
= surface-buffer capacitance
C
s
is pro. to number of OH-surface sites
16
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)


-0.5 0.0 0.5 1.0 1.5 2.0
0.0
1.5
3.0
4.5
6.0
7.5
9.0
120mV/dec
V
sd
=0.1V
G

(
µ
S
)
V
ref
(V)
width =1µm
pH 3, 5, 7, 9
V
bg
=-6V
10
-10
10
-9
10
-8
10
-7
10
-6
10
-5
G

(
S
)
17
pH-sensing / other ions?
the Al
2
O
3
surface is sensitive to
the proton concentration but
not to other ions (at least for
not too large c).

Hence, it provides an ideal pH-
sensor and max. sensitivity can
be reached (same seems to hold
true for HfO
2
)
O. Knopfmacher et al. ChemPhysChem 2011, DOI: 10.1002/cphc.201100918
18
pH-sensing / other ions?
O. Knopfmacher et al. ChemPhysChem 2011, DOI: 10.1002/cphc.201100918
19
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)
2. oxide surfaces (Al
2
O
3
and HfO
2
) can be highly selective to protons
(yielding ideal pH electrode up to a buffer conc. of 1-10 mM)


20
Nernst limit and scalability
21
upscaling
NW


SiO
2
mask
~ 180nm
Si
Si
Si
Si
K. Bedner et al.
22
upscaling
NW
K. Bedner et al.
48 silicon nanowires/sample
top width: 100nm – 1µm
DRAIN
3 SOURCE
CONTACTS
5µm
D
S
SU-8
microchannel
HfO
2
, Al
2
O
3
85nm

W
top
silicon
SiO
2
23
upscaling
quarter of 8``SOI-wafer (supplier Soitec)
5 6 13 14 17
15 12 7 4
3
8 16
10 9 2
(1)
1
0
0

m
m

100 mm
8/1 8/2
8/3 8/4
20 mm
2
0

m
m

for implantation:
20 x 20 mm
2
chips are required
=> containing four devices
number of
20x20mm
2

chip
number of
device
16 x 4 devices with 48 FETs each
= 3072 FETs (written at once with e-beam)
K. Bedner et al.
24
upscaling
25
upscaling
26
upscaling
27
Nernst limit and scalability
V
bg
V
ref
V
lg
A
V
drain
source
V
sd
A
max sensitivity down to the smallest
nanowire with < 100 nm in width both
for Al
2
O
3
and HfO
2
K. Bedner et al.
28
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)
2. oxide surfaces (Al
2
O
3
and HfO
2
) can be highly selective to protons
(yielding ideal pH sensor up to buffer conc. of 1-10 mM)
3. maximum sensitivity also for the narrowest nanowires

29
Detection limit / resolution
30
Noise Measurements
FFT
Tarasov et al. , APL, 98, 012114, (2011)
S
v
· V
2
1 µm wide wires with Al
2
O
3
31
Noise Measurements
threshold noise:
400 ppm of pH
1 µm wide wires with Al
2
O
3
Tarasov et al. , APL, 98, 012114, (2011)
contact limited (extrinsic noise)
wire limited (intrinsic noise limit 400 ppm)
32
Noise Measurements
K. Bedner et al.
different wire width & HfO
2
1 10 100
1E-12
1E-11
1E-10
1E-9
1E-8
1E-7
3.9MO
3.9MO
9.2MO
HfO
2


S
V

(
V
2 r
m
s
/
H
z
)
f (Hz)
15.4MO
25.8MO
39.6MO
90.7MO
V
bg
=-4V
V
ds
=0.09V
1/f
W = 100nm
0.1 1 10 100 1000 10000
1E-10
1E-9
1E-8
1E-7
p>1
HfO
2
V
bg
= -3V
V
bg
=-4V(100nm)
V
bg
=-2V(400nm)
V
bg
=0V(1µm)


W
(top)
=100nm
W
(top)
=200nm
W
(top)
=300nm
W
(top)
=400nm
W
(top)
=500nm
W
(top)
=1µm
V
ref
=-1.3V
S
V
/
V
2 d
s

(
1
0
H
z
)

(
1
/
H
z
)
R (MO)
p=1
V
sd
=0.09V
set-up wire contact
oV
th
~2·10
-4
V/Hz
0.5
(@ 10Hz)

33
Detection limit / resolution
different wire width Al
2
O
3
and HfO
2
oV
th
~1-4·10
-4
V/Hz
0.5
(@ 10Hz)

threshold noise:
0.1 1 10 100
1E-5
1E-4
V
sd
=0.09V


W
(top)
=100nm
W
(top)
=400nm
W
(top)
=1µm
a
v
e
r
a
g
e
d

A
V
t
h

(
V
)

b
y

W
e
f
f

a
t

1
0
H
z

(
V
/
H
z
1
/
2
)
R (MO)
 NW regime contact regimes 
can reach 200 ppm of pH compares
to one electron per wire (for the
narrowest ones)
K. Bedner et al.
170 ppm
600 ppm
detection limit
~ 200 ppm of pH (1 Hz BW at 10Hz)
better for wider wires !

34
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)
2. oxide surfaces (Al
2
O
3
and HfO
2
) can be highly selective to protons
(yielding ideal pH sensor up to buffer conc. of 1-10 mM)
3. maximum sensitivity also for the narrowest nanowires
4. charge detection limit best for the narrowest wire, but
5. highest resolution in concentration best for wide wires

35
Specificity / selectivity
OH OH OH OH
is it possible at all to suppress the high
selectivity and responsivity of oxide
surfaces to protons (pH) ?
36
Passivation (against pH)
-1 0 1 2 3 4 5 6 7 8
-10
0
10
20
30
40
50
60
70

p
H

s
e
n
s
i
t
i
v
i
t
y

[
m
V
/
p
H
]
passivation time [days]
0
20
40
60
80
100
120
CA measurements:
SiO2
SiO2
Al2O3
c
o
n
t
a
c
t

a
n
g
l
e

[
°
]

nanowire
meas.
octadecyldimethylmethoxysilane(C18 alkane silane)
p
H

s
e
n
s
i
t
i
v
i
t
y

[
m
V
/
p
H
]

c
o
n
t
a
c
t

a
n
g
l
e

-0.1
0.0
0.1
2 4 6 8 10 12
after 24 h
after 6h
pH
B
+
0
[
m
V
]
pH in bulk
s
u
r
f
a
c
e

p
o
t
e
n
t
i
a
l

dependence
is getting exceedingy
nonlinear
A. Tarasov et al.
37
Passivation
theory
A. Tarasov et al.
long time (1 hour) detection limit
< 1 surface site / (10nm)
2
(includes drift)
experiment
38
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)
2. oxide surfaces (Al
2
O
3
and HfO
2
) can be highly selective to protons
(yielding ideal pH sensor up to buffer conc. of 1-10 mM)
3. maximum sensitivity also for the narrowest nanowires
4. charge detection limit best for the narrowest wire, but
5. highest resolution in concentration best for wide wires
6. full passivation possible  “ideal” reference electrode


39
Towards a ChemFET
 we can sense electrostatic potential (after passivation)
 we can sense the chemical potential of protons (pH sensing)
 can we sense also K or other ions ?
KCl
A. Tarasov et al.
40
ChemFET
• PVC membrane cocktail dissolved in THF
• valinomycin potassium ionophore
• drop functionalization (~0.2µl)
PVC membranes with ionophore
Valinomycin: K
+
ionophore
M. Wipf et al.
41
ChemFET
All the wires show the same pH sensitivity, indicating that the PVC membrane is
fully permeable to the liquid and all (most) OH groups remain active
5 6 7 8 9
-1.2
-1.1
-1.0


without PVC membrane
V
t
h

[
V
]
pH
~50 mV/pH
with PVC membrane
M. Wipf et al.
42
ChemFET
Arrays without PVC membrane show regular behavior with increasing salt (black)
PVC+ ionophore coated arrays show negative shift in V
th
indicating adsorption of
positive charges (red)
 Differential measurement (red-black) results in a KCl sensitivity of ~-40mV/dec
1E-3 0.01 0.1 1
-1.40
-1.35
-1.30
-1.25
without K
+
ionophore


V
t
h

[
V
]
[KCl]
with K
+
ionophore
1E-3 0.01 0.1 1
-0.15
-0.10
-0.05
0.00


A
V
t
h
[
V
]
[KCl]
-42 3 mV/dec
differential measurement
M. Wipf et al.
43
ChemFET
All wires show the same response to increasing MgCl
2
concentration
PVC + ionophore only adsorbs K+

 Differential measurement (red-black) results in a MgCl
2
sensitivity of ~ 0mV/dec
differential measurement
1E-3 0.01 0.1 1
0.00
0.05
0.10
0.15


A
V
t
h
[
V
]
[MgCl
2
]
~0 mV/pH
1E-3 0.01 0.1 1
-1.15
-1.10
-1.05
-1.00
-0.95
without K+ ionophore


V
t
h

[
V
]
[MgCl
2
]
with K+ ionophore
M. Wipf et al.
44
ChemFET
Covalently bound ionophore; a K+ trap was used here (18-Crown-6)
1E-3 0.01 0.1 1
-0.1
0.0
0.1
0.2
0.3
without K
+
ionophore, in KCl
with K
+
ionophore, in NaCl


V
t
h
[
V
]
c[mol/l]
with K
+
ionophore, in KCl
R. Stoop et al. J. Kurz et al.
45
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)
2. oxide surfaces (Al
2
O
3
and HfO
2
) can be highly selective to protons
(yielding ideal pH sensor up to buffer conc. of 10 mM)
3. maximum sensitivity also for the narrowest nanowires
4. charge detection limit best for the narrowest wire, but
5. highest resolution in concentration best for wide wires
6. full passivation possible  “ideal” reference electrode
7. full sensitivity with high selectivity to other ions can be achieved (here
tested K) on functionalized electrodes


46
Targets for Biosensing
Affinity Determination of Receptor-Ligand Interactions (lectin-sugar interaction)
GalNAc immobilized on a Si-NW
CRD of ASGP-R
I. Human Asialoglycoprotein-
Receptor (ASGP-R)

• plays an important role in the endocytosis
in liver cells
• binds to terminal GalNAc (N-acetyl-D-
galactosamine) residues
CRD of FimH
n-heptyl-man immobilized on a Si-NW
II. Bacterial lectin FimH


• plays an important role during the
invasion
of uropathogenic bacteria
• binds to n-heptyl-mannose

O
HO
NHAc
O
O
n
OH
HO
N
H
O
Si
O
HO
NHAc
O
O
n
OH
HO
N
H
O
Si
O
HO
NHAc
O
O
n
OH
HO
N
H
O
Si
Si
O
HO
HO
OH
O
OH
N
H
O
Si
O
HO
HO
OH
O
OH
N
H
O
Si
O
HO
HO
OH
O
OH
N
H
O
K
D
~ 70 µM K
D
~ 50 nM
Beat Ernst et al.
47
Ligand Immobilization (I)
1
2
3
4
5
6
R =
R =
GlcNAc (control)
GalNAc (ligand)
O
HO
NHAc
O
O
OH
HO
n
O
HO
NHAc
O
O
OH
HO
O
HO
NHAc
O
O
n
OH
HO
N
H
O
Si
O
HO
NHAc
O
O
n
OH
HO
N
H
O
Si
O
HO
NHAc
O
O
n
OH
HO
N
H
O
Si
Jolanta Kurz et al.
ASGP-R
48
Protein Sensing I (ASGP-R)
f
r
e
q
u
e
n
c
y

c
h
a
n
g
e


(
H
z
)










time (min)
buffer
ASGP-R
Jolanta Kurz and Arjan Odedra et al.
O
HO
NHAc
O
O
OH
HO
n
O
HO
NHAc
O
O
n
OH
HO
QCM
50
Ligand Immobilization (II)
1
2
3
4
5
6
Jolanta Kurz et al.
R =
R =
control
n-heptyl-man (ligand)
O
HO
HO
OH
O
OH
HO
Si
O
HO
HO
OH
O
OH
N
H
O
Si
O
HO
HO
OH
O
OH
N
H
O
Si
O
HO
HO
OH
O
OH
N
H
O
FimH
51
Protein Sensing II (FimH)
buffer
f
r
e
q
u
e
n
c
y

c
h
a
n
g
e


(
H
z
)










time (min)
FimH
Jolanta Kurz and Arjan Odedra et al.
HO
OH
O
O
HO
HO
OH
O
OH
OH
O
QCM
52
Protein Sensing II (FimH)
strongly lectin binding glycoconjugate ligand inactive glycoconjugate control
UniBas2-FHNW-ETHZ-UniBas1-PSI
buffer: 20mM HEPES, 150 mM NaCl, 1mM CaCl2, pH=7.4
2 ¦g/mL =107 nM FimH 10 ¦g/mL = 536 nM FimH

O
HO
HO
OH
O
OH
OH
O
2 ¦g/mL =107 nM FimH 10 ¦g/mL = 536 nM FimH

Jolanta Kurz and Arjan Odedra et al.
53
Conclusions
1. maximum sensitivity (Nernst limit) can be achieved (Al
2
O
3
and HfO
2
)
2. oxide surfaces (Al
2
O
3
and HfO
2
) can be highly selective to protons
(yielding ideal pH sensor up to buffer conc. of 10 mM)
3. maximum sensitivity also for the narrowest nanowires
4. charge detection limit best for the narrowest wire, but
5. highest resolution in concentration best for wide wires
6. full passivation possible  “ideal” reference electrode
7. full sensitivity with high selectivity to other ions can be achieved (here
tested K) on functionalized electrodes
8. first signals from protein sensing


54
upscaling
55
System Concept
PCB Si-NW chip CMOS chip
Micro fluidics
• 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
56
System Architecture
Paolo Livi et al.
• 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 μA
57
System Architecture
16 channel bias and read out
16 „slots“ for
on-chip nanowires
Paolo Livi et al.
58
System Architecture
Nanowire Sensor Chip
CMOS Readout Chip
Paolo Livi et al.
V
DS
= 200 mV
sigma-delta modulator
read-out of 4 Si-NW, 9.-10. Nov. 2011
59
Working System
Paolo Livi et al.
60
Thanks to....
Michel Calame
Uni Basel
physics
Oren
Knopfmacher
Wangyang Fu
Alexey Tarasov
Christian
Schönenberger
Beat Ernst
EPFL
Adrian Ionescu Kristine Bedner
Bernd
Dielacher
Jolanta Kurz Uwe Pieles
Andreas
Hierlemann
Paolo Livi
Arjan Odedra
Sara Rigante
Mohammad
Najmzadeh
Janos Vörös
Robert
MacKenzie
Yihui Chen
Birgit
Päivänranta
Vitaliy
Guzenko
Christian
David
ETHZ
UniBas
pharma
Jens Gobrecht
PSI
D-BSSE
FHNW
Matthias Sreiff
Sensirion
Mathias Wipf
Renato
Minamisawa
Ralph Stoop
Floriian Binder

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