Nanowire FET
Biomolecular
Sensors
Mark Reed
Yale University
Departments
Departments of
of Applied
Applied Physics
Physics and
and Electrical
Electrical Engineering
Engineering
Yale
Yale Institute
Institute for
for Nanoscience
Nanoscience and
and Quantum
Quantum Engineering
Engineering
with:
with: Eric
Eric Stern,
Stern, David
David Routenberg,
Routenberg,
Erin
Erin Steenblock,
Steenblock, Alek
Alek Vacic,
Vacic, Nitin
Nitin Rajan,
Rajan,
Prof.
Prof. Tarek
Tarek Fahmy
Fahmy
Thanks
Thanks to:
to: Jin
Jin Chen,
Chen, James
James Klemic,
Klemic, Daniel
Daniel
Turner-Evans,
Turner-Evans, Pauline
Pauline Wyrembak
Wyrembak ,, Cathy
Cathy Jan
Jan
Labs
Labs of
of Profs.
Profs. Ronald
Ronald Breaker,
Breaker,
Andrew
Hamilton,
Tarek
Andrew Hamilton, Tarek Fahmy
Fahmy
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
1
What I won’t talk about today
plasmonics
nanowire materials
& devices
mesoscopics
DNA
sequencing
devices
molecular
electronic
transport,
IETS
NanoForum09
Las Vegas, NV
physics of
scaled
devices
April
April 29, 2009
M. Reed (Yale)
2
Current Macromolecular Sensing
Labeled sensing
DNA sequencing, radiotag
DNA array, fluor
ELISA: Indirect fluor
Unlabeled sensing
Surface plasmon resonance
NanoForum09
Suspended cantilever
Las Vegas, NV
April
April 29, 2009
Electrical : ISFET
M. Reed (Yale)
3
Nanowire biosensors
(unlabeled detection)
PSA
PSA
(C. Zhou, USC)
PSA
PSA
antibody
Linker
1 dI 1
~
I dQ r
NW/SWNT
SiO2
Si
In2O3 NW
390
I (nA)
ISFETs
detection limits
typically ~ µM
Au/Ti
385
BSA
Buffer
380
0
100
200
PSA
300
Time (s)
400
500
10nm
diameter
GaN NW
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
4
Silicon-on-insulator (SOI) CMOS Nanowires
Nature 445, 519 (2007)
VG=-40V
ISD (A)
-3ٛ
300K, dry
25nm SOI
-2ٛ
-1ٛ
0
0
-5
-10
VSD (V)
NanoForum09
-15
VG=0V
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
5
p-type accumulation mode (backgate)
|ISD (A)|
∆VG=1V
300K, dry
w=50nm, t=25nm
VSD=-1V
1n
10p
100f
-2ٛ
1f
0
-1ٛ
-10
-20 -30
VGD (V)
400
0V
0
-5
-10
-15
VSD (V)
Fully depleted; n0 ~ 1x1015 cm-3
µ = 54 cm2/V-s
µmax = 139 cm2/V-s
-40
Hall
Drift
2
0
Mobility (cm /Vs)
ISD (A)
-3ٛ
100n
VG=-40V
100
40
w = 300 nm
t = 25 nm
30
100
Temperature (K)
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
6
1/f noise of nanowires
SnO2
InAs
ITRS
NanoForum09
Las Vegas, NV
SI
αH
=
2
I
f N
April
April 29, 2009
Si SOI NW
αH = 1.3 x 10-4
M. Reed (Yale)
7
NW Sensitivity Scaling with Size : pH Sensing
1ٛ
NB device
RIE device
8.0
7.5
7.5
100n
7.0
7.0
6.5
large
small
10n
0
40
Sensitivity
|ISD (A)|
8.0
100
6.5
20
∆I SD
I SD , 0
0
0
5
10
15
=
VSD
2 αN s
⋅
R n0
20
25
-1
Inverse Radius (µm )
6.0
200
300
400
500
600
Time (s)
large: w = 1000 nm; t = 80 nm
small: w = 100 nm; t = 25 nm
NanoForum09
Las Vegas, NV
Nernst potential = 60 mV pH
Subthreshold slope = 60 mV decade
∴ max. response is 1 decade pH
April
April 29, 2009
M. Reed (Yale)
8
Fluid Considerations
Nano Lett 5, 803 (2005)
1E12
1E10
# Molecules/Min
1E8
Silicon-specific
functionalization
1000000
d 2 C0 0
J z = −D
+ u z C0
2
dz
10000
x
100
1
x
0.01
1E-4
1E-6
-15
10
10
-14
10
-13
10
-12
Nonspecific
functionalization
10
-11
10
-10
10
-9
C0 (M)
x = microfluidics
Science 293, 1289 (2001)
x = mixer (resorvoir)
Nature 445, 519 (2007)
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
9
Biotin-Avidin &
Streptavidin Sensing
receptor
(biotin)
300n
analyte
n
n
n
p-type accumulation mode,
biotinylated NW device
avidin
u positive charge
u ⇒ current decrease
streptavidin
u negative charge
u ⇒ current increase
poly(ethylene glycol)
(PEG)-ylated device,
quenched avidin controls
NanoForum09
200n
|ISD (A)|
n
Streptavidin
Quenched S-Av
PEGylated
Avidin
100n
0
-20
0
1 nM protein in
0.1X PBS (λD ~ 2.2 nm)
Las Vegas, NV
20
40
Time (sec)
Nature, 445, 519 (2007)
April
April 29, 2009
M. Reed (Yale)
10
Sensitivity: Concentration Dependence
2.2
n
Normalized |ISD (A)|
2.0
1.8
1.6
⇒ <100 aM limit
(< 3 fg/ml)
1.4
1 nM
10 pM
100 fM
10 fM
1.2
1.0
0.8
0.6
-20
DC, ambient
NanoForum09
0
20
40
60
initial S/N
~ 140 (@10fM)
(1 aM = 30
molecule per mm3)
80
Time (sec)
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
11
DNA sensing:
criss-cross
S
D
• Capture1 is the
complementary strand of Probe1;
• Capture2 is the
complementary strand of Probe2
3.5ٛ
3.2ٛ
3.0ٛ
|ISD (A)|
|ISD (A)|
3.0ٛ
2.8ٛ
2.2ٛ
1.0ٛ
Probe 1
Probe 2
Probe 1
Probe 2
2.0ٛ
-50
0
50
100
150
200
500.0n
-50
Time (sec)
50
100
150
200
Time (sec)
Surface: Capture2
Surface: Capture1
S
NanoForum09
0
Las Vegas, NV
D
April
April 29, 2009
M. Reed (Yale)
12
Debye Screening Considerations
b
λD =
add S-Av .01X
(4πl ∑ z ρ )
B
t = 0:
.01X Alone
S-Av (.01X)
1.0ٛ
1
i
2
i
1/ 2
i
|ISD (A)|
for 0.1 mM PBS,
λD ~ 2.2nm
800.0n
.01X
600.0n
.1X
1X
.01X
.01X TCEP
(cleave)
Control
no S-Av
0
100
200
300
.1X
Time (s)
1X
Stern et al, Nano Lett. 7, 3405 (2007)
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
13
Protein Assay: Antibody-Antigen Specificity
Surface: α-mouse-IgA
275n
250n
|ISD (A)|
225n
mouse-IgA
mouse-IgG
PEGylated
200n
100 fM
175n
150n
125n
100n
-20
0
20
40
60
Time (sec)
100 fM mouse-IgG/IgA in 1.5 mM bicarbonate (λD ~ 6.8 nm)
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
14
Unlabeled Cellular Detection
n
Most cells (including
pathogenic) release H+
in response to specific
stimulation
H+
H+
+
H+ H
H+
H+
H+
Nat Rev Immunol 3 (2003) 973
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
15
Real-time live cellular response – T-lymphocyte activation
C57BL/6 (B6) mouse splenocytes
1
|ISD (A)|
800n
ISD
time
H+
H+
+
H+ H
H+
anti-CD3 to:
normal
inhibited
(Genistein)
600n
400n
-20
-10
0
H+
10
20
30
40
50
Time (s)
H+
Real-time measurement of cell
immune response dynamics
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
16
OT-1
T-cells
H-2Kb-SIIN
OT-1/2C transgenic murine
CD8+
H-2Kb-SIY
Transgenic peptide-specific
MHC T-cell response
ƒ OT-1 reacts to H-2Kb-SIIN, not H-2Kb-SIY
ƒ 2C reacts to H-2Kb-SIY, not H-2Kb-SIIN
7.0ٛ
|ISD (A)|
|ISD (A)|
2C
1.0ٛ
OT-1
3.0ٛ
X
1.2ٛ
5.0ٛ
4.0ٛ
X
1.4ٛ
b
H-2K -SIIN
b
H-2K -SIY
6.0ٛ
2C
800.0n
2.0ٛ
600.0n
1.0ٛ
0.0
-25
b
0
25
50
75
400.0n
-25
H-2K -SIIN
b
H-2K -SIY
0
25
50
75
Time (sec)
Time (sec)
Model system for detecting autoimmune diseases and cancer
Stern et al, Nano Lett. 8, 3310 (2008).
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
17
Summary
n
CMOS-integrable “NWs”
u
u
n
Label-free sensing to aM resolution
ƒ Enables system-level integration
Macromolecular assays
Real-time cellular immune response
Applicable to simple, point-of-care diagnostics
(all simple DC, ambient)
u Immune response dynamics
u
Altura
Diagnostics
n
Rich area for novel device designs, applications
n
The challenge: sensing with physiologic solutions (blood)
NanoForum09
Las Vegas, NV
April
April 29, 2009
M. Reed (Yale)
18