nanowire fet biomolecular sensors - cmu.edu · pdf file29-04-2009 · nanowire fet...
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11NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Nanowire FET Biomolecular
Sensors
Mark ReedYale University
Nanowire FET Nanowire FET Biomolecular Biomolecular
Sensors Sensors
Mark ReedMark ReedYale UniversityYale University
Departments of Applied Physics and Electrical Engineering Yale Institute for Nanoscience and Quantum Engineering
with: Eric Stern, David Routenberg, Erin Steenblock, Alek Vacic, Nitin Rajan, Prof. Tarek Fahmy
Thanks to: Jin Chen, James Klemic, Daniel Turner-Evans, Pauline Wyrembak , Cathy JanLabs of Profs. Ronald Breaker, Andrew Hamilton, Tarek Fahmy
Departments of Applied Physics and Electrical Engineering Departments of Applied Physics and Electrical Engineering Yale Institute for Nanoscience and Quantum EngineeringYale Institute for Nanoscience and Quantum Engineering
with: Eric Stern, David Routenberg, Erin Steenblock, Alek Vacic, Nitin Rajan, Prof. Tarek Fahmy
Thanks to: Jin Chen, James Klemic, Daniel Turner-Evans, Pauline Wyrembak , Cathy JanLabs of Profs. Ronald Breaker, Andrew Hamilton, Tarek Fahmy
22NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
What I won’t talk about todayWhat I won’t talk about today
plasmonicsplasmonics
mesoscopicsmesoscopics
nanowire materials nanowire materials & devices& devices
DNA DNA sequencing sequencing
devicesdevices
physics of physics of scaledscaleddevicesdevices
molecularmolecularelectronicelectronictransport, transport,
IETS IETS
33NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Current Macromolecular SensingCurrent Macromolecular SensingLabeled sensingLabeled sensing
DNA sequencing, radiotagDNA sequencing, radiotag DNA array, fluorDNA array, fluor ELISA: Indirect fluorELISA: Indirect fluor
Suspended cantileverSuspended cantileverSurface plasmon resonanceSurface plasmon resonance Electrical : ISFETElectrical : ISFET
Unlabeled sensingUnlabeled sensing
44NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Buffer BSA PSA
390
385
380
I (n
A)
5004003002001000Time (s)
PSA
In2O3 NW
rdQdI
I1~1
Si
Au/Ti
SiO2
PSA
PSAantibody
Linker
PSA
NW/SWNTISFETs ISFETs detection limits detection limits typically ~ typically ~ µµMM
(C. Zhou, USC)
10nm diameter GaN NW
Nanowire biosensorsNanowire biosensors(unlabeled detection)(unlabeled detection)
55NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Silicon-on-insulator (SOI) CMOS NanowiresSilicon-on-insulator (SOI) CMOS Nanowires
0 -5 -10 -15
0
-1
-2
-3
I SD (A
)
VSD (V)
VG=-40V
VG=0V
300K, dry25nm SOI
NatureNature 445, 445, 519 (2007)519 (2007)
66NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
0 -5 -10 -15
0
-1
-2
-3
I SD (A
)
VSD (V)
0 -10 -20 -30 -401f
100f
10p
1n
100n
|I SD (A
)|
VGD (V)
p-type accumulation mode (backgate)p-type accumulation mode (backgate)
∆VG=1V300K, dry
w=50nm, t=25nm
VG=-40V
0V
VSD=-1V
30 10040
100
400
Mob
ility
(cm
2 /Vs)
Temperature (K)
HallDrift
w = 300 nmt = 25 nm
µµmax max = 139 cm= 139 cm22/V/V--ss
Fully depleted; n0 ~ 1x1015 cm-3
µ µ = 54 cm= 54 cm22/V/V--ss
77NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
1/f noise of nanowires1/f noise of nanowires
InAs
SnO2
Nfα=
IS HI
2
ITRS Si SOI NWαH = 1.3 x 10-4
88NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
NW Sensitivity Scaling with Size : pH SensingNW Sensitivity Scaling with Size : pH Sensing
large: large: ww = 1000 nm; = 1000 nm; tt = 80 nm= 80 nmsmall: small: ww = 100 nm; = 100 nm; tt = 25 nm= 25 nm
0 100 200 300 400 500 600
10n
100n
1
|I SD (A
)|
Time (s)
largesmall
8.0
7.5
7.0
6.5
6.0
6.5
7.0
7.5
8.0
0 100 200 300 400 500 600
10n
100n
1
|I SD (A
)|
Time (s)
largesmall
8.0
7.5
7.0
6.5
6.0
6.5
7.0
7.5
8.0
0 5 10 15 20 250
20
40
Sens
itivi
ty
Inverse Radius (µm-1)
NB device RIE device
00,
2nN
RII s
VSD
SD
SD
α⋅=
∆
pHdecade1 is response max. decademV60slope ldSubthresho
pHmV60potentialNernst
∴=
=
99NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Fluid ConsiderationsFluid Considerations
10-15 10-14 10-13 10-12 10-11 10-10 10-91E-6
1E-4
0.01
1
100
10000
1000000
1E8
1E10
1E12
# M
olec
ules
/Min
C0 (M)
xx
xx
Silicon-specificfunctionalization
Nonspecificfunctionalization
10-15 10-14 10-13 10-12 10-11 10-10 10-91E-6
1E-4
0.01
1
100
10000
1000000
1E8
1E10
1E12
# M
olec
ules
/Min
C0 (M)
xx
xx
Silicon-specificfunctionalization
Nonspecificfunctionalization
Nano LettNano Lett 55, 803 (2005) , 803 (2005)
xx = microfluidics= microfluidicsScienceScience 293, 293, 12891289 (2001)(2001)
xx = mixer (resorvoir)= mixer (resorvoir)NatureNature 445, 445, 519 (2007)519 (2007)
020
2
Cudz
CdDJ zz +−=0
1010NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Biotin-Avidin & Streptavidin SensingBiotin-Avidin & Streptavidin Sensing
nn pp--type accumulation mode, type accumulation mode, biotinylated NW devicebiotinylated NW device
nn avidin avidin uu positive charge positive charge uu ⇒⇒ current decreasecurrent decrease
nn streptavidin streptavidin uu negative chargenegative chargeuu ⇒⇒ current increasecurrent increase
nn poly(ethylene glycol) poly(ethylene glycol) (PEG)(PEG)--ylated device, ylated device, quenched avidin controlsquenched avidin controls
-20 0 20 400
100n
200n
300n
|I SD (A
)|
Time (sec)
StreptavidinQuenched S-AvPEGylatedAvidin
1 nM protein in0.1X PBS (λD ~ 2.2 nm)
analyteanalyte
receptorreceptor(biotin)(biotin)
NatureNature, , 445445, 519 (2007), 519 (2007)
1111NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Sensitivity: Concentration DependenceSensitivity: Concentration Dependence
nn initial S/N initial S/N ~ 140 (@10fM)~ 140 (@10fM)
⇒⇒ <100 aM limit<100 aM limit(< 3 fg/ml)(< 3 fg/ml)
((1 aM = 30 1 aM = 30 molecule per mmmolecule per mm33))
-20 0 20 40 60 80
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
2.2
Nor
mal
ized
|ISD
(A)|
Time (sec)
1 nM 10 pM 100 fM 10 fM
DC, ambient
1212NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
DNA sensing: criss-crossDNA sensing: criss-cross
•• Capture1 is the Capture1 is the complementary strand of Probe1;complementary strand of Probe1;•• Capture2 is the Capture2 is the complementary strand of Probe2complementary strand of Probe2
Surface: Capture2Surface: Capture2
-50 0 50 100 150 200
2.0
2.2
2.8
3.0
3.2
|I SD (A
)|
Time (sec)
Probe 1 Probe 2
-50 0 50 100 150 200500.0n
1.0
3.0
3.5
|I SD (A
)|
Time (sec)
Probe 1 Probe 2
SS DD
S D
Surface: Capture1Surface: Capture1
1313NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Debye Screening ConsiderationsDebye Screening Considerations
( ) 2/1241
∑=
i iiB
Dzl ρπ
λ
.01X
.1X
1X
for 0.1 mM PBS, for 0.1 mM PBS, λλDD ~ 2.2nm~ 2.2nm
b
0 100 200 300600.0n
800.0n
1.0
|I SD (A
)|
Time (s)
t = 0:.01X AloneS-Av (.01X)
.1X 1X .01X TCEP.01X
0 100 200 300600.0n
800.0n
1.0
|I SD (A
)|
Time (s)
t = 0:.01X AloneS-Av (.01X)
.1X 1X .01X TCEP.01X
b
0 100 200 300600.0n
800.0n
1.0
|I SD (A
)|
Time (s)
t = 0:.01X AloneS-Av (.01X)
.1X 1X .01X TCEP.01X
0 100 200 300600.0n
800.0n
1.0
|I SD (A
)|
Time (s)
t = 0:.01X AloneS-Av (.01X)
.1X 1X .01X TCEP.01X
Stern Stern et al, Nano Lett. et al, Nano Lett. 77, 3405 (2007), 3405 (2007)
(cleave)
add S-Av .01X
Controlno S-Av
1414NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Protein Assay: Antibody-Antigen Specificity Protein Assay: Antibody-Antigen Specificity Surface: Surface: αα--mousemouse--IgAIgA
100 fM mouse100 fM mouse--IgG/IgA in 1.5 mM bicarbonate (IgG/IgA in 1.5 mM bicarbonate (λλDD ~ 6.8 nm)~ 6.8 nm)
-20 0 20 40 60100n
125n
150n
175n
200n
225n
250n
275n
|I SD (A
)|
Time (sec)
mouse-IgAmouse-IgGPEGylated
100 fM100 fM
1515NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Unlabeled Cellular DetectionUnlabeled Cellular Detectionnn Most cells (including Most cells (including
pathogenic) release Hpathogenic) release H++
in response to specific in response to specific stimulationstimulation
H+ H+
H+H+
H+
H+
H+
Nat Rev ImmunolNat Rev Immunol 33 (2003) 973(2003) 973
1616NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
H+ H+
H+H+
H+
H+
H+
-20 -10 0 10 20 30 40 50400n
600n
800n
1
|I SD (A
)|
Time (s)
anti-CD3 to:normalinhibited
(Genistein)
C57BL/6 (B6) mouse splenocytes
RealReal--time measurement of cell time measurement of cell immune response dynamicsimmune response dynamics
ISD
time
Real-time live cellular response – T-lymphocyte activationReal-time live cellular response – T-lymphocyte activation
1717NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
Transgenic peptide-specific MHC T-cell response
Transgenic peptide-specific MHC T-cell response
-25 0 25 50 75400.0n
600.0n
800.0n
1.0
1.2
1.4
|I SD (A
)|
Time (sec)
H-2Kb-SIINH-2Kb-SIY
-25 0 25 50 75400.0n
600.0n
800.0n
1.0
1.2
1.4
|I SD (A
)|
Time (sec)
H-2Kb-SIINH-2Kb-SIY
-25 0 25 50 750.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
|I SD (A
)|
Time (sec)
H-2Kb-SIINH-2Kb-SIY
-25 0 25 50 750.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
|I SD (A
)|
Time (sec)
H-2Kb-SIINH-2Kb-SIY
OTOT--1/2C transgenic murine CD81/2C transgenic murine CD8++ TT--cells cells
OTOT--1 reacts to H1 reacts to H--2K2Kbb--SIIN, not HSIIN, not H--2K2Kbb--SIYSIY
2C reacts to H2C reacts to H--2K2Kbb--SIY, not HSIY, not H--2K2Kbb--SIINSIIN
OT-1
2C
Model system for detecting autoimmune diseases and cancerModel system for detecting autoimmune diseases and cancerStern Stern et alet al, , Nano Lett. Nano Lett. 88, 3310 (2008)., 3310 (2008).
OTOT--11 2C2C
HH-- 2
K2Kbb --
SIY
SIY
HH-- 2
K2Kbb --
SIIN
SIIN
XX
1818NanoForum09 Las Vegas, NV ANanoForum09 Las Vegas, NV April 29, 2009 M. Reed (Yale) pril 29, 2009 M. Reed (Yale)
SummarySummarySummary
nn CMOSCMOS--integrable integrable ““NWsNWs””uu LabelLabel--free sensing to aM resolutionfree sensing to aM resolution
Enables systemEnables system--level integration level integration uu Macromolecular assaysMacromolecular assays
nn RealReal--time cellular immune response time cellular immune response uu Applicable to simple, pointApplicable to simple, point--ofof--care diagnosticscare diagnostics
(all simple DC, ambient)(all simple DC, ambient)uu Immune response dynamicsImmune response dynamics
nn Rich area for novel device designs, applicationsRich area for novel device designs, applications
nn The challenge:The challenge: sensing with physiologic solutions (blood)sensing with physiologic solutions (blood)
AlturaAlturaDiagnosticsDiagnostics
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