Performance Limits of Nanobiosensors

M. Alam and P. Nair Purdue University West Lafayette, IN alam@purdue.edu

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A Simple Idea .
An array Individual sensor Capture Probe

Q1

C A G A T

Conductance (G)

ts response time
G G0

Q1

A T G C A T T A

Q2

Time
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 with remarkable results

aM

fM

pM Recently Si-NW/CNT

nM

mM

In the future .. Nanodots ?

Historically ChemFET/IsFET

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Electrostatics ?
ISFET Nanosensor

Electrostatics explains a factor of 2-5, not 2-5 orders of magnitude change in sensitivity !
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Geometry of Diffusion

0 ts

MD

~ kD

Ref. APL, 88, 233120, 2006 Program is in www.nanohub.org

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Diffusion-Capture Model

dN = kF ( N0 N ) s kR N dt kF N0 s

d = D 2 dt

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Diffusion Capacitance
W

D n = 0
2

I = C0 ( 0 s )

D C0 = (Planar) W 2 D = (NW) log (W + a0 /a0 ) = 4 D a (W + a0 )

1 0 1

(ND)

C0 =

(Planar) (Cylinder) (Sphere)

s 0

= 0
2

= =

Q = C0 (0 s )

2 log (W + a0 /a0 ) 4 a (W + a0 )
1 0 1

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Cumulative Capture

I = C0 ( o s )

s 0
D W 2 D = log (W + a0 /a0 ) = 4 D
a0 1 (W + a0 ) 1

dN I=A = Ak F N 0 s dt

A 1 N ( t ) = 0t + C0 k F N 0

C0 =

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Diffusion Distance
ISFET (n = 1) Nanowire sensor (n = 2) Nanosphere sensor (n = 3)

W=(2Dt)1/2

W=(4Dt)1/2

W=(6Dt)1/2

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Time dependent capture

A 1 N ( t ) = 2t + Ct k F N 0

2 1
Ct = = log =
1 0

W (t ) =

2 nDT

D C0 = W 2 D = log (W + a0 /a0 ) = 4 D
a0 1 (W + a0 ) 1

D 2 Dt 2 D 4 Dt + a0 /a0 4 D 6 Dt + a0

)
1

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Pretty good approximation .

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Scaling Law
N (t ) = NS A 1 = 0t + Ct k F N 0
1

Ct = = log =
1 0

D (Planar) 2 Dt 2 D 4 Dt + a0 /a0

(NW)

4 D 6 Dt + a0

0ts

MD

~ kD

(ND)

0ts

0.5

~ NS

2 D

0ts ~

N S a0

0ts ~

N S a0

Response is dictated by geometry of diffusion !

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Limits of Sensor Response

0ts ~

N S a0

(SiNW) (Planar)

0ts

0.5

~ NS

2 D

100s

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Planar vs. NW Sensor

0W/a0 0
W= (2Dt)1/2 W= (4Dt)1/2

0ts

0.5

~ NS

2 D

0ts ~

N S a0

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NW vs. Nanodot Sensors

(Nanodot)

0ts ~

N S a0

(SiNW) N a 0ts ~ S 0

(Planar)

0ts

0.5

~ NS

2 D
100s

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Finite Size Effects: 2.x Dimension ?

Shorter cantilever should capture more protein ..

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A Puzzle and its resolution

We assumed . Actually

0.5 0.4 0.3

0.4

0.3

0.2

0.2
0.1

0.1 0 50 0 -20 -50 -40 20 0

0 50 20 0 0 -20 -50 -40

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Simulation supports experiment

dN = kF ( N 0 N ) s kR N dt kF N0 s

d = D 2 dt

Gupta, Nair, et al. PNAS, 13, 13362, 2006

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 with remarkable results

aM

fM

pM Recently Si-NW/CNT

nM

mM

In the future .. Nanodots

Historically ChemFET/IsFET

0ts M ~ k D ?
D

Composites more sensitive than planar, but less than NW (A. Star, PNAS,103, 4,921, 2006)
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Composites of Si-NW & CNT (Diffusion in 1.x Dimensions)

Grow on high temp. substrate

Disperse in solvent Spread on soft substrate

Si-NW

CNT

Nanosys Inc. Igal Schatz, Polymer Physics Review, 2005

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Transition among integer dimensions

2 D C= log[sinh(2 WP)/ a0 P ]
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2D to 1D Transition
Initially 2D
N(t) (#/m)
10
5

Numerical Analytical

10

1D 2D

10

-5

10

-5

Time (s)

10

10

Eventually 1D

Planar

NW

100s

Dimensionality changes with time!

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Fractal Dimension of Composites

10
4

log (N)

10

h=2 h=64 h=8 h=4 h=32 h=16

5
4 3 2 1

Slope=F.D.
10 0 10
0 2 4

10

10

log (1/h)

2
0 1 2 3 4 5 6

1.8 1.6

DF

1.4 1.2 1 0

C = 5.717

Ninad Pimparkar by Box Couting Method

10

15

S [1/m ]
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Fractional Diffusion on Fractal Surface

Cantor Sensor

0ts

MD

~ kD

M D = 1 / D!
2D

N
2D 1D

1D

Planar

NW

100s

time Dimensionality changes with time! An example of Geometrical Frustration.

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A Femto-Molar Sensor ?

2-4 nm
C G

0ts ~

N S a0

A T G C A T T A

D
C(T)/bp0.6-0.7

LNA/PNA-DNA

Smaller radius Shorter base-pair Higher temp (diffusion/Conjugation)

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On Growth and Form

Everywhere Nature works true to scale, and everything has a proper size accordingly," wrote Thompson. "Cell and tissue, shell and bone, leaf and flower are so many portions of matter, and it is in obedience to the laws of physics that their particles have been moved, moulded and conformed."

Lifes Other Secret by Ian Stewart

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Biomimetic design ?
Squid Axon Red Blood Cell

Hodgkin-Huxley, 1952

Efficiency of cells and sensitivity of biosensors .

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Summary
aM fM pM nM M M

0ts

1/ D

~ kD

Reaction-diffusion model Analogous systems Geometry of diffusion Proteins on cantilevers Fractal surface/fraction diffusion Geometrical frustration Percolation vs. fractal dimension Bio-mimetic design

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Questions & Answers

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Fractional Diffusion on Fractal Surface

Cantor Sensor

2D

N
2D 1D

1D

Planar

NW

100s

time Dimensionality changes with time! An example of Geometrical Frustration.

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Ensemble Average and fM Detection

1000s

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Pretty good approximation .

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