Specific Protein Binding Sensor using SWNT (case 1)

Electrical Sensing of Biomolecules based Nanomaterials and Carbon Nanotubes

CNT w/ Protein

AFM image

Department of Chemistry Pohang University of Science and Technology Hee Cheul Choi

Star. A, et al. Nano. Lett. 2003, 3, 459

PEI & PEG

Protein Sensor using SWNT (case 2) Individual SWNT device

CE : Pt

RE : Ag/AgCl

PBS

A,B : #1 & #2 : p-type, #3 : metallic SWNT C : before D & E : after the introduction of the protein(cytochrome c) sol’n

Æ Protein adsorption does not change slop but VTh (200 μM)

Boussaad. S, et al. Chem.Comm. 2003, 1502.

P-type SWNT

Specific Protein Binding Sensor using SWNT (case 2)

Glucose Sensor using SWNT (GOx)

H2O2

O2 gluconic acid glucose

Linking molecule : pyrene group

AFM image

Besteman. K, et al. Nano. Lett. 2003, 3, 727 Chen. R, J, et al. PNAS. 2003, 100, 4984

Specific Protein Binding Sensor using SiNW biotin-modified SiNW

streptavidin

DNA Sensor using SiNW 1 : buffer 2 : 60 fM WT DNA →

G (nS)

1,3 : DNA free sol’n 2,4 : 100 fM MU DNA ↓ Modified SiNW

Modified SiNW ↑ 1, 3 : buffer

Unmodified SiNW (A) Yellow : sensor device Green : microfluidic channel (B) PNA(peptide nucleic acid) surface (C) PNA-DNA duplex

2 : 250 nM streptavidin

Hahm. J, et al. Nano. Lett. 2004, 4, 51

Cui. Y, et al. Science 2001, 293, 1289

1, 3 : buffer 2 : 3 μM m-antibiotin

1 : buffer 2 : bovine IgG 3 : 3 μM m-antibiotin

Static system

Flowing (buffer) system

Single Virus Sensor using SiNW Microfluidic Channel (100 virus particles per μl)

50 virus particles per μl

Influenza A virus

anti-influenza type A antibody anti-adenovirus group antibody Introduce 1: adenovirus 2 : influenza A 3 : buffer 4 : 1 : 1 mixed adenovirus & influenza A

anti-hemagglutinin for influenza A anti-adenovirus group Ⅲ

Single Virus Binding Selectivity

Patolsky. F, et al. PNAS. 2004, 101, 14017

Application 2 : DNA array detection

Resistance (ohms)

Part Ⅱ

Park. S, et al. Science 2002, 295, 1503

What applications carbon nanotubes will contribute?

Forms of Carbon

Electromagnetic Shield coating

Field emission devices

Diamond

Graphite

Ray Baughman, UT Dallas

C60

Carbon nanotube

Strong materials

Structure of carbon nanotubes

Representatives of carbon nanotubes

• Nanotubes consist of graphene sheets of carbon • Rolled into a cylinder

Multi-walled (MWNT)

Single-walled (SWNT)

• Some with multiple concentric cylinders Graphite

Sumino Iijima

Single-walled nanotube (SWNT)

Multi-walled nanotube (MWNT)

Richard Smalley

SWNTs are all C molecular wires and excellent quasi 1D systems for basic work (synthesis, materials science and physics) and potential applications

Diameter Control: Catalytic Nanoparticles Derived in Apoferritin Templates (d~1-3 nm)

How do SWNTs grow?

Nanotubes at various stages of growth

• Particle size ~ tube diameter • Catalytic particles (active end) remain on support • The other end is dome-closed • Base growth (differs from the VLS growth mode) Y. Li, et al.,J. Phys. Chem., 105, 11424, 2001

Diameter Control: Catalytic Nanoparticles Derived in Dendrimer Templates (d~1-2 nm)

Nanotubes Grown From Dendrimer Templated Nanoparticles

Fe(III)/G6OH PAMAM

G6OH PAMAM

Fe2O3 Nanoparticle on SiO2

Sorption of Fe(III)

CVD 1 mm

Fe2O3

Calcination Substrate

5 nm

CVD growth Substrate

250 nm 1.3 nm

10 nm Choi, H. C. et. al J. Phys. Chem. B 2002, 106, 12361.

• Diameters: 1-2 nm • (1-5 nm with conventional supported catalyst)

A Simple Approach to Monolayer Catalytic Nanoparticles: Clean Tube Films

NH2OH

Fe(III)

OH

OH

Applications

Iron oxide nanoparticle

• AFM tip for high resolution images and fabrication • Electrical devices • Electro-mechanical devices • Gas and biosensors

OH

Calcination SiO2

SiO2

500 nm

1 μm

250 nm

Choi, H. C. et al., Nano. Lett. 2003, 3, 157.

For better resolution

Nanotube at the apex of Si tip - Direct growth for SWNT - Glue attached for MWNT SWNT

MWNT Nature 398,761-762, 1999 PNAS 97, 3809-3813, 2000

Immunoglobin G (IgG) - consists of 4 polypeptide chains (Y-shpe) - Two antigen binding fragments (Fab) - One Fc site

J. Am. Chem. Soc. 120, 603-604 (1998)

Tube deflection and Conductance change

Deflection and corresponding conductance changes: “reversible”

Carbon nanotube based Field Effect Transistors (SWNT-FETs) Ti/Au SWNT

HP4156 Semiconductor Analyzer

Vg

Vd

Vs

P-type silicon wafer 500 nm - 2 mm SiO2

10 mm 1 mm

Integrated Nanoelectronics: Nanotube Transistor Arrays with Local W/ SiO2 gates

I-Vg characteristics of SWNT-FETs

VSD

Mo

iSD -+ -+ -+ -+ -+

SiO2

30

W S

25

+-Vg Vg

I(nA)

W gate

Si

20

50 µm

500 µm

D

15 10 5 Applied bias = 10 mV

0 -10

-5

0

5

10

¾ Derived by patterned growth of nanotube arrays ¾ Percentage of semiconducting tubes: ~ 70% by CVD ¾ High yield of transistors ¾ Ability in obtaining p- and n- arrays on same chip for Complementary Devices

Vg(V)

Nanotube Ring Oscillators & Logic Gates

Vout (volts)

-2.5

Vout p

n

-1.5

p

n

-1.0

p

n

-2.0

VDD

• Orders of magnitude conductance response

-0.5 0

10

20

30

Time (ms)

0,0

-1.0

0,1

1,1

• Room temperature

Vout

-1.5 Vout (volts)

Nanotube Chemical Sensors

p

n

p

n

• NO2: near chemisorption

1,0

p

• NH3: physisorption

A

-0.5

n

AND gate

B

0.0 0

20

40 Time (s)

60

VDD

80

Javey et al. Nano Lett., 2002

Science, 287, 622, 2000

Nanotube sensor array with 100% yield

H2 sensing with SWNT/Pd single device

4μm

300μm

3.0 I(μΑ)

~ 5 Å Pd

2.5 2.0

40μm

1.5 -10

0 Vg (V)

10

• Grow multiple tubes for each device in a large array • Semiconducting tubes dominant (70%) • Excellent electrostatic gating and chemical gating sensitivity J. Kong et. al., Adv. Mater. 13, 1384, 2001

Multiplex-functionalized sensor array capable of detecting multiple molecules in a gas mixture

100ppt

0.0 -ΔG/G0

4.0

I(μΑ)

3.5 3.0

0.1

• NO2 sensing: Down to 100 ppt sensitivity • Sticking coefficient PEI/tube ~ 0.3 No PEI/tube ~0.001

200 500 1ppb

0.2 0.3

2

0.4

2.5

8

Nafion coated 7 6

0.5 0

-10

PEI coated

I(μΑ)

Enhanced sensitivity of NO2 detection for polymer (PEI) coated n-type devices

• Large sensor arrays obtained (100% yield, low noise)

0 Vg (V)

10

2000 4000 6000 8000 t(s)

Enhanced selectivity as well: No response to NH3, CO, CO2, H2, CH4, O2

-ΔG/G0

I-Vg of n-type device

0.5

0.5

0.4

0.4

0.3

0.3

0.2

0.2

0.1

0.1 0.0 0

-10 -20 Vg (V)

PEI coated

5 4

[NO2](ppb) 2 4 6 8 10

0.0

NH3 NH3 100ppm 500ppm

NO2 1ppm

3

Nafion coated • Micro-spotting used for coating different devices with different polymers

2 0

400 800 1200 1600 t(s)

P. Qi, et al, Nano Lett. 3, 347, 2003

CNT-FET device for biosensor applications

CNT-FET as a smart sensor

-Teflon based electrochemical cellCounter electrode (Pt) Reference electrode (Ag/AgCl)

Conventional CNT-FET 200 μm

- Change of IDS by the effect of VGS - VGS by electric field

Bias (V)

5 μm

CNT-Chemical Effect Transistor (CET) - Change of IDS NOT by the effect of VGS - Why not by chemical effects? * Charge transfer from molecules to CNT

50 μm

Hydrophobic/vdW anchoring of Tween20/PEG

Non-specific interaction of SWNT with proteins

50

A repelled OH HO

200 nm

(B

QCM Signal Δ F (Hz)

1 nM 10 nM

0

O O

Streptavidin, Protein A, Glucosidase, Bovine Serum Albumin, IgG…

O

OH HO

x

O O O

Turns out to be generic:

50 .1 nM

Ow O

x

O O O

yOH

O O

z

Ow O

O

yOH

z

0

100 nM SA

50

QCM Δ F(Hz)

Δ F (Hz)

SA

100 nM BSA

100 nM SpA

rinse

QCM Signal

(A

-50

.05% Tween 20

0 -50

-100

-100

rinses

-150 -200

-150

0

4

8

t/10

12

3

16

C

(s)

-200 0

1

2

3

4

5

3

100 nm

100 nM

B

1 μM Streptavidin

-50

t /10 (s) 200 nm

rinses

I

II

III

™Non-covalent irreversible adsorption ™Water solubility, highly stable

-100

™Protein resistant ™Tween 20 & Pluronic block copolymer P103 are the best

-150

C E

-200 0

2

4

6

8 3

t/10 (s)

10

12

14

16

Chen et al, PNAS 2003, 100, 4984

Selective electronic biosensor

Origin of the conductance change Where does the conductance change come from? • Nanotube aspects: – Charge injection from biomolecules – Electric double layer field modulation caused by biomolecules • Metal-nanotube contact aspect: – Adsorbed chemical species may modulate work function level of contact metals, which consequently change the Schottky barrier height resulting in the conductance change.

Nanotube vs. metal-nanotube contact

PMMA SWNT

BSA

SiO2/Si Pd/Au evaporation

Both photolithography and electron-beam lithography can be used

.02x10 SiO2/Si

HIgG .50x10

-6

Ids (μΑ)

3.00

mPEG-SH SAM

Ids (μΑ)

CNT-FET device fabrication

2.98

s

100 nM

2.96

s s s s ss ss s ss s SiO2/Si

Lift off then Tween 20

2.94 0

Lift off

.40x10 ss

ss

SiO2/Si

SiO2/Si

S

S

S

HO

Device II

O O

800 Time (s)

1200

-6

100 nM

3.30

Ow O

x

O O O

S 11

Device I

.50x10

100 nM

-6

400

3.45

SiO2/Si OMe OMe O O n n

1.44 0

1200

Device I Metal-nanotube

100 nM

1.46

ss

OH

OMe OMe O O n n

800 Time (s)

Ids (μΑ)

ss

400

1.48

Ids (μΑ)

Lift off

-6

O

yOH

Device II Nanotube only

3.40 3.35

3.20

z

Device III

Chen, Choi et al J. Am. Chem. Soc. 2004, 126, 1563

0

400 800 Time (s)

1200

3.30 0

200

400 600 Time (s)

800

1000

Nanotube vs. metal-nanotube contact hCG

HSA .65x10

.50x10

Summary of biomolecule sensing mechanism

-6

-6

100 nM

1. hCG NSB

Pd or Au

Ids (μΑ)

Ids (μΑ)

2.60 2.40 100 nM

3.5x10

2.55

400

800 Time (s)

2.45 0

1200

-6

.50x10

100 nM

1. mPEG-SH on Pd or Au

400

800 Time (s)

1200

Ids (μΑ)

Device II Nanotube only

400 Time (s)

600

800

Device II

3.20 0

G

Effective functionalization of metal surface with appropriate chemical species will lead high sensitive and selective nanotube-biosensor.

3.25 200

Time (s)

S

Pd or Au

2. hCG NSB

3.30

3.1

S

Conductance (G) Measurement

100 nM

3.35

3.2

S

G

Time (s)

3.40

3.3

OMe OMe OMe O O O n n n

-6

3.45 3.4 Ids (μΑ)

SiO2/Si SWNT-FET

2.50

2.30 0

Device I

Device I Metal-nanotube

400

800 Time (s)

1200

Application 1 : DNA-templated CNT-FET

DNA and Protein Sensor using GC/CNTs (case 3)

DNA-templated CNT FET & metallic wires contacting it

Chronopotentiometric signals

glassy carbon electrode (GC)

CNT

DNA

protein

SEM image

A (DNA) : 10 pg/mL target oligonucleotide B (protein) : 80 pg/mL IgG (a) single ALP tag (b) CNT-multiple ALP tags (c) CNT-ALP tags modified GC electrode 50 μL α–naphthyl PBS sol’n(50 mM) w/ enzymatic rxn Keren. K, et al. Science. 2003, 302, 1380

Magnetic beads-DNA-CNT + 10 pg/mL target sample

Wang. J, et al. J. Am. Chem. Soc. 2004, 126, 3010.