NIRT: Molecular Sensing and Actuation by CMOS Nonvolatile Charges with Independently Addressed Nanoscale Resolution

Edwin C. Kan, F. A. Escebeo, A. Lal, J. R. Engstrom and D. A. KyserCornell University, Ithaca, NY

Single-Electron Control at RT

Floating-Gate-Based Sensors

Wafer-binding/PDMS microfluidic Detection up to 1nA/1µs pulses Wierner Signal equalization

Protein Adsorption DetectionBulk Potential

Electrolyte Diffusive Layer (~25Å): second component of Gouy-Chapman-Stern model. εr>78Electrolyte Double Layer (~5Å): first component of Gouy-Chapman-Stern model. εr>78Streptavidin (~2-19Å): analyte protein for capture. Thickness increases as binding occurs. Assume εr≈10

Biotinylated BSA (~11Å). εr≈10

3-GPS (~14Å) εr≈11.8

Native Oxide (~26Å). εr≈4.0

Cdiff

CEDL

Cstrep

CBSA

C3-GPS

Coxide

1000 1200 1400 1600 1800 2000

0.25

0.3

0.35

0.4

Time(sec)

Sen

sor S

igna

l Mag

nitu

de (V

rms)

69% coverage capture

11% coverage capture

Control data

Signal changefrom event

Addanalyte

0 0.05 0.1 0.15 0.2 0.250

0.01

0.02

0.03

0.04

0.05

0.06

Captured mass (g/cm2)

Sen

sor

resp

onse

(Vrm

s)

Measured data

Fitted data

0 5 10 15 200

5

10

15

20

Ellipsometer: analyte thickness (Angstroms)

Sen

sor:

det

ecte

d th

ickn

ess

(Ang

stro

ms)

Measured data

Fit for measured data

Ideal calibration curve

N

R Molecules, cells and nano-engineered structures are all immerged in biochemical fluids.

Anthrax pores (from Public Health Library)

Gold nanoshells (from N. Halas, Rice)

Functionalized SWNT (from H. Dai, Stanford)

Examples of nano-engineered structures to build interface between molecules and inorganic devices. Notice that molecular selectivity is still provided by attached organic active ends.

Charge surface of cytochrome B562Blue: anion; red: cation; yellow: h-bond; white: neutral.

Molecular structure of cytochrome B562 as an illustration

The basic device structures for nano-scale molecular interactions based on electrostatic attractive and repulsive forces by CMOS nonvolatile charges.

Our Unique Approach

Molecular Simulation

H ,T H ,T H ,T H ,T1 1 2 2 i i M. .. .. . MH a m ilto n ia n a n dTe m p e ratu re

F re e E n e rg yL a n sc a p e

H y b rid M C w ithM u lti-D im e n s io n a lR e p lic a E x c h a n g e s

... ...h y b rid M C

C H A R M M

h y b rid M C

C H A R M M

h y b rid M C

C H A R M M

h y b rid M C

C H A R M M

A generalized ensemble of M independent replicas are simulated using hybrid MC in which MD trajectories are carried out using CHARMM.

Coarse Grain

H 1

H 3

H 2

(a) Main-chain atoms of the llama HC-V domain solved by X-ray diffraction [Spinelly96]. The loops are shown as gray lines and proximal framework regions as black lines. (b) Schematic diagram of the simulation box for entropic trapping of DNA.

Atomistic

Monitoring the current over time

0.00E+00

2.00E-06

4.00E-06

6.00E-06

8.00E-06

1.00E-05

1.20E-05

1.40E-05

1.60E-05

1.80E-05

2.00E-05

0 1000 2000 3000 4000 5000 6000

Time in seconds

Id C

urr

en

tSeries1

DMEM in FBS (9ul)

ADDITION of A431 in culture media (5ul)

Addition of EGF in Culture media (2ul Drop) concentration 5ug/ml

Real-time CνMOS monitoring of a single A431 cell on the sensing gate coated with poly-l-lysine. A431 is added to the DMEM in 10% FBS media solution after the surface is stabilized (1). The cell moves to the poly-l-lysine (2), seals (3) and immobilizes (4). EGF is then added (5), where receptor interaction is confirmed with fluorescence images. Cell life is monitored on the witness sample going through the same process by calcein staining.

(1) (2) (3) (4) (5)

VGS = 10VVDS = 5V

A431 SEM after critical point dry

A431 fluorescence image: 3 mins after adding EGF

A431 fluorescence image: 15 mins after adding EGF

Calcein staining to monitor cell life

Cell A431 Sensing: EGFR

DMEM/FBS Stablize

Cell moves to p-l-lysine

Cell surface seals

Cell immob-ilize

EGF inter-action

A431Poly-l-LysineSensing gateFloating gate

ID

VGS

T

sgsggssgddcgcgFG

sggdgsbdepoxT

dgdsgsT

thth

C

VCCVCVCVQV

CCCCCCC

VCVCQC

VV

)||(

)(1

0

Control Gate

Control Oxide

Sensing Gate

Tunnel OxideInterpoly Oxide

Source Drain

Floating gate

Sensing GateSource

Drain

Control Gate

Floating gate

Interpoly Oxide

Sensing Gate

Pt ElectrodeAg/AgCl Electrode

Voltage Pulse Generator

Microfluidic Chamber

-2 -1 0 1 2

x 10-4

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Time (10-4 s)

Sig

nal

(V

or

A

)

Input Pulse

Id Averaged

Id Equalized

Id Wiener equalization

Input

Id Averaged

-20 -10 0 10 20 30 40 50-15

-10

-5

0

5

10

Control sample

C60

1-

EC60

~ 1.3 eV

C60

2-

EC60

~ 0.8 eV

C60

3-

EC60

~ 0.8 eV

room temperatureV

FB [

V]

Programming Voltage [V]

C601

EC60

1.3eV

C602

EC60

0.8eV

C603

EC60

0.8eV

-0.55V

-0.65V

-3.36V

-1.69V

-1.77V

-3.31V

-3.27V

Sensing Gate

Native OxideSilane

BlockerAntibody

Antigen

Features 100% CMOS integration Specificity by sensing gate coating: pressure, proteins… Nonlinear response: high sensitivity and large range Noninvasive: no need of analyte reference electrode

Applications In vivo sensing Monitoring cell events Specific protein sensing Sensor network

Sensing Gates

CMOS

CMOS Transistor

10-2

100

102

10-10

10-5

Log frequency (Hz)

Lo

g m

agn

itu

de

(Vrm

s)

Sampled data

1/f spectrum

1/f2 spectrum

1/f α behaviorNoise floor

DFT calculation

C60

Control Gate

DrainSource Sensing Channel

SiO2

p++ Si

PdPd SWCNT

Nanocrystal

ttop

-3 -2 -1 0

10-10

10-9

10-8

Gate Voltage (V)

after charging

after discharge

Control Gate Voltage (V)

Dra

in C

urre

nt (

A)

T=300K Long-term memory window

Short-term single-electron sensitivity

Initial memory window

1 m

Nanotube

Au leads

Au leads

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

1 2 3 4 5

Sample Fluids

d1i-

m N

orm

polysiliconpoly(vinyl acetate)poly(vinyl butyral)poly(ethylene -co- vinyl acetate)poly(vinyl chloride)

Nor

mal

ized

C

SG(d

1 i-m

)

DI water 50 M 0.005M 0.05 M 0.5M

0.0

2.51

2

34

5

Mixture

0.5 M NaCl

0.05 M KCl

Conventional Nanostructure Approach: Space Holder

Motivation