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
