Transcript Molecular Sensing Using Nanofluidics

Molecular Sensing Using
Nanofluidics
A Novel solution using Nanofluidic Field Effect
Transistors
By Laura Benson, Chris Hughes, and Zac Milne
The Need
2009 NIH challenge for scientists to learn
to sequence DNA for less than $1000
 With cheap and quick access to a patients
genetic information, doctors will be able
to usher in a new level of personalized
medicine
 Ineffective treatments can be avoided and
better drugs can be developed

The current leader



The leading technology to achieve this goal
is a Nanopore based Coulter Counter
Coulter counters have been around for
more than 50 years, and are used to count
cells based on a change in current as they
pass through a pore
As each nucleobase of DNA passes through
the pore, each alters the current in a
different way, thus allowing for sequencing
Nanofluidic Field Effect Transistors

NFETs can solve two major nanopore issues

A NFET is simply a device which uses the
principals of electrokinetics to tune the
velocity of a fluid close to it’s surface
◦ The two phenomenon important to NFETs
and molecular sensing are:
 Electrophoresis: motion of particles induced by an
electric field
 Electroosmosis: motion of the bulk fluid due to an
electric field
3 Different types of NFETs

Plain Dielectric Surface
◦ Our model advances the science by being the
first to consider the effect of Stern
Capacitance on channel dynamics

Soft Layer of Charge-Regulated molecules
◦ Our model advances the science by being the
first to consider charge regulation in a NFET

Soft Layer of non-regulated molecules
◦ This model is accurate for certain types of
soft layer fabrication processes
Plain Dielectric Surface NFET

The electrical double layer consist of:
◦ Stern Layer: Immobile counter-ion layer
(typically 1 ionic diameter thickness)
◦ Diffuse Layer: Higher concentration of
counter-ions to satisfy electroneutrality
(thickness of a debye length)
Previous studies of NFETs have ignored
the stern layer, due to the small thickness
 This assumption is not valid for all
conditions likely in a nanochannel

NFETS CONT’D
EDL : Electrical Double Layer
EOF : Electroosmotic Flow
Ez : Electric Field
; Vg : Gate Voltage
Circles Represent Published
Experimental Data
In both cases, a small capacitance fits
experimental data best
Zeta vs C0 for experimental data Gaudin and Fuerstenau
Zeta vs Vg for experimental data Oh et al
-60
100
2
Cs = 0.3 (F/m )
2
= 1 (F/m)
2
50
= 2 (F/m)
2
= 2.9 (F/m)
-80
 d (mV)
 d (mV)
0
-50
-100
2
Cs = 0.3 (F/m )
2
-100
= 1 (F/m)
2
= 2 (F/m)
2
= 2.9 (F/m)
-120
0
0.2
0.4
0.6
C0 (mM)
0.8
1
-45
-30
-15
0
V (V)
15
Verification of our Model
g
30
45
Low Salt Concentration
High Salt Concentration
Zeta vs pH for Vg = 5 V CKCl = 1 mM
Zeta vs pH for Vg = 5 V CKCl = 1 M
50
20
2
Cs = 0.3 F/(m )
2
0
Cs = 1 F/(m )
0
2
Cs = 2 F/(m )
-20
2
Cs = 2.9 F/(m )
2
Cs = 0.3 F/(m )
2
-50
Cs = 1 F/(m )
 d (mV)
 d (mV)
-40
-100
2
Cs = 2 F/(m )
2
Cs = 2.9 F/(m )
-60
-80
-150
-100
-200
-120
-250
2
3
4
5
6
7
pH
8
9
10
11
12
-140
2
3
4
5
6
7
pH
8
9
Affect on Zeta due to Cs
10
11
12
Low Salt Concentration
High Salt Concentration
Velocity vs X for pH = 8 Vg = 5 V CKCl = 1 mM
Velocity vs X for pH = 8 Vg = 5 V CKCl = 1 M
2000
1200
1800
1000
1600
2
Cs = 0.3 F/(m )
2
Cs = 1 F/(m )
1400
2
Cs = 2 F/(m )
800
2
Cs = 2.9 F/(m )
1000
U (m/s)
U (m/s)
1200
Cs = 0.3 F/(m2)
2
800
600
Cs = 1 F/(m )
2
400
Cs = 2 F/(m )
600
2
Cs = 2.9 F/(m )
400
200
200
0
0
5
10
15
X (nm)
20
25
30
0
0
0.5
1
1.5
2
X (nm)
2.5
3
3.5
Affect on Velocity due to Cs
4
The Gated, Charge-Regulated/Charge-Fixed
Nano Channel
Dielectric Layer
Soft Layer
Bulk Salt Solution
Gate Potential
Analytical Methods

COMSOL
Soft Layer
Bulk Layer
Trans side
Pore
Wafer
Cis side
1st Generation Model
2nd Generation Model
Interesting Results
Comparisons between Fixed and
Charge Regulated Nano Channels
Zeta vs. Vg
Maximum Velocity vs. Vg
0.2
0.002
0.15
0.0015
0.001
0.05
Charge Regulated
0
-50
0
50
Fixed Charge
Max Velocity
Zeta Potential
0.1
Charge Regulated
0.0005
Fixed Charge
-0.05
0
-50
-0.1
0
-0.0005
-0.15
-0.2
Vg
-0.001 Vg
50
The Gated, Charge-Regulated Nanopore



Gate Electrode with the soft layer is a unique study
Experimental data for Soft layer model exists
Soft layer adds complexity to fabrication
Fabrication

ALD
RF
Sputtering


FIB (focused Ion Beam)
Fabrication of the Nanopore
Walkthrough
Problems with current technology
Scientists and engineers have already
made considerable contributions to
developing nanopore based molecular
sensors
 Two major issues remain:

◦ The Capture rate is too low
 The DNA must be threaded through the pore
◦ The Translocation rate is too high
 When the DNA reaches the pore, it passes through
too quickly (1bp/μs)
Solving Translocation Speed

Two Forces are
responsible for the
DNA Translocation
◦ Electrophoretic Force
◦ Hydrodynamic Force
Electric forces
become strongest
inside Pore
 NFET can reduce
total force on
particle, thus tuning
translocation speed

Solving Capture Rate

By adding a gate to the
outer membrane surface,
we theorize that can use
the electric field to
hydro-dynamically coax
the particles toward the
pore
Conclusion / Moving Forward
We have already generated our results
from the one dimensional nanochannel
models
 We will simulate the velocity response in
a nanopore due to adding NFETs to the
channel and upstream (cis) wall of the
membrane.
 Our hope is too show that the cis
electrode can significantly improve the
capture rate

Gantt Chart
Questions?