ionic transport through nanopores: from living cells to ionic diodes and transistors
DESCRIPTION
Ionic Transport Through Nanopores: From Living Cells to Ionic Diodes and Transistors. Zuzanna S. Siwy Department of Physics and Astronomy University of California, Irvine. Main Object of Our Studies. Our main object of studies is a single nanopore in a polymer film. -. +. 12 m m. - PowerPoint PPT PresentationTRANSCRIPT
Ionic Transport Through Nanopores: Ionic Transport Through Nanopores: From Living Cells to Ionic Diodes From Living Cells to Ionic Diodes
and Transistorsand Transistors
Zuzanna S. SiwyDepartment of Physics and Astronomy
University of California, Irvine
Our main object of studies is a single nanopore in a polymer film
We study ionic transport through single conical nanopores
+ -
Main Object of Our Studies
Several nanometers, typically 2-6 nm ~ 1 m
12 m
OutlineOutline
1. Motivation for studies of single nanopores
2. Fabrication of single nanopores by the track-etching technique.
3. Motivation for studying conically shaped nanopores.
4. Preparation of ionic devices controlling transport of ions in water solutions:
Preparation of ionic unipolar rectifiers.
Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices.
On the way to make a field effect transistor for ions.
Ionic diodes as biosensors.
5. Nanoprecipitation in nanopores and electrochemical oscillations.
6. Conclusions.
heavy ion
polymer foil
Impermeable lipid bilayer membrane
Membrane-Bound Transport Proteins
Allow for highly selective transport of ions, sugars, amino acids, etc. across the lipid bilayer membrane
Lessons from NatureLessons from Nature Transport Proteins are Nature’s Nanotubes Transport Proteins are Nature’s Nanotubes
Biological Pores are Smart “Holes” – Very Selective Biological Pores are Smart “Holes” – Very Selective Transport of Millions of Ions per 1 sTransport of Millions of Ions per 1 s
Potassium selective channel with four K+ in the selectivity filter (right panel).
R. MacKinnon, P. Agre 2003
< 1 nm
E. Gouaux, R. MacKinnon, Science 310, 1461 (2005).S. Berneche, B.Roux, Nature 414, 73 (2001).
A potassium selective channel is a very important player in the nerve signaling.
W. Nonner, D. Gillespie, D. Henderson, B. Eisenberg, J. Phys. Chem. 105, 6427 (2001);
E.W. McCleskey, J. Gen. Physiol. 113, 765 (1999)
[Ca2+] << [Na+] Ca2+ and Na+ have basically the same diameter.
Selectivity of L-Type Calcium Channels Selectivity of L-Type Calcium Channels (Heart Muscle Regulation)(Heart Muscle Regulation)
Negative groups COO-
Preparation of the Simplest Calcium Channel/PorePreparation of the Simplest Calcium Channel/PorePHYSICS approach
Gillespie, D., Boda, D., He Y. Apel, P., Siwy, Z.S. (2008) Synthetic Nanopores as a Test Case for Ion Channel Theories: The Anomalous Mole Fraction Effect. Biophysical Journal 95, 609-619.
Our synthetic analogue (a synthetic hole) is indeed Ca2+ selective!
Theoretical predictions: highly charged lining of the pore and small pore volume lead to Ca2+ selectivity.
COO-
COO- COO- COO- COO-
COO- COO- COO- COO-
~1 e/nm2
~1 e/nm2
e = electron charge
COO- = carboxyl group with charge -e
Diode - Like Characteristics of Biological ChannelsDiode - Like Characteristics of Biological Channels
I [pA]
V [mV]
T. Baukrowitz et al. EMBO 18, 847 (1999)Y. Jiang et al. Nature 417, 515 (2002)
Many biological channels are switches for ions
What are the Physical Requirements for Making Ionic Diodes and Transistors? Perhaps a Basis for Ionic Electronics?
PHYSICS approach
A diode perfectly rectifies currents so that it flows in one direction
rectifier
diode
Nanopores – Studying Interactions at the NanoscaleNanopores – Studying Interactions at the Nanoscale
+ + + + + + + + + +
+ + + + + + + + +
_ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _
Nanopores give a unique possibility to control transport of ions and charged molecules in water-based solutions.
Nanopores have very large surface!
Nanopores as Basis for BiosensorsNanopores as Basis for Biosensors
Sub-femtoliter volume!
Very few molecules actually fit there!
Basis for single molecule detection!
• Preparation of various components of IONIC CIRCUITS for ions and molecules in a water solution: urgent need for systems that operate in water.
• For that we need: TEMPLATE - robust single nanopores with tunable geometry and surface chemistry i.e. tunable electrochemical potential.
I Will Talk About..I Will Talk About..
OutlineOutline
heavy ion
polymer foil
1. Motivation for studies of single nanopores.
2. Fabrication of single nanopores by the track-etching technique.
3. Motivation for studying conically shaped nanopores.
4. Preparation of ionic devices controlling transport of ions in water solutions:
Preparation of ionic unipolar rectifiers.
Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices.
On the way to make a field effect transistor for ions.
Ionic diodes as biosensors.
5. Nanoprecipitation in nanopores and electrochemical oscillations.
6. Conclusions.
1. Irradiation with e.g. Xe, Au, U
(~2.2 GeV i.e. ~ 15% c)
2. Chemical etching
Linear accelerator UNILAC, GSI
Darmstadt, Germany
E. Loriot
1 ion 1 latent track 1 pore !
Heavy Ions as a Working ToolHeavy Ions as a Working Tool
Latent tracks
R.L. Fleischer, P.B. Price, R.M. Walker (1975)
1. Irradiation with e.g. Xe, Au, U
(~2.2 GeV i.e. ~ 15% c)
2. Chemical etching
Linear accelerator UNILAC, GSI
Darmstadt, Germany
E. Loriot
1 ion 1 latent track 1 pore !
Heavy Ions as a Working ToolHeavy Ions as a Working Tool
R.L. Fleischer, P.B. Price, R.M. Walker (1975)
Tuning the Pore Shape during EtchingTuning the Pore Shape during Etching
Vb
Vt
Vb – Rate of non-specific etching the so-called bulk etching
Vt - Rate of etching along the latent track
Recipes for cylindrical and conical nanopores:
Cylindrical pores: high Vt and low Vb; for PET 0.5 M NaOH in 70 ºCConical pores: low Vt and high Vb; for PET 9 M NaOH, RT
Why Do We Want to Work with Asymmetric Pores?Why Do We Want to Work with Asymmetric Pores?
Cylindrical pore Tapered cone
d d
D
21
4
d
LR
dD
LR
4
2
L
>>
d=1 nm results in current of 3.9 pA. d=1 nm, D=2 m, results in current of ~740 pA.
Example for 0.5 V, 1 M KCl, L = 10m
I
U
NaOH acidic solution
242 244 246 248 250 2520
50
100
150
200
curr
ent
(pA
)
time (min)
Cu
rren
t (p
A)
time (min)
Conical Pores are Obtained by Putting Etch Solution on One Side of Membrane and Stop Solution of the Other
Z. Siwy et al. Nucl. Instr. Meth. B 208, 143-148 (2003); Applied Physics A 76, 781-785; Surface Science 532-535, 1061-1066 (2003).
Single ion irradiation
Gold Replica of a Single Conical PoreGold Replica of a Single Conical Pore
P. Scopece et al. Nanotechnology 17, 3951 (2006)~ 2 – 10 nm
Etch solution
9 M NaOH
CathodeAnode
For polyethylene terephthalate
Electro-Stopping Technique to Prepare Double-Conical Pores
Etch solution
9 M NaOH
P. Apel, Dubna
Cross – Section of Membranes with Double-Conical Nanopores
Hydrolysis of Ester Bonds with NaOH in PET Causes Formation of COOH Groups
OH-
The surface density of COOH groups was estimated to be ~ 1.0 per nm2
_ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _
OutlineOutline
heavy ion
polymer foil
1. Motivation for studies of single nanopores
2. Fabrication of single nanopores by the track-etching technique.
3. Motivation for studying conically shaped nanopores.
4. Preparation of ionic devices controlling transport of ions in water solutions:
Preparation of ionic unipolar rectifiers.
Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices.
On the way to make a field effect transistor for ions.
Ionic diodes as biosensors.
5. Nanoprecipitation in nanopores and electrochemical oscillations.
6. Conclusions.
Transport Properties of Conical NanoporesTransport Properties of Conical Nanopores
I
U
0.1 M KCl 0.1 M KCl
Z. Siwy et al. Europhys. Lett. 60, 349 (2002); Z. Siwy et al. Surface Science 532-535, 1061 (2003)
Single Conical Nanopores Rectify Ion CurrentSingle Conical Nanopores Rectify Ion Current
-1000 -500 500 1000
-0.6
-0.3
0.3
0.6Current (nA)
Voltage (mV)
VtVb
Vb - Vt
~ 3 nm ~ 600 nm
0.1 M KCl, pH 8
0.1 M KCl, pH 3
COO-
_ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _ _ _
COOH
t+ ~ 0.80PET and Kapton pores are selective for positive ions (cations)
I
U
Which Ions Are Transported?Which Ions Are Transported?
Z. Siwy, A Fulinski, Phys. Rev. Lett. 89, 198103 (2002); Am. J. Phys. 72, 567 (2004).Siwy Z., Adv. Funct. Mat.16, 735 (2006).
UNIPOLAR DEVICE – mainly pass through
_ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _
Why do Asymmetric and Charged Pores RectifyWhy do Asymmetric and Charged Pores Rectify
Siwy Z., Fulinski A. Phys. Rev. Lett. 89, 198103 (2002); Siwy Z., Fulinski A. The American Journal of Physics 74 (2004) 567; Siwy Z., Adv. Funct. Mat.16, 735 (2006).
The profile of electric potential V(z) of a cation in an asymmetric nanopore
z
Cervera, J., Schiedt, B., Ramirez, P. Europhys. Lett. 71, 35-41 (2005).
PROBLEM: Degree of Rectification of Conical PROBLEM: Degree of Rectification of Conical NanoporesNanopores
U (V)
I (nA)1
-2
-4
UI
UIfrec
10recf
-3 3
Ideally, from application stand point one wants a SWITCH i.e. basically zero leakage current.
How to Make an Ionic Switch?How to Make an Ionic Switch?
H. Daiguji, P. Yang, A. Majumdar, NanoLett., 4, 137 (2005).
I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)
+ + + + + + + + + +
+ + + + + + + + +
_ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _
Depletion zone
+ + + + + + + + + +
+ + + + + + + + +
_ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _
HIGH Conductance State of NanoporeHIGH Conductance State of Nanopore
BIPOLAR DEVICE – current carried by both
Eric Kalman
Targeted Modification of the TipTargeted Modification of the Tip
GOAL!
,
The negative groups (COO-) at the narrow opening have to be changed into groups with positive charges, e.g. NH3
+
Ethylenediamine+ EDC
Succinide anhydride + EDC
Ethylenediamine+ EDC
Succinide anhydride + EDC
Steady-State Solution of Diffusion ProblemSteady-State Solution of Diffusion Problem
100 200 300 400 5000.0
0.2
0.4
0.6
0.8
1.0
c (
x)
x [nm]
Distribution of concentration of a reagent introduced only on the tip side of the membrane
C0 CL=0
Targeted modification of
the tip
1)( 0 x
L
A
acxc
Only the region of the pore close to the tip with high enough EDC and amines concentration will be modified!
x
Modification ChemistryModification Chemistry
Ethylene diamine + EDC, 0.1 M KCl, pH 5.5
Ethylenediamine + EDC
Succinide anhydride + EDC
_ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _
_ _
0.1 M KCl, pH 5.5
-5 -4 -3 -2 -1 0 1 2 3 4 5
0
2
4
6
8
10
12C
urr
ent
(nA
)
Voltage (V)
217)5(
)5(
VI
VI
An Ionic Diode Made From a Nanopore An Ionic Diode Made From a Nanopore with a Positive Tipwith a Positive Tip
I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)
0.1 M KCl, pH 5.5
Positively Charged NanoporePositively Charged Nanopore
-5 -4 -3 -2 -1 0 1 2 3 4 5-2
0
2
4
6
8
10
12
Cu
rren
t (n
A)
Voltage (V)
+
+ + + + + + + + +
+ + + + + + + +
7)5(
)5(
VI
VI
0.1 M KCl, pH 5.5
61)5(
)5(
VI
VI
-5 -4 -3 -2 -1 0 1 2 3 4 5-12
-10
-8
-6
-4
-2
0
Cu
rren
t (n
A)
Voltage (V)
I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)
0.1 M KCl, pH 5.5
An Ionic Diode Made From a Nanopore An Ionic Diode Made From a Nanopore with a Negative Tipwith a Negative Tip
Tuning RectificationTuning Rectification
We can measure ion rectification degree in situ during the modification!
I. Vlassiouk, Z.S. Siwy, Nano Lett. 7, 553 (2007)
Miedema, H.; Vrouenraets, M.; Wierenga, J.; Meijberg, W.; Robillard, G.; Eisenberg, B. A Biological Porin Engineered into a Molecular, Nanofluidic Diode. Nano Letters 7 (2007) 2886-2891.
Diode Pattern Realized in a Bacterial BioporeDiode Pattern Realized in a Bacterial Biopore
WITHOUTcharges
WITH charges
Unipolar Diodes Were Also PreparedUnipolar Diodes Were Also Prepared
R. Karnik, C. Duan, K. Castelino, H. Daiguji, A. Majumdar Nano Letters 7, 547-551 (2007). I. Vlassiouk, S. Smirnov, Z. Siwy, ACS Nano 2, 1589 (2008)
Voltage (V)
10 mM KCl
Poisson-Nernst-Planck Modeling of Ionic DiodesPoisson-Nernst-Planck Modeling of Ionic Diodes
+
++
++
+
_ _ _
_ _ _
+
++
++
+
_ _ _
_ _ _
)(
)(
Tk
eCzCDJ
CCe
B
iiiii
o
Ci – concentration of positive and negative ions - electric potential - dielectric constantJi – flux of an ion i with charge zi
Density of charge carriers is described by the Boltzmann statistics
480 500 5200.0
0.1
0.2
0.3
0.4
0.5
Co
nce
ntr
atio
n, M
x, nm
K+ Cl-
480 500 520
-0.02
0.00
0.02
0.04
Vo
ltag
e,
V
x, nm
Voltage
+
++
++
+
_ _ _
_ _ _
+
++
++
+
_ _ _
_ _ _
A Semiconductor Diode Vs an Ionic DiodeA Semiconductor Diode Vs an Ionic DiodeC
arrie
r co
ncen
trat
ion
p-doped n-doped
electrons (-)holes (+)
Voltage
1 m long, 0.5 e/nm2, 0.1 M KCl
Numerical solutions of PNP
doping
eNN
VNN
lad
d
a
pn
2
0
1
,
1-D Analytical Approximations for Diodes1-D Analytical Approximations for Diodes
0Va
ldep
+
++
++
+
_ _ _
_ _ _
+
++
++
+
_ _ _
_ _ _
a – pore radius - surface charge density
Depletion zone
I. Vlassiouk, S. Smirnov, Z. Siwy, ACS Nano 2, 1589 (2008)
2
2
2 oB
BPopen VV
L
CDe
Tk
eaI
L
CaDeI bulkBP
closed
2322
Current
Voltage
N.W. Ashcroft, N.D. Mermin, Solid State Physics, Thomas Learning, 1976
1Tk
eV
gene
genhopen
BeIII
Current
Voltage
gene
genhclosed III
+ + + + + + + + + +
+ + + + + + + + +
_ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _
Depletion zone
Depletion Zone in LONG PoresDepletion Zone in LONG Pores
I. Vlassiouk, S. Smirnov, ACS Nano 2, 1589 (2008)
Depletion Zone in SHORT PoresDepletion Zone in SHORT Pores
+ + + + + + + + + +
+ + + + + + + + +
_ _ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _
The depletion zone fills the whole pore, which can be treated as a neutral pore
I. Vlassiouk, S. Smirnov, ACS Nano 2, 1589 (2008)
Opening of Short DiodesOpening of Short Diodes
Cbulk = 0.1 M KCl, charge density 0.5 e/nm2, radius 4 nm
4 2 0 -2 -44 2 0 -2 -420
0
-20
-40
0
-20
-40
UP diode charged reservoirs
D
Bias (V)
L=2nm L=4nm L=6nm L=10nm L=25nm
B
UP diodeneutral reservoirs
I (n
A)
Bias (V)
L=2nm L=4nm L=6nm L=10nm L=25nm
A
BP diode neutral reservoirs
I (n
A)
L=2nm L=4nm L= 8nm L=10nm L=12nm L=16nm
C
BP diode charged reservoirs
L=2nm L=4nm L=8nm L=10nm L=12nm L=16nm
(V)
Preparation of Ionic Bipolar Junction: TransistorPreparation of Ionic Bipolar Junction: Transistor
+ + + + +
+ + + + +
+
+
+ + + + + +
+ + + + + +
Cl- K+ Cl-
P. Apel, Dubna
I
V
diode P-N junctions
+ _ _ _ _ _ _
_ _ _ _ _ _
+ +
+ + +
0.1 M KCl 0.1 M KCl
_ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _
-4 -2 0 2 4-1200
-800
-400
0
Cu
rren
t (p
A)
Voltage (V)
-4 -2 0 2 4
-400
-200
0
200
400
Cu
rren
t (p
A)
Voltage (V)
0.1 M KCl 0.1 M KCl
+ _ _ _
_ _ _ _
+ +
+ + +
+ + +
+ +
0.1 M KCl 0.1 M KCl
-4 -2 0 2 4
-20
-10
0
10
20C
urr
en
t (p
A)
Voltage (V)
(a)
(b)
(c)
+ _ _ _ _ _ _
_ _ _ _ _ _
+ +
+ + +
0.1 M KCl 0.1 M KCl
_ _ _ _ _ _ _ _ _
_ _ _ _ _ _ _ _ _
-4 -2 0 2 4-1200
-800
-400
0
Cu
rren
t (p
A)
Voltage (V)
-4 -2 0 2 4
-400
-200
0
200
400
Cu
rren
t (p
A)
Voltage (V)
0.1 M KCl 0.1 M KCl
+ _ _ _
_ _ _ _
+ +
+ + +
+ + +
+ +
0.1 M KCl 0.1 M KCl
-4 -2 0 2 4
-20
-10
0
10
20C
urr
en
t (p
A)
Voltage (V)
(a)
(b)
(c)
Step-by-Step ModificationsStep-by-Step Modifications
E. Kalman, I. Vlassiouk, Z. Siwy, Advanced Materials 20, 293 (2008).
-4 -2 0 2 4
-200
-100
0
100
200
0.5 M 0.25 M 0.1 M
Cu
rren
t (p
A)
Voltage (V)
Performance of Ionic BJTPerformance of Ionic BJT
Salt concentration determines the potential in the pore and thus the leakage current level in BJT
+ _ _ _
_ _ _ _
+ +
+ + +
+ + +
+ +
0.5 M KCl 0.5 M KCl
Performance of Ionic BJT – pH responsePerformance of Ionic BJT – pH response
-4 -2 0 2 4-60
-40
-20
0
20
40
60
pH 8.0 pH 7.0C
urr
ent
(pA
)
Voltage (V)
“+ - +” junction
-4 -2 0 2 4-200
-100
0
100
200
pH 5.4 pH 6.0 pH 7.0 pH 8.0 pH 9.0
Cu
rre
nt
(pA
)
Voltage (V)
+ + + + +
+ + + + +
+
+
+ + + + + +
+ + + + + +
p n p
+ + + + +
+ + + + +
+
+
+ + + + + +
+ + + + + +
p n p
“0 - 0”
“0 - 0”junction“0 - 0”junction
+ + + + +
+ + + + +
+
+
+ + + + + +
+ + + + + +
+ + + + +
+ + + + +
+
+
+ + + + + +
+ + + + + +
“+ 0 +” junction
E. Kalman, I. Vlassiouk, Z. Siwy, Advanced Materials 20, 293 (2008).
Ionic Gated Channel with Electrically Addressable Ionic Gated Channel with Electrically Addressable Gate – On the Way to Make FETGate – On the Way to Make FET
12 m PET
Membrane
Not to scale
Au Gate Electrode
SiO2 Insulating Layer
Ti Adhesion Layers
Positive Bias
Current Input
0.1 M KCl
Keithley 6487Picoammeter
Tektronix AFG320Function Generator
Ground
Gate Electrode
_ +Voltage
Out_ In+
Voltage Current
Faraday Cage
0.1 M KCl
Positive Bias
Current Input
0.1 M KCl
Keithley 6487Picoammeter
Tektronix AFG320Function Generator
Ground
Gate Electrode
_ +Voltage
Out_ In+
Voltage Current
Faraday Cage
0.1 M KCl
-1.0 -0.5 0.5 1.0
-4
4
8
12
16
Air 0V- 0.2V -0.4V -0.6V -0.8V -1.0V
Current (nA)
Voltage Um (V)
Gated Conical NanoporeGated Conical Nanopore
Applying negative gate voltage to the gate causes suppression of ion currents
0 V
-1.0 V
Gated Conical NanoporeGated Conical Nanopore
--------
-
---
+
+
+
- - - - - - ---
--
-
+
+
+-
Negatively Charged Carboxyl Groups
-
-
+
-
-
+++
+ -
-
+
+
_
-
Concentration depletion induced by a gate electrode
Silica layer
Gold layerBias
voltage
- --
- -
-
+
---
+ + +
+
++
--
-
-------
-+
-+
+ - +
-
+-
-
+
-
+
+
-
+
-
+
+
+
+ +
----
-----
--
---
- -
+
+
Active exclusion
zone50nm
50nm-
--
-
------
10nm
+
+
+
Negatively Charged Silanol Groups
--
----------------
--
------
++
++
++
-- -- -- -- -- -- ------
----
--
++
++
++--
Negatively Charged Carboxyl Groups
--
--
++
--
--
++++++
++ --
--
++
++
__
--
Concentration depletion induced by a gate electrode
Silica layer
Gold layerBias
voltage
-- ----
-- --
--
++
------
++ ++ ++
++
++++
--
-
-------
-+
-+
+ - +
-
+-
-
+
-
+
+
-
+
-
+
+
+
+ +
----
-----
--
---
- -
+
+
----
--
--------------
--++
--++
++ -- ++
--
++--
--
++
--
++
++
--
++
--
++
++
++
++ ++
--------
----------
----
------
-- --
++
++
Active exclusion
zone50nm
50nm--
----
--
------------
10nm
++
++
++
Negatively Charged Silanol Groups
-- Negatively Charged Silanol Groups
---
E. Kalman, O. Sudre, I. Vlassiouk, Z. Siwy, Analytical and Bioanalytical Chemistry 394, 413 (2009)
1. Motivation for studies of single nanopores
2. Fabrication of single nanopores by the track-etching technique.
3. Motivation for studying conically shaped nanopores.
4. Preparation of ionic devices controlling transport of ions in water solutions:
Preparation of ionic unipolar rectifiers.
Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices.
On the way to make a field effect transistor for ions.
Ionic Diodes as Biosensors
5. Nanoprecipitation in nanopores and electrochemical oscillations.
6. Conclusions.
OutlineOutline
Summary: Tuning Current-Voltage Curves Of Summary: Tuning Current-Voltage Curves Of Nanopores by the Surface ChargeNanopores by the Surface Charge
I
I I
U
U U
Surface charge patterns Corresponding current-voltage curvesAND
Changes of the surface pattern are induced upon binding of an analyte
I Vlassiouk, T, Kozel, Z.S. Siwy, JACS 131, 8211-8220.
Prototype of the Sensor for Avidin and StreptavidinPrototype of the Sensor for Avidin and Streptavidin
+Avidin(+)
__
__
_ __
__
__
__
_ __
__
biotin
+ +
+
Current Current
VoltageVoltage
KCl as the background electrolyte
Prototype of the Sensor for AvidinPrototype of the Sensor for Avidin
-6 -4 -2 2 4 6
-6
-4
-2
2
4
6
8
Tip modified with biotin Avidin on top
Voltage (V)
Current (nA)
Nanopore with the tip modified with biotin;10 mM KCl, pH 7.0
With avidin0.5 M, 2 h
With biotin
I
U
10 mM KCl 10 mM KCl
I
U
10 mM KClavidin
10 mM KClavidin
II
U
10 mM KCl 10 mM KCl
II
U
10 mM KClavidin
10 mM KClavidin
Prototype of the Sensor for StreptavidinPrototype of the Sensor for Streptavidin
4 5 6 7 8
1
2
3
4
pH
pI
+ Streptavidin, pI ~ 6
_+
pH < 6 pH > 6
-2 -1 1 2
-1.2
-0.8
-0.4
0.4
0.8Current (nA)
Voltage (V)
10 mM KCl
biotin
Rec
tifi
cati
on
deg
ree
I(+
2V)/
I(-2
)pH 8.0
pH 4.2
pH 5.8
__
__
_ __
__
__
__
_ __
__
GOALLabel-free sensor for antigens that are bioterrorism agents
Prototype: Monitoring infection with Bacillus anthracis
www.wikipedia.org
Capsule of poly--glutamic acid (DPGA)thus it is heavily negatively charged
Infection with Bacillus anthracis results in DFGA in the blood at the levels that are higher than 20 ng/ml (~10 pM DFGA).
Bacillus anthracis
Sensor for a Real “Stuff” – pI of the mAb for Sensor for a Real “Stuff” – pI of the mAb for DPGADPGA
-4 -2 2 4
-4
4
8
12
16
pH 4.8
pH 6.0
pH 8.0
_ _ _
_ _ _
+
++
_ _ _
_ _ _
0
00
_ _ _
_ _ _
_
_ _
pH < pI pH ~ pI pH > pI
Current (nA)
Voltage (V)
Monoclonal antibody for
polyglutamic acid Prof. T. Kozel, University of
Nevada(F2G26)
I Vlassiouk, T, Kozel, Z.S. Siwy, JACS 131, 8211-8220.
Sensing SignalSensing Signal
-4 -2 2 4
-4
4
8
12
16 pH 4.8
pH 6.0
Current (nA)
Voltage (V)
+ polyglutamic acid
-4 -2 2 4
-40
-30
-20
-10
Current (nA)
Voltage (V)
4 5 6 7 80.01
0.1
1
10
100
pH
Rec
tific
atio
n de
gree
I(+
5V)/
I(-5
)
Before adding DPGA
After adding DPGA
pH 8.0
pH 6.0
pH 4.8
pH 8.0
_ _ _
_ _ _
_ _ _
_ _ _ _ _ _
_ _ _
_ _ _
_ _ _
Monoclonal antibody for polyglutamic acid
1. Motivation for studies of single nanopores
2. Fabrication of single nanopores by the track-etching technique.
3. Motivation for studying conically shaped nanopores.
4. Preparation of ionic devices controlling transport of ions in water solutions:
Preparation of ionic unipolar rectifiers.
Preparation of an ionic bipolar diode and transistor (BJT); similarities and differences to semiconductor devices.
On the way to make a field effect transistor for ions.
Ionic Diodes as Biosensors.
5. Nanoprecipitation in nanopores and electrochemical oscillations.
6. Conclusions.
OutlineOutline
I
U
0.1 M KCl + Ca2+
0.1 M KCl + Ca2+
Conductivity Cell Used for Recording Conductivity Cell Used for Recording Current-Voltage CurvesCurrent-Voltage Curves
[Ca2+] << [K+] or
[Mg2+] << [K+] or
[Co2+] << [K+]
_
Mg(OH)2
[Mg2+] [OH-]2 <Ksp=5.6 10-12
[Mg2+] [OH-]2 >> Ksp
Precipitation in a NanoporePrecipitation in a Nanopore
0.1 M KCl – background electrolyte
A ‘plug’ can be created inside a nanopore!!
• Ionic concentrations inside a nanopore depend on the surface charge and applied voltage
•Concentration of cations in a negatively charged pore can be much higher than in the bulk.
-1000 -500 0 500 1000-2000
-1500
-1000
-500
0
500
Cu
rren
t (p
A)
Voltage (mV)
-2000
-1000
0
20 s
Cu
rren
t (p
A)
-200
-100
0
40 s
Cu
rren
t (p
A)
KCl
0.5 mM Mg2+
5.0 mM Mg2+
50 M Mg2+
A
A B
B
Evidence for the Precipitation, Evidence for the Precipitation, Mg(OH)Mg(OH)22
Mg(OH)2 Ksp = 5.61·10-12
M. Powell et al. Nature Nanotechn. 3, 51 (2008)
Modeling by the Poisson-Nernst-Planck EquationsModeling by the Poisson-Nernst-Planck Equations
Products of ionic activities at -1 Vare above the solubility product for Mg(OH)2
Products of ionic activities at +1 Vare below the solubility product
Modeling by the Poisson-Nernst-Planck EquationsModeling by the Poisson-Nernst-Planck Equations
Products of ionic activities are very strongly voltage-dependent!
-2 -1 0 1 2-4
-3
-2
-1
0
1
2
Voltage (V)
Cu
rren
t (n
A)
0.1 M KCl
0.1 M KCl + 0.1 mM CaCl2
0.1 M KCl + 0.4 mM CaCl2
0.1 M KCl + 0.7 mM CaCl2
Z. Siwy et al. Nano Lett. 6 (2006) 473-477.
Evidence for the Precipitation (I) CaHPOEvidence for the Precipitation (I) CaHPO44
pH 8, 2 mM PBS
Pore opening 5 nm
CaHPO4 Ksp 2 ·10-7
Cu
rren
t (p
A)
400 ms
-400
-200
0
Cu
rren
t (p
A)
400 ms
-400
-200
0
C
B
-600
-400
-200
0
10 s
Cu
rren
t (p
A)
A
-1000 -500 0 500 1000
-600
-400
-200
0
200
400
600C
urr
ent
(pA
)
Voltage (mV)
Cu
rren
t (p
A)
BC KCl
0.1 mM Ca2+
0.5 mM Ca2+
1.0 mM Ca2+
A
Evidence for the PrecipitationEvidence for the Precipitation
2 mM PBS
-1000 -500 0 500 1000
-600
-400
-200
0
200
400
Cu
rren
t (p
A)
Voltage (mV)
-800
-400
0
20 s
Cu
rren
t (p
A)
2 s-400
-200
0
Cu
rren
t (p
A)
1 s
-400
-200
0
D
EF
D
E
F
0.1 mM PBS
1.0 mM PBS
5.0 mM PBS
0.2 mM PBS
0.2 mM Ca2+
Evidence for the Precipitation (IIEvidence for the Precipitation (II),), CoHPO CoHPO44
-1.0 -0.5 0.0 0.5 1.0-1600
-1200
-800
-400
0
400
Cu
rren
t (p
A)
Voltage (V)
A
B
0.01 mM Co2+
0.10 mM Co2+
KCl
-600
-400
-200
0
20 s
4020Time (s)
IN 0
(pA
)
-400
-200
0
1 20 s
3632Time (s)
IN 0
(pA
)-400
-200
0
1
4 sC
urr
ent
(pA
)C
urr
ent
(pA
)C
urr
ent
(pA
)
CoHPO4 Ksp 1 ·10-7
M. Powell et al. Nature Nanotechn. 3, 51 (2008)
Singing of Divalent CationsSinging of Divalent Cations
4 02 00T im e (s )
IN 0
(pA
)
-4 0 0
0
2 3 41pA
20 s
0.1 M KCl + 0.1 mM Co2+
5 25 04 8T im e (s )
IN 0
(pA
)
-4 0 0
-2 0 0
0
24
pA
1 s
0.1 M KCl + 0.1 mM Ca2+
Co2+Ca2+
Application of the System with Calcium/Cobalt to Build Application of the System with Calcium/Cobalt to Build Stochastic Sensors?Stochastic Sensors?
Detecting Neomycin
Detecting SpermineDetecting Spermine
ConclusionsConclusions
We have a lot of fun doing research with nanopores!
1. Unipolar and Bipolar ionic diodes were prepared on the basis of conical nanopores with tailored surface chemistry.
2. The principle of operation of the bipolar diode is analogous to that of a bipolar semiconductor diode.
SIWY GROUPSIWY GROUP
Eric Kalman
Matt Powell
Dr. Dragos ConstantinAlumni
Dr. IvanVlassiouk
Gra
du
ate
stu
den
ts
Laura Inees – IM-SURE and UROP Fellow
Matt Davenport
Catherine SmithGael NguyenMike Chiang,
MCSB student
AcknowledgmentsAcknowledgments
UC Irvine• Prof. Clare Yu • Prof. Craig Martens • Prof. Reg Penner• Prof. Thorsten Ritz• Prof. Ken Shea
• Prof. Vicente Aguillella• Prof. Robert S. Eisenberg, Rush Medical College, Chicago• Gesellschaft fuer Schwerionenforschung (GSI), Darmstadt, Germany • Dr. Christina Trautmann, GSI, Germany• Dr. Olivier Sudre, Teledyne & Imaging, Thousand Oaks• Prof. S. Smirnov, New Mexico State University
A.P. Sloan FoundationRCE Pacific Southwest
ACS Petroleum Research FundInstitute for Complex Adaptive Matter
Institute for Surface and Interface Science
• TEMPO group (Prof. Steve White, Prof. Doug Tobias
• Prof. Thomas Kozel, University of Nevada