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S.Carrara, EPFL Lausanne
(Switzerland)1
Sandro Carrara
Integrated System Laboratory – EPFL, Lausanne (Switzerland)
NanoNano--BioBio--Sensing Summer School Lausanne, JuSensing Summer School Lausanne, July 1st, 2009ly 1st, 2009
NanoNano--structures structures
Enhanced BioEnhanced Bio--sensingsensing
((Electrochemical SensorsElectrochemical Sensors))
S.Carrara, EPFL Lausanne
(Switzerland)2
What is Nanotechnology?What is Nanotechnology?
““Biology is not simply writing Biology is not simply writing
information; it is doing something information; it is doing something
about it. A biological system can about it. A biological system can
be exceedingly small. Many of be exceedingly small. Many of
the cells are very tiny, but they the cells are very tiny, but they
are very activeare very active””R.P.FeynmanR.P.Feynman
PlentyPlenty of Room at the of Room at the bottombottom, MIT , MIT lessonlesson, , DecDec. 1959. 1959
BioBio--inspired, so: inspired, so:
NanoNano--BIOBIO--technologytechnology
S.Carrara, EPFL Lausanne
(Switzerland)3
The MotivationThe Motivation
� 50 $ (machinery)
� 0.05 $ the single strip
� 100.000 $ (machinery)
� 1.000 $ the single µ-array
for DNAfor DNA
for Glucosefor Glucose
S.Carrara, EPFL Lausanne
(Switzerland)4
The MotivationThe Motivation
� 0.08 $/mm the single on-board CMOS bio-chip22
for DNAfor DNA
S.Carrara, EPFL Lausanne
(Switzerland)5
Point-of-Care in Personalized Therapy
New systems for Drugs Monitoring in personalized therapies are an important frontier challenge
S.Carrara, EPFL Lausanne
(Switzerland)6
Which are the building blocks?Which are the building blocks?
““the science of the science of objectsobjects withwith
smallestsmallest dimensionsdimensions rangingranging
fromfrom a few nanometers a few nanometers toto lessless
thanthan 100 nanometers100 nanometers””
G.M.WithesidesG.M.Withesides
SmallSmall 1(2005) 1721(2005) 172--179179
S.Carrara, EPFL Lausanne
(Switzerland)7
Building Building blocksblocks under 100 under 100 nmnm sizesize
WhitesidesWhitesides definitiondefinition!!
S.Carrara, EPFL Lausanne
(Switzerland)8
The proteins size
1.7 nm1.7 nm
3.8 nm3.8 nm
2.8 nm2.8 nm
Cytochrome P450Cytochrome P450
14.8nm14.8nm
12.8nm12.8nm
9.3 nm9.3 nm
HIV antibodyHIV antibody
8.2 nm8.2 nm
4.6 nm4.6 nm
Lactate OxidaseLactate Oxidase
S.Carrara, EPFL Lausanne
(Switzerland)9
How nano?How nano?
The dimension drives the phenomenaThe dimension drives the phenomena
zz→→nmnm
zz→→nmnm
yy→→nmnm
zz→→nmnm
yy→→nmnm
xx→→nmnm
1D: Quantum wells1D: Quantum wells
2D: Quantum wires2D: Quantum wires
3D: Quantum dots3D: Quantum dots
Molecular MonoMolecular Mono--
MultiMulti--layerslayers
Carbon NanotubesCarbon Nanotubes
Metallic and semiconductingMetallic and semiconducting
NanoparticlesNanoparticles
S.Carrara, EPFL Lausanne
(Switzerland)10
How nano?How nano?
The dimension drives the phenomenaThe dimension drives the phenomena
1D nano regions: Quantum well1D nano regions: Quantum well
2D nano region: Quantum wire2D nano region: Quantum wire
3D nano regions: Quantum dots3D nano regions: Quantum dots
polymerpolymer’’s layers + Carbon Nanotubess layers + Carbon Nanotubes
ProteinProtein’’s layers + metallic nanoparticless layers + metallic nanoparticles
Arachidate layers + semiArachidate layers + semi--conducting nanoparticlesconducting nanoparticles
S.Carrara, EPFL Lausanne
(Switzerland)11
Examples of NanoExamples of Nano--BioBio--sensing?sensing?
� DNA biosensors enhanced by 1D
nanostructures.
� Enzymes biosensors enhanced by 2D
nanostructures.
� Enzymes biosensors enhanced by 3D
nanostructures.
S.Carrara, EPFL Lausanne
(Switzerland)12
11--D Nanostructures for DNA D Nanostructures for DNA
detectiondetection
� Surface Wettability
� Surface Electrical Properties
S.Carrara, EPFL Lausanne
(Switzerland)13
Electrochemical InterfaceElectrochemical Interface
Ion planes are formed at the interface when
electrodes immersed in solution are polarized
AVERAGE IONS POSITION
S.Carrara, EPFL Lausanne
(Switzerland)14
Electrochemical InterfaceElectrochemical Interface
Ion planes are formed at the interface when
electrodes immersed in solution are polarized
New IONS POSITION
Previous IONS POSITION
IONS DISPLACEMENT
S.Carrara, EPFL Lausanne
(Switzerland)15
The DNA Detection PrincipleE
LE
CT
RO
DE
Rct
Cdl
RS
EL
EC
TR
OD
E
Applied voltage
(e.g. V<0)
Ionsdisplacement
DNA molecules
Cd
A∝
Unlabeled Unlabeled ssDNAssDNA may be detected withmay be detected with capacitance capacitance
measurements as due to charge displacementmeasurements as due to charge displacement
S.Carrara, EPFL Lausanne
(Switzerland)16
Method for a precise Capacitance measurementMethod for a precise Capacitance measurement
fCVI
I stepdc
AVG +=2
THE CAPACITANCE !THE CAPACITANCE !
)()( tiIti Cdc +=
∫+=2/
0
)(1
2
T
Cdc
AVG dttiT
II
Frequency!Frequency!
Current Based Capacitance Current Based Capacitance
Measurement (CBCM)Measurement (CBCM)
S.Carrara, EPFL Lausanne
(Switzerland)17
Liquid Measurement setLiquid Measurement set--upup
Chip is glued on a PCB
Bonding wiresOutput PCB pads
Fluidic cell
Two different Chambers 1mmX1mm
S.Carrara, EPFL Lausanne
(Switzerland)18
Large time driftLarge time drift
The problem of time instabilityThe problem of time instability
Capacitance variation during DNA hybridizationCapacitance variation during DNA hybridization
S.Carrara, EPFL Lausanne
(Switzerland)19
Detection of DNA sequences by using peptide nucleic acid as
probe molecules immobilized on Silicon with silane linkers
Large time driftLarge time drift
The problem of time instabilityThe problem of time instability
S.Carrara, EPFL Lausanne
(Switzerland)20
The problem of The problem of
largely scattered data pointslargely scattered data points
Large Standard deviationLarge Standard deviation
Capacitance variation during DNA hybridizationCapacitance variation during DNA hybridization
S.Carrara, EPFL Lausanne
(Switzerland)21
The Average Capacitance Drift in timeThe Average Capacitance Drift in time
Results in a too large standard deviations on the DNA detectionResults in a too large standard deviations on the DNA detection
Large Standard deviationLarge Standard deviation3 3 σσσσσσσσ: no detection with a : no detection with a
confidence level up to 99.7%confidence level up to 99.7% WhyWhy??
The problem of large errors in detectionThe problem of large errors in detection
S.Carrara, EPFL Lausanne
(Switzerland)22
The average capacitance upon the frequencies may shows us The average capacitance upon the frequencies may shows us
the DNA interface layer behaviorthe DNA interface layer behavior
0
100
200
300
400
500
600
0.01 0.1 1 10 100
Frequency [KHz]
Cap
acit
an
ce [
pF
] .
Targets and probes hybridized onto Gold electrodes
How to understand the reason How to understand the reason
of the time instability?of the time instability?
@ 1KHz@ 1KHz
Charge transfer pathways through the DNA layer affect the ideal Charge transfer pathways through the DNA layer affect the ideal
Capacitance behavior of the layer at interface with the solutionCapacitance behavior of the layer at interface with the solution samplesample
S.Carrara, EPFL Lausanne
(Switzerland)23
Charge transfer pathways Charge transfer pathways
through the probe layerthrough the probe layer
The frequency and time dependence of the Average Capacitance The frequency and time dependence of the Average Capacitance
are similar to those observed on clean electrodesare similar to those observed on clean electrodes
Ions transport through nanometer size layer apertures
S.Carrara, EPFL Lausanne
(Switzerland)24
CoCo--immobilized Thiols as Pathway Blockersimmobilized Thiols as Pathway Blockers
Repelling molecules may be used to improve the interfaceRepelling molecules may be used to improve the interface
behavior of Hybridized DNA monobehavior of Hybridized DNA mono--layerslayers
No layer apertures of direct access of the bare gold
MercaptoMercapto--HexanolHexanol
S.Carrara, EPFL Lausanne
(Switzerland)25
Improved insulating behaviorImproved insulating behavior
Redox reaction of K3Fe(CN)6 on gold electrode (a),
ss-DNA onto gold (b) and ss-DNA + 1-dodecanethiol onto gold (c)
Not enough Insulating
S.Carrara, EPFL Lausanne
(Switzerland)26
Further Thiols as Pathway BlockersFurther Thiols as Pathway Blockers
Other repelling molecules may be used to improve the interfaceOther repelling molecules may be used to improve the interface
Behavior of Hybridized DNA monoBehavior of Hybridized DNA mono--layerslayers
No layer apertures of direct access of the bare gold
MercaptoMercapto--HexanolHexanol
LipaLipa--DEA moleculeDEA molecule
S.Carrara, EPFL Lausanne
(Switzerland)27
N,NN,N--bis(2bis(2--hydroxyethyl)hydroxyethyl)--αα--lipoamide (lipoamide (LipaLipa--DEA)DEA) may be used as more efficient blocking agents
LipaLipa--DEA blockersDEA blockers
Different kind of thiols developed by Inger Different kind of thiols developed by Inger VikholmVikholm
S.Carrara, EPFL Lausanne
(Switzerland)28
Monolayer of ssDNA with blocking agents still
present deep groves crossing the film
13 nm
0.7 nm
200nm
Lipa-DEA
400nm
Mercapto-Hexanol
3,9 nm
ssDNAssDNA MonoMono--layers with layers with
blocking agentsblocking agents
S.Carrara, EPFL Lausanne
(Switzerland)29
Increased stability by using Increased stability by using LipaLipa--DEA as blocking agentDEA as blocking agent
Improved Capacitance StabilityImproved Capacitance Stability
Mercapto-Hexanol
Lipa-DEA
S.Carrara, EPFL Lausanne
(Switzerland)30
Improved surface for capacitance detectionImproved surface for capacitance detection
Highly packed thiols monolayer may be used Highly packed thiols monolayer may be used
to improve the DNA detection capabilityto improve the DNA detection capability
No ways of direct access of the bare gold
CovalentCovalent
bindingbinding Well formed Well formed
SAMSAM
S.Carrara, EPFL Lausanne
(Switzerland)31
Covalently linked by using EthyleneCovalently linked by using Ethylene--Glycol Glycol carboxyl terminated alkyl Thiolscarboxyl terminated alkyl Thiols
EthyleneEthylene--Glycol BlockersGlycol Blockers
ToTo preventprevent nonnon--specificspecific bindingbinding
Different kind of thiols developed by Different kind of thiols developed by G.M.WhitesidesG.M.Whitesides
Just entered the market in 2006Just entered the market in 2006
S.Carrara, EPFL Lausanne
(Switzerland)32
EthyleneEthylene--glycol Monoglycol Mono--layerslayers
Monolayer of alkanethiols with ethylene-glycol chains
does not present deep groves crossing the film
Non-EG
EG
3.75 nm
0.5 nm
S.Carrara, EPFL Lausanne
(Switzerland)33
Increased stability by using EthyleneIncreased stability by using Ethylene--Glycol thiolsGlycol thiols
Improved Capacitance StabilityImproved Capacitance StabilityThiols without glycole segment
0
50
100
150
200
250
300
350
400
450
500
0 2 4 6 8 10 12
time [min]
cap
acit
an
ce[n
F]
.
87 nF87 nFThiols with glycol segment
0
10
20
30
40
50
60
70
0 2 4 6 8 10
time [min]
Cap
acit
an
ce [
nF
] .
2 nF !2 nF !
non-EG
EG
S.Carrara, EPFL Lausanne
(Switzerland)34
Improved insulating behaviorImproved insulating behavior
Redox reaction of K3Fe(CN)6 on gold electrode (a),
non-EG-thiols film (b) and EG-thiols film (c)
Highly Insulating
S.Carrara, EPFL Lausanne
(Switzerland)35
Improved DNA arrayImproved DNA array
Capacitance vs frequency of NH2-terminated ss-DNA immobilized onto EG-Thiols precursor layer
Better Ideal capacitor behaviorBetter Ideal capacitor behavior
S.Carrara, EPFL Lausanne
(Switzerland)36
Why the EGWhy the EG--Thiols improve the Thiols improve the
capacitance detection?capacitance detection?
Large detection
errors reduction
DNA detection based on ss-DNA-SH terminated directly immobilized onto gold and ss-DNA-NH2 terminated immobilized onto EG-Thiols
S.Carrara, EPFL Lausanne
(Switzerland)37
Space filling of the EG thiols Space filling of the EG thiols
to close nanoto close nano--aperturesapertures
Space filling molecular model illustration of EG-thiols film presenting
a 1:1 mixture of -CON(CH2CH2O)nH (n ) 1, 3, or 6)
and O2H/CO2- groups.
Water molecules adsorptionWater molecules adsorption
S.Carrara, EPFL Lausanne
(Switzerland)38
Water Adsorption in thin filmsWater Adsorption in thin films
Film Water adsorption on alkyl thiol film chains
7 water molecules
S.Carrara, EPFL Lausanne
(Switzerland)39
Molecular conformations driven by terminal groups in EG-thiols
OH-terminated
Water Adsorption in thin filmsWater Adsorption in thin films
S.Carrara, EPFL Lausanne
(Switzerland)40
Water adsorption and Molecular conformation
in EG-thiols Film
Water Adsorption in thin filmsWater Adsorption in thin films
S.Carrara, EPFL Lausanne
(Switzerland)41
Covalently linked by using threeCovalently linked by using three--glycol glycol
carboxyl terminated alkyl Thiolscarboxyl terminated alkyl Thiols
OH-terminated
for probes binding
Water Adsorption in thin filmsWater Adsorption in thin films
helical conformation helical conformation
S.Carrara, EPFL Lausanne
(Switzerland)42
QCM measurements on dried EG-thiols film conditioned with water buffer
Water Adsorption in thin filmsWater Adsorption in thin films
S.Carrara, EPFL Lausanne
(Switzerland)43
Examples of NanoExamples of Nano--BioBio--sensing?sensing?
� Antibodies and DNA biosensors enhanced
by 1D nanostructures.
� Enzymes biosensors enhanced by 2D
nanostructures.
� Enzymes biosensors enhanced by 3D
nanostructures.
S.Carrara, EPFL Lausanne
(Switzerland)44
22--D Nanostructures for D Nanostructures for
Enzymes bioEnzymes bio--sensingsensing
� Surface Polarization
� Surface charging
� Electron Transfer Efficiency
S.Carrara, EPFL Lausanne
(Switzerland)45
Different kind of CNTs present different characteristics ranging from Metallic to
Semiconducting conductivity based on its chirality of the walls
What a CNT is?What a CNT is?
Courtesy: K. Banerjee/California Univ.
S.Carrara, EPFL Lausanne
(Switzerland)46
Electron Transfer Mediated by Electron Transfer Mediated by
2D nanostructures2D nanostructures
Carbon Nanotubes may be used in Electrochemical Interfaces
S.Carrara, EPFL Lausanne
(Switzerland)47
Redox reactions from VoltammetryRedox reactions from Voltammetry
( )( )
−=
tC
tC
nF
RTEE
O
R
,0
,0ln0
II
VV
Oxidation peakOxidation peakOxidation peakOxidation peakOxidation peakOxidation peakOxidation peakOxidation peak
Peak currentPeak currentPeak currentPeak currentPeak currentPeak currentPeak currentPeak current
Reduction peakReduction peakReduction peakReduction peakReduction peakReduction peakReduction peakReduction peak Reduction PotentialReduction PotentialReduction PotentialReduction PotentialReduction PotentialReduction PotentialReduction PotentialReduction Potential
Oxidation PotentialOxidation PotentialOxidation PotentialOxidation PotentialOxidation PotentialOxidation PotentialOxidation PotentialOxidation Potential
Standard PotentialStandard PotentialStandard PotentialStandard PotentialStandard PotentialStandard PotentialStandard PotentialStandard Potential
Nernst equationNernst equation
),0(),0(
2/1
tCRT
DnFnFADti
∝
νRandles-Sevcik equation
S.Carrara, EPFL - Lausanne
(Switzerland)48
Redox reactions from Redox reactions from AmperometryAmperometry
I
t
[C1]
[2C1]
[3C1]
V=Vo
2
2 ),(),(
x
txCD
t
txC
∂
∂=
∂
∂
∞→=
=
=
∞→
ttC
CtxC
CxC
o
x
o
,0),0(
),(
)0,(
lim
Linear diffusion equation
Boundary conditions
Cottrell equation
2/12/1
2/1 ),(),(
t
txCnFADtxi
π=
I
C(x,t)
Linear relationship
S.Carrara, EPFL - Lausanne
(Switzerland)49
Carbon Nanotubes contribute Carbon Nanotubes contribute
to Redox Reactions Efficiencyto Redox Reactions Efficiency
Cottrell equation
( )( )
−=
tC
tC
nF
RTEE
O
R
,0
,0ln0
2/12/1
2/1 ),(),(
t
txCnFADtxi
π=
Randles-Sevcik equation
Nernst equation
),0(),0(
2/1
tCRT
DnFnFADti
∝
ν
S.Carrara, EPFL Lausanne
(Switzerland)50
The peak potential is shifted toward lower potentials in case
of electrons-transfer is mediated by carbon nanotubes
Nernst Effect on Electrochemical H2O2
detection with Nano-structured Electrodes
S.Carrara, EPFL - Lausanne
(Switzerland)51
Carbon nanotubes contributions to Carbon nanotubes contributions to
Surface Concentration and LayeringSurface Concentration and Layering
( )( )
−=
tC
tC
nF
RTEE
O
R
,0
,0ln0
Nernst equation
-Zi
Zr
RS
CDL
RL Wr
CPE
fo
S.Carrara, EPFL Lausanne
(Switzerland)52
PolyPoly--((orthoortho))--anisidineanisidine (POAS)(POAS)
Nyquist impedance diagram of a POAS film. Experimental data
are showed by boxes. Data are acquired in the frequency range
from 100 mHz up to 1KHz. The solid line shows the best fitting
0
1000
2000
3000
4000
5000
6000
0 2000 4000 6000
Z'(ohm)
-Z"(
oh
m)
polyaniline derivatives have not the tendency to form well
organized films, as it was shown by AFM microscopy
Ram M.K., et al., Synthetic Metals 100(1999) 249-259
S.Carrara, EPFL Lausanne
(Switzerland)53
0
500
1000
1500
2000
2500
3000
3500
4000
0 1000 2000 3000 4000
Z'(ohm)
-Z"(
oh
m)
Nyquist impedance diagram of a POAS film. Experimental data are showed by
boxes. Data are acquired in the frequency range from 1KHz down to 100mHz.
The solid line shows the best fitting
Charge transfer resistance
coherently decreases with
the Lundberg Theory of
conducting mixtures
Conducting Polymer +Conducting Polymer + Carbon ParticlesCarbon Particles
S.Carrara, EPFL Lausanne
(Switzerland)54
0
50
100
150
200
250
300
350
400
0 100 200 300 400
Z'(ohm)
-Z"(
oh
m)
� Nyquist impedance diagrams of a POAS film synthesized with Carbon Nanotubes.
Experimental data are showed by boxes. Data are acquired in the frequency range
from 1KHz down to 100 mHz. The solid line shows the best fitting
Conducting Polymer + Multi Walled Conducting Polymer + Multi Walled CNTsCNTs
Pure electrostatic attraction
in the double layer and
faradic reaction are
responsible for the super-
capacitance phenomena in
Carbon Nanotube
structures
S.Carrara, EPFL Lausanne
(Switzerland)55
0
5
10
15
20
25
0 1 2 3 4 5
[H2O2] (mM)
Cu
rren
t (µ
A)
Bare electrode
Nanostructured electrode
sensitivity = 51.9 µA/mM cm2
sensitivity = 0.7 µA/mM cm2
~ 75 times more!!!!~ 75 times more!!!!
Cottrel Effects on H2O2 detection with Nano-
structured Electrodes
S.Carrara, EPFL Lausanne
(Switzerland)56
Peroxide DetectionPeroxide Detection
The peroxide detection is highly improved
by using carbon nanotubes
2 order of magnitude!!!
S.Carrara, EPFL Lausanne
(Switzerland)57
R-OH
P450 for Drugs MonitoringP450 for Drugs Monitoring
RH (e.g. benzphetaminebenzphetamine )
H-O-H
NADPH+H+
NADP+
Cytochrome
P450 2B4
Oxidized formmore soluble
then
faster secreted
O2
From electrode
Drugs detection !
2e -
3.6 nm3.6 nm
5.2 nm5.2 nm
4.9 nm4.9 nm
S.Carrara, EPFL - Lausanne
(Switzerland)58
BZ BZ
TK
EE
B
F
e
Ef−
+
=
1
1)(
φ
)(Ef
φφ
)(EfLUMO LUMO
G
==
h2
2
0
ennGG
e - e -
P1P2>P1
Electron Transfer Enhancer
An improved P450/Electrode coupling An improved P450/Electrode coupling
by Ballistic Nanotubesby Ballistic Nanotubes
S.Carrara, EPFL Lausanne
(Switzerland)59
Shift in Peak PotentialShift in Peak PotentialE
Nernst EffectNernst Effect
A shift in the Peak Potential is observed when the P450 Activity is mediated by Single Walled Carbon Nanotubes
S.Carrara, EPFL Lausanne
(Switzerland)60
Layering affects total ChargingLayering affects total Charging
Different Total Charges as calculated from Cyclic Voltammetry with electrodes not structured and structured
by using SW or MW Carbon Nanotubes
S.Carrara, EPFL Lausanne
(Switzerland)61
The Peak Current is larger when the P450 Activity is mediated The Peak Current is larger when the P450 Activity is mediated
by Multi Walled Carbon Nanotubesby Multi Walled Carbon Nanotubes
Peak current enhancementPeak current enhancement
RandlesRandles EffectEffect
S.Carrara, EPFL Lausanne
(Switzerland)62
Cottrell EffectCottrell Effect
Electron Transfer Electron Transfer
EnhancementEnhancement
The Sensitivity is enhanced when the P450 Activity is mediated The Sensitivity is enhanced when the P450 Activity is mediated
by Multi Walled Carbon Nanotubesby Multi Walled Carbon Nanotubes
S.Carrara, EPFL Lausanne
(Switzerland)63
OxidaseOxidase
OxygenOxygenProductProduct
Oxidases based detection: Oxidases based detection:
the working principlethe working principle
Oxygen peroxideOxygen peroxide
2e2e--AmperometricAmperometric
Detection !!!!!Detection !!!!!
Glucose, or Lactate, or Glutamate, or Glucose, or Lactate, or Glutamate, or ……
S.Carrara, EPFL Lausanne
(Switzerland)64
Sensitivity Enhancement in Glucose detection by using GOD
immobilized onto Multi Walled Carbon Nanotubes
Glucose detection by Oxidase and CNTGlucose detection by Oxidase and CNT
S.Carrara, EPFL Lausanne
(Switzerland)65
Sensitivity Enhancement in Lactate detection by using LOD
immobilized onto Multi Walled Carbon Nanotubes
Sensitivity enhancementSensitivity enhancement
Lactate detection by Oxidase and CNTLactate detection by Oxidase and CNT
S.Carrara, EPFL Lausanne
(Switzerland)66
Examples of NanoExamples of Nano--BioBio--sensing?sensing?
� Antibodies and DNA biosensors enhanced
by 1D nanostructures.
� Enzymes biosensors enhanced by 2D
nanostructures.
� Enzymes biosensors enhanced by 3D
nanostructures.
S.Carrara, EPFL Lausanne
(Switzerland)67
33--D Nanostructures for D Nanostructures for
Enzymes bioEnzymes bio--sensingsensing
� Single Electron Trapping
� Electron Transfer Efficiency
S.Carrara, EPFL Lausanne
(Switzerland)68
The CdS nanoparticle formationArachidic Acid
Cd
The final particle is surrounded by a insulating barrier The final particle is surrounded by a insulating barrier
also in case of other formation techniques!also in case of other formation techniques!
Semiconducting particles fabrication in Semiconducting particles fabrication in
Thin Solid FilmsThin Solid Films
S.Carrara, EPFL Lausanne
(Switzerland)69
Sulfide based NanoSulfide based Nano--particlesparticles
Mass variation during the grown of CdS nanoparticles in H2S atmosphere
0
5
10
15
20
25
0 5 10 15 20 25 30 35 40 45 50
tempo [minuti]
Massa c
om
ple
ssiv
a
delle n
an
op
art
icelle [
ng
]
S.Carrara, EPFL Lausanne
(Switzerland)70
They act as electron-traps
Tunneling barrier
Potential hole for the
charge carriersTrapped electron
The Two Barriers SystemsThe Two Barriers Systems
S.Carrara, EPFL Lausanne
(Switzerland)71
CdS nanoparticles (close to 5 nm in size) in Arachidic matrix
STM imaging and spectroscopy on STM imaging and spectroscopy on
nanoparticlesnanoparticles
Negative Differential Resistance (NDR) regionsNegative Differential Resistance (NDR) regions !!!!!!
Coulomb Coulomb StaircaseStaircase!!
Just a Just a tunnelingtunneling!!
S.Carrara, EPFL Lausanne
(Switzerland)72
A semi-classical theory
SingleSingle--electron conductivityelectron conductivity
mediated by a nanoparticlemediated by a nanoparticle
S.Carrara, EPFL Lausanne
(Switzerland)73
Bias Voltage [V]
0
2
4
6
8
10
12
0 0.5 1
Bias Voltage [V]
0
2
4
6
8
10
12
0 0.5 1
Bias Volta ge [V]
0
5
10
15
20
25
30
35
0 0.5 1
Bias Voltage [V]
0
2
4
6
8
10
12
0 0.5 1
SingleSingle--electron conductivity on electron conductivity on
single nanoparticlesingle nanoparticle
LikharevLikharev TheoryTheory
LimitLimit (1983)(1983)
More evident NDR when n increaseMore evident NDR when n increase
new Theorynew Theory
LimitLimit (1996)(1996)
The size drives the phenomena !!!The size drives the phenomena !!!
S.Carrara, EPFL Lausanne
(Switzerland)74
Metallic particles fabrication in solutionMetallic particles fabrication in solution
A A gold nuggetgold nugget is formed!is formed!
S.Carrara, EPFL Lausanne
(Switzerland)75
The thiols shell prevents further aggregations The thiols shell prevents further aggregations
and this allows monoand this allows mono--disperse nanoparticles!disperse nanoparticles!
Metallic particles fabrication in solutionMetallic particles fabrication in solution
S.Carrara, EPFL Lausanne
(Switzerland)76
TEM provides the metallic core size
while SAXS provides the organic coating size
Transmission Electron MicroscopyTransmission Electron Microscopy
5 nm5 nm
Small Angle XSmall Angle X--ray Scattering (SAXS)ray Scattering (SAXS)
9 nm9 nm
S.Carrara, EPFL Lausanne
(Switzerland)77
radius by TEM Radius by SAXS= 3.1 nm4.4 nm
Gold Nanoparticles SizeGold Nanoparticles Size
S.Carrara, EPFL Lausanne
(Switzerland)78
Conducting coreInsulating layer
Gold nanoparticles as Quantum DotsGold nanoparticles as Quantum Dots
This nanoThis nano--system is very useful system is very useful
for quantum effects !!!for quantum effects !!!
Potential hole for Potential hole for
charge carrierscharge carriers Tunneling barrierTunneling barrier
2 nm2 nm22 22
S.Carrara, EPFL - Lausanne
(Switzerland)79
BZ BZ
TK
EE
B
F
e
Ef−
+
=
1
1)(
φ
)(Ef
φφ
)(EfLUMO LUMO
e -
P1
P2>P1
Electron Transfer Enhancer
e -
An improved P450/Electrode An improved P450/Electrode
coupling by Quantum Dotscoupling by Quantum Dots
S.Carrara, EPFL Lausanne
(Switzerland)80
P450+Riboflavin+phospholipids+Albumine+
Glutaraldehyde
only NPs !only NPs !
Cottrell EffectCottrell Effect
Electron Transfer Electron Transfer
EnhancementEnhancement
The Sensitivity is enhanced when the P450 Activity is mediated The Sensitivity is enhanced when the P450 Activity is mediated
by gold nanoby gold nano--particlesparticles
S.Carrara, EPFL - Lausanne
(Switzerland)81
Nano affects Detection Nano affects Detection
Sensitivity and LimitSensitivity and Limit
Sensitivity
Detection Limit
S.Carrara, EPFL Lausanne
(Switzerland)82
Sensitivity Sensitivity vsvs Detection limitDetection limit
The case of Glucose
Nano!
S.Carrara, EPFL Lausanne
(Switzerland)83
Sensitivity Sensitivity vsvs Detection limitDetection limit
The case of lactate
Nano!
S.Carrara, EPFL Lausanne
(Switzerland)84
Sensitivity Sensitivity vsvs Detection limitDetection limit
The case of Hydrogen Peroxide
Nano!
S.Carrara, EPFL Lausanne
(Switzerland)85
Sensitivity Sensitivity vsvs Detection limitDetection limit
The case of Cholesterol
Nano!
S.Carrara, EPFL Lausanne
(Switzerland)86
“Nano” Improves Bio-Sensing
Conclusions (1)Conclusions (1)
11--5 nm5 nm
22--10 nm10 nm
2 nm2 nm
S.Carrara, EPFL Lausanne
(Switzerland)87
Conclusions (2)Conclusions (2)� 1D-nanostructures made by ethylene-glycol layers highly
improve insulating property of electrochemical interfaces
� 1D-nanostructures made by ethylene-glycol mono-layers highly improve DNA label-free detection
� 2D-nanostructures by carbon nanotubes improve charging effect and electron-transfer in electrochemical interfaces
� 2D-nanostructures by carbon nanotubes improve sensitivity and detection limit in enzymes based bio-sensing
� 3D-nanostructures by metallic or semiconducting particles assure single-electron trapping
� 3D-nanostructures by metallic particles improve sensitivity and detection limit in enzymes based bio-sensing
� Nanotechnology is useful
not only for Nanobamafabrication!!!
S.Carrara, EPFL Lausanne
(Switzerland)88
CoordinatesSandro Carrara Ph.D
EPFL - Swiss Federal Institute of Technology
in Lausanne
Web: http://si2.epfl.ch/~scarrara/
email: [email protected]
Dedicated to Janos Fendler, a great pioneer in the field of Nano-particle technology
Thanks to all the peoples helping me Thanks to all the peoples helping me
on this research and thank to all of on this research and thank to all of
you for your kindly attention!you for your kindly attention!