bm 519 nanotechnology in bio sensors and biosensor market

8/6/2019 BM 519 Nanotechnology in Bio Sensors and Biosensor Market

1/106

Nanotechnology in Biosensors

Nanowire Biosensors

Nanotube Biosensors

Nanoparticles

FET and CMOS devices


2/106

Nanotechnology (sometimes shortened to "nanotech") is the study of

manipulating matter on an atomic and molecular scale. Generally

nanotechnology deals with structures sized between 1 to 100 nanometer in at

least one dimension, and involves developing materials or devices within that

size. Quantum mechanical effects are very important at this scale.

Drexel University materials science graduate

student Jennifer S. Atchison made the silicon

nanocones shown in this scanning electron

microscope image by decomposing silane at

high temperature in a chemical vapor

deposition apparatus.


3/106

This transcript of the classic talk that Richard Feynman gave on December 29th 1959 at theannual meeting of the American Physical Society at the California Institute of Technology

(Caltech) was first published in the February 1960 issue of Caltech's Engineering and

Science.

Richard Feynman

Miniaturizing the computer

I don't know how to do this on a small scale in a

practical way, but I do know that computing

machines are very large; they fill rooms. Why can't

we make them very small, make them of little wires,

little elements---and by little, I mean little. For

instance, the wires should be 10 or 100 atoms in

diameter, and the circuits should be a few thousand

angstroms across.


4/106


5/106

What is nanostructure?

One dimention 1-100 nm

2-D Structures (1-D confinement)

Thin Films Planar Quantum wells Superlattices


2 m

Si Nanowire Array

Nanowires Quantum wires Nanorods Nanotubes


Nanoparticle Quantum Dots Multiwall Carbon

Nanotube


6/106


7/106

Bulk Material Large Nanoparticle Small Nanoparticle

Energy Levels in a Metal


8/106

Nanowires

Solid, 1D

Conductive, Semi-conductive, Insulator

Crystalline

Quantum Confinement Effect (electon, phonon)2 m

with increase in band gap

Thermal conductivity decreases with decreasing

nanowire diameter

Core-shell synthesis is possible

anow re rray

Si/SiGe Nanowires


9/106

Publications

Web of Science September 2007 data; 4699 publications

December 2010 data; 13186 publications


10/106

Nanowire Synthesis


11/106

Electron Beam Lithography

Molecular Beam Epitaxy (MBE)

Thermal Evaporation Laser-Ablation

Tem late Assisted S nthesis

Nanowire Synthesis

High Pressure Injection

Vapor Depostion

Electrodeposition


12/106

Template Above

Template Assisted Au catalyzed Si Nanowire Synthesis

100nm

1m

Au Nanoparticles


13/106

Chemical Vapor

Deposition(CVD)

Nat. Protocols 1, 1711-1724 (2006).


14/106

Si Nanowires

Basn (Tor)

30-70

Basn (Tor)

30-70

Scaklk

480-500 C

Zaman

10 saniye-25

dakika

Proses Gaz/Tayc Gas

75 25

50 50

25 75

SiH4/N2

Au Kolloid Boyutu

2-20 nm

Au Kolloid Deriimi

0.01-1

Scaklk

480-500 C

Zaman

10 saniye-25

dakika

Proses Gaz/Tayc Gas

75 25

50 50

25 75

SiH4/N2

Au Kolloid Boyutu

2-20 nm

Au Kolloid Deriimi

0.01-1


15/106

Nomenclature

CVD - Chemical Vapor Deposition MWNT - Multi-Walled Carbon Nanotubes

SWNT - Single-Walled Carbon Nanotubes

15

XRD - X-ray Diffraction Pyrolysis - decomposition of organic material through the

application of heat and the absence of oxygen

Chirality - measure of the twist of the nanotube

Ablation - Removing a surface material by vaporization


16/106

What Are Carbon Nanotubes?

CNT can be described as asheet of graphite rolled into a

cylinder

Constructed from hexagonal

16

rings of carbon Can have one layer or multiple

layers

Can have caps at the ends

making them look like pills

Information retrieved from: http://www.photon.t.u-tokyo.ac.jp/~maruyama/agallery/agallery.html


17/106

Nanotube Classification Chirality - twist of the

nanotube

Described as the vector

R (n, m)

Armchair vector, R vector,

17

angle = 0, armchair nanotube

0 < < 30, chiral nanotube

> 30, zigzag nanotube

Information and image retrieved from: http://www.pa.msu.edu/cmp/csc/ntproperties/


18/106

Nanotube Classification MWNT

Consist of 2 or more layers ofcarbon

Tend to form unordered clumps

SWNT

18

Consist of just one layer ofcarbon

Greater tendency to align into

ordered bundles

Used to test theory of nanotube

properties

Images retrieved from: http://www.photon.t.u-tokyo.ac.jp/~maruyama/agallery/agallery.html


19/106

Applications Electronic Devices

Nanotube TVs Nano-wiring

High Strength Composites

19

100 times as strong as steel and 1/6 the weight Conductive Composites

Medical Applications

Encase drug into nanotube capsule for morepredictable time release


20/106

Synthesis Techniques Nanotube Synthesis By CVD Process

Plasma Enhanced CVD Nanotube Synthesis

Nanotube Synthesis By Arc Discharge in a Magnetic Field

Carbon Nanotube Synthesis Using Laser Ablation of Metallic Catalyst

20

Web of Science December 2010 data; 27117 publications


21/106

Chemical Vapor Deposition1. Gas enters chamber at room

temperature (cooler than thereaction temperature)

2. Gas is heated as it approachesthe substrate

3. Gases then react with the

21

su strate or un ergo c em ca

reaction in the Reaction Zonebefore reacting with thesubstrate forming the depositedmaterial

4. Gaseous products are then

removed from the reactionchamber

Information and photo retrieved from:

http://www.sandia.gov/1100/CVDwww/cvdinfo.htm


22/106

Nanotube Synthesis By CVD Process

22Schematic from: Andrews, Jacques, Qian, and Rantell, Mulitwall Carbon Nanotubes: Synthesis and Application


23/106

Nanotube Synthesis By CVD Process

Source of carbon atoms usually comes from an

organic compound Mixed with a metal catalyst and inert gas

23

temperatures ranging from 600C to 1200C Pyrolysis of organic compound deposits

carbon (as soot) and carbon nanotubes onreactor wall (usually a tube constructed fromquartz)


24/106


25/106


26/106

Nanowire sensor approach

Approach for the direct electrical detection of

biological macromolecules uses semiconductingnanowires or carbon nanotubes configured as field-

effect transistors, which change conductance upon

binding of charged macromolecules to receptorslinked to the device surfaces

Carbon nanotubes on the electrode


27/106

Field effect transistor (FET).. An overview

The name transistor is a shortened version of the

original term, transfer resistor Relies on using one electrical signal to controlRelies on using one electrical signal to control

anotheranother

be altered by the input signal. This behaviour can be used to transfer patterns of

signal fluctuation from a small input signal to a

larger output signal.


28/106

Again Semiconductors

Group III-V single-crystal semiconductors are used

for detection of a target analyte. If changes are reversible and detectable by means of

cahnges in optical and/or electrical properties, on-line

detection is possible. Adsorbate can be categorized as donors (D) or

acceptors (A) and can react in the following way:

D D++e-

A+e-A-


29/106

Semiconductors

For silicon and germanium, the Fermi level is essentiallyhalfway between the valence and conduction bands.

No conduction occurs at 0 K, at higher temperatures a finitenumber of electrons can reach the conduction band and providesome current. In doped semiconductors, extra energy levels are

added.


30/106

Silicon Energy Bands

At finite temperatures, the number of electrons which reach the conduction band

and contribute to current can be modeled by the Fermi function. That current is

small compared to that in doped semiconductors under the same conditions.

The increase in conductivity with temperature can be modeled in terms of the

Fermi function, which allows one to calculate the population of the conduction

band.


31/106

P-Type Semiconductor

Lack of electrons results in

lowering fermi level down to

The addition of trivalent impurities such as boron,

aluminum or gallium to an intrinsic semiconductor creates

deficiencies of valence electrons, called "holes".


32/106

N-Type Semiconductor

Fermi level rises up toconduction band in

negative type semi conductor

The addition of pentavalent impurities such as antimony, arsenic

or phosphorous contributes free electrons, greatly increasing the

conductivity of the intrinsic semiconductor.


33/106

Bands for Doped Semiconductors

In n-type material there are electron energy levels near the top ofthe band gap so that they can be easily excited into theconduction band.

In p-type material, extra holes in the band gap allow excitationof valence band electrons, leaving mobile holes in the valenceband.


34/106

Semiconductor Current The electrons which have been freed from their lattice positions

into the conduction band can move through the material.

Holes are migrating across the material in the direction opposite

to the free electron movement.

This current is highly temperature dependent.

The current flow in a semiconductor is influenced by the density of energy

states which in turn influences the electron density in the conduction band.


35/106

P-N Junction coming closer to transistors

When p-type and n-type materials are placed in contact with each other, the junction

behaves very differently than either type of material alone.

Specifically, current will flow readily in one direction (forward biased) but not in the other

(reverse biased), creating the basic diode.

The open circles on the left side of the junction above represent "holes" or deficiencies of

electrons in the lattice which can act like positive charge carriers. The solid circles on the

right of the junction represent the available electrons from the n-type dopant.

Near the junction, electrons diffuse across to combine with holes, creating a "depletion

region".


36/106

Depletion Region

When a p-n junction is formed, some of the free electrons in the n-region

diffuse across the junction and combine with holes to form negative ions.

In so doing they leave behind positive ions at the donor impurity sites.


37/106

Depletion Region Details

In the p-type region there are holes from the acceptor

impurities and in the n-type region there are extra

electrons.

When a p-n junction is formed, some of the electrons from

the n-region which have reached the conduction band are

free to diffuse across the junction and combine with holes.

Filling a hole makes a negative ion and leaves behind a

positive ion on the n-side. A space charge builds up,

creating a depletion region which inhibits any further

electron transfer unless it is helped by putting a forward

bias on the junction.


38/106

Forward bias and Reverse bias An applied voltage in the forward direction as

indicated assists electrons in overcoming the

coulomb barrier of the space charge in depletion

region. Electrons will flow with very small

resistance in the forward direction.

An applied voltage with the indicated polarity further

impedes the flow of electrons across the junction. For

conduction in the device, electrons from the N region

must move to the junction and combine with holes in

the P region. A reverse voltage drives the electrons

away from the junction, preventing conduction.


39/106

Forward Biased Conduction

e orwar curren n a p-n

junction (forward-biased) involves

electrons from the n-type material

moving leftward across the

junction and combining with holes

in the p-type material.


40/106

Field effect transistor

A pair of metallic contacts are

placed at each end of the channel.

When we apply a voltage betweenthese, a current can flow along the

channel from one contact to the

other. The contact which launches

the source, the one that 'eats' themat the other end is called the drain.

In a sense, the device is a bit like

a PN-junction diode, except that

we've connected two wires to theN-type side.


41/106


42/106

1D SiNWs as field effect transistors Binding to the surface of a nanowire can

lead to depletion or accumulation of charge

carriers in the bulk of the 1D structure

(over nanowire).

Remember that in planar FET, charge

defficiency was only on the surface region

of the device.

This increase sensitivity (single molecule

detection possible)


43/106

Sensitivity Binding strength dependent on Fermi level

(equilibrium binding constant)

Binding strengthAnalyte detection sensitivity

(detection limit)

erm eve n or p- ype sem con uc or crys a

growth, impurities)

Amplification on FET structure binding properties

Sensitivity increment irreversibility on binding

Si Nanowire Field Effect Transistors (FET)


44/106


Nat. Protocols 1, 1711-1724 (2006).



45/106


Nat. Protocols 1, 1711-1724 (2006).



46/106


Nat. Protocols 1, 1711-1724 (2006).



47/106

Virus Detection

Influenza A

Adenovirus


Proc. Natl. Acad. Sci. USA 101, 14017-14022 (2004).

80 Attomolar (10-18

)

Appx. 50 Virus/mL



48/106

DNA SENSORS

60 Femtomolar PNA

100 HeLA Cells

( )

Nat. Biotechnol. 23, 1294-1301 (2005).


49/106

Carbon Nanotubes


50/106

Carbon Nanotubes

Carbon Nanotubes


51/106

Carbon Nanotubes


52/106

Carbon Nanotubes


53/106

Carbon Nanotubes


54/106


55/106

Carbon Nanotubes


56/106

NANOPARTICLES


57/106

NANOPARTICLES

Metalic Nanoparticles

(Au, Ag)

Quantum Dots

Polymeric Nanoparticles


58/106

Quantum Dots

3 nm


59/106

Quantum Dots


60/106

Quantum Dots

The most intriguing features of QDs is that the particle size determines many of the QD

properties most importantly the wavelength of fluorescence emission.

Individual quantum dots are too small to see

with the naked eye, but they signal their

presence by emitting light in a variety of

colors. They emit different colors depending

on their size.

Colloidal CdSe quantum dots dispersed in hexane

Quantum Dot Type


61/106

Core-shellcoating

CoreQuantum

c

Core type Qdot Core/shell type Qdot

Quantum Dot Type

Semiconductor nanocrystals can also be produced with other shapes such as;

CdSe Core Qdot

Cd

Se

CdSe/Zns Core/shell Qdot

S

Zn

Boomerangs

Tetrapods, or many other shapes

Pyramids

Rods

Spheres Biological application

Quantum Dots Structure


62/106

Core ShellThe first ste in s nthesizin dot

Q

Biomolecules(SA)Polymer coating

Inorganic shell (ZnS)

Nanocrystal

Core (CdSe)

Cadmium sulfide (CdS): UV-blue

Cadmium selenide (CdSe): the bulkof

the visible spectrum

Cadmium telluride (CdTe): the far red

and near-infrared

The core nanocrystal determines the

color

material of wider bandgap than the corematerial.

Stabilize the material,

Improve quantum yield (increases the

intensity of the fluorescence)

Reduce photo-degradation.

nanocrystals is the preparation of a core that

is composed of :

Optical Properties


63/106

Color Tunability

Tuning the QD emission wavelenght by changing theparticle size orcomposition

QDots are available in multiple emissions from465 nm (visible) to 2300 nm (infared)

Optical Properties

Quantum Dot CompositionQuantum Dot size

A

Optical Properties


64/106

Narrow Fluorescent Emission

Qdots exhibit narrow and symmetric emission peaks (FWHM typically 25-35 nm).

Broadband Absorption Source

QDots have a broader absorption profile compared to traditional organic dyes and phosphors.

p p

CdSe Quantum Dot

Wavelength (nm) Wavelength (nm)

FITC: Fluorescein isothiocyanate

(organic dye)

Simultaneous labeling and detection of multiple analytes

Optical Properties


65/106

p p

Em

issionWa

vel

All samples are induced to emit their respective

colors even though a single source was used to

excite them.

Emission Wavelength (nm)

Excitation 360 nm

This facilitates simultaneous detection, imaging and quantification

Vials of Quantum Dots in front of a common UV

hand lamp

Different size QDs can be excited with a simple excitation sources

Optical Properties


66/106

StabilityThe nanocrystal materials are very stable. They are composed of inert inorganic compounds

and are further stabilized with our engineered shells that resist photochemical damage.

Intensity

QDot nanocrystals fluoresce intensely and exhibit high quantum yields. Brightness is

comparable to or greater than traditional organic fluore dyes.

In vivo imaging of Xenopus embryos using time-lapse

microscopy

The same timefluoresce brightly for

much longer

organic-dye

quantum dots

The signal is seen to

fade in time

Optical Properties


67/106

Fluorescence Lifetimes

CdSe/ZnS nanocrystals have 15-20ns fluorescence lifetimes which is an order of magnitude

greater than conventional organic dyes and even greater than the auto-fluorescence lifetime of

organic dyes.

A

A: Nuclear antigen: QDot (red)

Microtubules: Alexa 488 (Green)

B: Nuclear antigen: Alexa 488 (Green)

Microtubules: QDot (red)

B

Synthesis of Quantum DotsSynthesis of Quantum Dots


68/106

Synthesis of Quantum DotsSynthesis of Quantum Dots

Vapor Deposition

Ion Implantation

Organometallic Synthesis via Pyrolysis

Sol-gel Method

Micelle Method


69/106



70/106

High-temperature Pyrolytic Reaction

Core/shell Type Qdot (CdSe/ZnS)

Coordinating solvent (TOPO,TOP, hexadecylamine)

High temperatures

Metallic or organometallic precursor Zinc,cadmium or mercury species

Chalcogen precursorSulfur, selenium or tellurium species



71/106

QDs obtained from these procedures are:

Highly fluorescent,

Photostable,

Sufficiently monodisperse for use as labels in biological studies, But they are not soluble in aqueous solution and biocompatible

Surface modification Bioconjugation

Surface Modification


72/106

Two general methods

A:Surface -exchange of hydrophobic

surfactant molecules for bifunctional

linker molecules

TOPO-coated QD replaced with

mercaptoacetic acid or silane

LIGAND EXCHANGE

B:Phase-transfer methods usingamphiphilic molecules that act as detergent

for solubilizing the QD coated with

hydrophobic groups.

TOPO ligands on the surface may be

interact with an amphiphilic polymer

(octylamine-modified polyacrylic acid).

HYDROPHOBIC INTERACTIONS

A

B

Bioconjugation Methods


73/106

a) Bifunctional linkage

b) Hydrophobic attraction

d) Electrostatic attraction

c) Silanizatione) Nanobeads

Two to five protein molecules

+

50 or more small molecules

(oligonucleotides or peptides)

conjugated to a single 4 nm QD

Biological Applications


74/106

Qdots Based Array


75/106

Barcoding technology

Code readout

FluorescenceInten

sity

The use of 6 colors and 10 intensity levels can encode 1

million protein or nucleic acid sequences

Polystyrene beads are embedded with multicolor

CdSe/ZnS QDs

Barcoding technology can be used for

gene profiling and high-throughput drug anddisease screening

Nature Biotechnology 19:631-635-97 (2001), Quantum-dot-tagged microbeads

for multiplexed optical coding of biomolecules

Wavelength

Qdots Based Array


76/106

Prepared multicolor QD-tagged beads, and conjugated these beads to biomoleculesto carry out biological assays

DesignedDesigned aa modelmodel DNADNA

hybridizationhybridization systemsystem usingusing

oligonucleotideoligonucleotide probesprobes andandtripletriple--colorcolor encodedencoded beadsbeads

DNA hybridization assays using QD-tagged beads. Probe oligos (No. 14) were

conjugated to the beads by crosslinking,

and target oligos (No. 14) were detected

with a blue fluorescent dye such as

Cascade Blue. After hybridization,

nonspecific molecules and excess reagents

were removed by washing

Qdots Based Array


77/106

EncodingEncoding

Application Format

Multiplex gene

expression

Multiplex SNPgenotyping

Encoded beads each with

gene-spesific oligo

Encoded beads with gene-

spesific oligos

Quantum dotscolors

Spectrally-encodedmixtures

Encoded beads, cells, etc.

Mix to formunique

mixtures(codes)

Polymer beads (oligos), variouscell types, or cells with diferrent

receptors

Multiplexed

immunoassays

Multiplexed cell-

based assays

Multiplexed reporter

assays

Encoded beads withantibodies

Mixed cell yypes encodedwith qdots

Encoded cell linesexpressing various

receptors

Quantum dotcolors

Qdots Based Array


78/106

Specific target

QD Nanoprobes Nanoassembly

UV Light

Excitation

Colocalization

Biological Threat Detection System Using QDs

NANOLETTERS 2005,Vol. 5, No. 9,1693-1697, Multiplexed Hybridization Detection with Multicolor Colocalization of Quantum Dot Nanoprobes.

Colocalization

Qdots Based Array


79/106

Simulated multiplexed analysis of anthrax-related genetic targets for pathogenicity

A IIIC

NANOLETTERS 2005,Vol. 5, No. 9,1693-1697, Multiplexed Hybridization Detection with Multicolor Colocalization of Quantum Dot Nanoprobes.

III IV

C: Fluorescent images I, II, III, and IV correlate with samples I, II, III, and IV,respectively.

A: Color pallet for the three pairs of target specific QD

nanoprobes and their resulting colocalized fluorescent

images upon sandwich hybridization.

B: Four samples containing different combinations of the three

targets rpoB, capC, and pagA. Checks represent the existence ofcertain target sequences. Sample IV does not contain any target and

is used as a negative control.


80/106




81/106

Gold (Au)Gold (Au)

Metalic nanoparticles possess optical properties that make them uniquely suitable forbiosensing applications.

Their optical properties strongly depend on both the particle size and shape and are related to

the interaction between the metal conduction electrons and the electric field component of the

incident electromagnetic radiation, which leads to strong, characteristic absorption bands in

the visible to infrared part of the spectrum.

In aqueous solutions, gold nanostructures exhibit strong plasmon bands depending on their

geometric shape and size.

LSPR (Localized Yzey Plasmon Resonans) nanosensors can be used as diagnosticLSPR (Localized Yzey Plasmon Resonans) nanosensors can be used as diagnostic

tools for a variety of diseasestools for a variety of diseases

Gold nanoparticles are particularly attractive for studies in a biological environment

because they show no surface oxidation

High biocompatibility without any surface modification.

In addition, thiol chemistry can be applied to conjugate molecules to the gold surface.

Size and Geometry Variation on Surface Plasmon

Absorption


82/106

Size change in Au spheres

has little effect on absorption

maximum position

Au nanorods have two

absor tion eaks. One is due to

plasmon setup along the

axial direction and the otherone is along the radial

direction

The longitudinal plasmonabsorption position changes with

aspect ratio.

Colloidal form of Gold Silver

particles for different shapes and


83/106

sizes

Au-Ag alloy

nanoparticles

Au nanorods

Ag nanoprisms

Optic Properties of Au and Ag Nanoparticles


84/106

Au nanospheresAu nanospheres Ag nanoparticlesAg nanoparticles

Ag nanoparticlesAg nanoparticles Ag nanoparticlesAg nanoparticles

Ag nanoparticlesAg nanoparticles Ag nanoparticlesAg nanoparticles

SPR (Surface Plasmon Resonance)


85/106

Modification of sensor surface

Au film

Glass slide

Probe immobilization

Injection of analyte solution

Binding

Changing of refraktive index or

dielectric constant

LSPR (Localized Surface Plasmon Resonance)


86/106

Silanization of glasssurface

mmobilization of Aunanoparticles on the glass

surface

The nanoparticles have tunable optical

properties, which make them an ideal LSPR-

sensing platform. By functionalizing the

nanoparticle surface with the appropriate

receptor, the LSPR nanosensor can be used todetect specific ligands

+

ens ng sur ace s expose o e arge

molecules

The refractive index of the surrounding

enviroment changes on binding to thereceptors, inducing a shift in the

nanoparticles LSPR,max . The

wavelength shift is monitored by UV-

Visible spectrocopy .

LSPR (Localized Surface Plasmon Resonance)


87/106

Nanosphere Lithography (NL)Nanosphere Lithography (NL)

LSPR Sandwich Assay

A ti ADDL tib d


88/106

Anti ADDL antibody

ADDL antibody

Ag nanoparticles after modificationwith anti- ADDL antibody

after exposure to ADDL antibody

And anti -ADDL antibody

Biomarker for Alzheimers diseaseBiomarker for Alzheimers disease

Synthesis of Gold NanoparticlesSynthesis of Gold Nanoparticles

S h i l ld t il il d d b th h i l d ti f ld lt


89/106

Chlorauric acidsolution (HAuCl4)

Spherical gold nanopartciles are easily produced by the chemical reduction of gold salts

Boil 15 min

NaBH4 solution

Bring to a boil 50 mL of 2.5Bring to a boil 50 mL of 2.51010--44 M chlorauric acid solutionM chlorauric acid solution

Add 0.16 to 1.0 mL of 34 mM sodium citrate solution to the boiling solution whileAdd 0.16 to 1.0 mL of 34 mM sodium citrate solution to the boiling solution while stirringstirring

After a minute will be faint blue and then darkening over 5 min to a brilliant redAfter a minute will be faint blue and then darkening over 5 min to a brilliant red

Synthesis of Au Nanorods

S d di t d th d


90/106

Seed-mediated growth procedure

I. Seeds are prepared by

reducing of a metal salt

with a strong reducing

agent (Na-citrate or

NaBH4)

II. The growth steps

involve the addition of

more metal salt to the

seed solution, with aweak reducing agent, in

the presence of a

surfactant

Capping agent: CTAB

Weak reducing agents:ascorbic acid

The nanorod growth reaction was terminated after 3 h by removing the reaction solution by centrifugation at

5000 rpm for 15 min. The nanorods were resuspensed in 0.005 M CTAB solutions and found to remain stable for

up to 100 days.

Bioconjugation MethodsBioconjugation Methods

ThiolThiol endend groupsgroups (( SH)SH) areare enoughenough toto covalentlycovalently bondbond thethe moleculesmolecules toto thethe goldgold surfacessurfaces ItIt isis


91/106

Au Nanoprobes

SH

SH

SH

SH

SH

+

(Merca toundeconic acid

ThiolThiol endend groupsgroups ((--SH)SH) areare enoughenough toto covalentlycovalently bondbond thethe moleculesmolecules toto thethe goldgold surfacessurfaces.. ItIt isisquitequite straightstraight forward,forward, easyeasy andand quickquick reaction,reaction, andand requiresrequires nono otherother chemicalschemicals.. ItIt isis possiblepossible toto

couplecouple moleculesmolecules carryingcarrying thiolthiol endend groupgroup onon goldgold surfacessurfaces simplysimply

Probe Molecules

Oligonucleotides

Oligopeptides/proteins Antibodies

(MUA))

TheThe alkylalkyl chainschains cancan bebe terminatedterminated byby reactivereactive headhead groups,groups, suchsuch asas carboxyliccarboxylic acidacid (COOH)(COOH) andandaminoamino groupsgroups (NH(NH22),), areare usedused forfor formationformation ofof funtionalizedfuntionalized SAMsSAMs.. TheseThese alkylalkyl chanischanis cancan bebe

covalentlycovalently bondbond toto goldgold surfacessurfaces toto actact asas spacerspacer armarm forfor furtherfurther immobilizationimmobilization stepssteps.. TheseThese

sublayerssublayers areare capablecapable ofof supportingsupporting thethe immobilizationimmobilization ofof biomoleculesbiomolecules viavia covalentcovalent chemicalchemical

couplingcoupling..

Multiplexing Ag Nanosensor CarbohydrateMultiplexing Ag Nanosensor Carbohydrate--SensingSensing

ChipChip


92/106

677 nm

682 nm

724.6 nm

724.5 nm

Ag nanobiosensor consisted of nanosphere

litography-fabricated Ag nanoparticles with

the same in plane width but two different out-

of-plane heights: 35 and 75 nm and thus twodifferent LSPR max.

(B) Ag nanoparticles (75 nm height) mannosemodification

Mannose

Galactose

Concavalin A

(C) Ag nanoparticles (75 nm height) afterexposure to Con A.

(D) Ag nanoparticles (35 nm height) galactosemodification

(C) Ag nanoparticles (35 nm height) afterexposure to Con A.

Multiplex Biosensor Using Gold Nanorods


93/106

Gold nanorod molecular probe

Gold nanorods (GNRs) with different aspect ratios

were fabricated through seed-mediated growth and

surface activation by alkanethiols for the attachment of

antibodies to yield gold nanorod molecular probes

(GNrMPs). Multiplexsensing was demonstrated by the distinct response of

the plasmon spectra of the GNrMPs to binding events

of three targets (goat anti-human IgG1 Fab, rabbit

antimouse IgG1 Fab, rabbit anti-sheep IgG (H+L))

Multiplex Biosensor Using Gold Nanorods


94/106

(a) (b)

Multiplexing detection of various targets using GNrMPs

(a) One target; (b) two targets; (c) three targets

(c)

Solution-phase Nanoparticles


95/106

2. Releasing the Ag nanoparticles into solution.

3.Asymmetrically linked solution-phase Ag

nanoparticles with alkanedithiol to form dimer.

Surface-bound Ag nanoparticles fabricated by nanospherelithograpy and modified with a SAM of alkanethiol.

Market For Biosensors


96/106

Need for Biosensor

Diagnostic Market Di ti t l d ll t bli h d


97/106

Diagnostic Market. Diagnostics represent a very large and well established

market that is continually expanding. Particularly in the current climate of

prevention rather than remedy, the need for detection at increasingly lower

limits is increasing in many diverse areas. Estimates of the market size and

future projections tend to be difficult and inaccurate.

Need for Biosensor


98/106

Clinical Testing. However, undoubtedly clinical testing iis one of the biggest

diagnostic markets. A study of the European market suggests a clinical testing

products market in excess of 4000 million US$ in the 1990s (BiomedicalBusiness International). In the US, the current biosensor market is already

, ,

million dollars by the turn of the century. This compares with a world market in1985 of 1.5 billion dollars with an estimated growth rate of 9.5%, achieving a

world market of 2 billion in 1990 and then expanding upwards and outwards.

Need for Biosensor

Other Markets. Among the market shares, nearly 50% belongs to the medical

arena (Technical Insights Inc.) with veterinary and agricultural applications


99/106

( g ) y g pp

amounting to a figure of half the size.

Table 1. Fifteen characteristics required in a commercial sensor

Relevance of output signal to measurement environment

Accuracy and repeatabilitySensitivity and resolution

Speed of response

Insensitivity to temperature (or temperature compensation)Insensitive to electrical and other environmental interferenceAmenable to testing and calibrationReliability and self-checking capabilityPhysical robustnessService requirements

Capital costRunning costs and lifeAcceptability by userProduct safety-sample host system must not be contaminated by sensor

Biosensor Market


100/106

USA market projection for biosensors

The biosensors market is expected to grow from $6.72 billion in 2009 to $14.42 billion

in 2016 (Yahoo Finance).

How to start a biosensor company

Biosensors are getting really popular. For the newbie, biosensors are like the machines which are

trained to recognize biological responses and convert them into mechanical signals. One of the best


101/106

examples of biosensors is blood sugar monitors which are capable of detecting blood sugar levels

almost instantly and accurately.

Biosensors are one of the most innovative and exciting fields now in the market for healthcare.

Irrespective of the weak economy and doubtful future outlook most industry experts are predicting a

60% annual growth rate for the biosensor industry and most of the drive comes from health-care and

. ,

diabetics as well as kidneys for transplants but several companies are racing to provide artificial

substitutes which combine human cells with innovative engineering as standby or bridge transplants!

Innovative medical biosensor devices which can be used as bridges till organs become available are

now the target of several biosensor companies! Several other industries have also turned their

interests towards the use of biosensors like the food industry for food quality appraisal as well as

environmental agencies for rapid and accurate environmental monitoring. Several surveys have

estimated a surge of about 12,000,000,000 per year in the healthcare industry alone.

How to start a biosensor company

Putting up a biosensor company however will require extensive research and development into this

extremely technology sensitive field. The research required to innovate biosensors is extremely original


102/106

and involves several disciplines of physics, biochemistry, human anatomy, laboratory sciences and

bioreactor science, physical chemistry, human bodily reactions, electrochemistry, electronics and software

engineering. As a result you will need trained staff of the highest caliber to work on your research and

development wing to get the best biosensors out in the market for different purposes. The current market

is flooded with potentiometric as well as amperometric biosensors which use special colorimetric paper

enzyme str ps. e potent a or more an etter sensors an su st tute organs s a oon or pat ents w o

are suffering life-threatening diseases.

Constant innovation will require highly paid and talented staff and you will also require a precision

modern fully automated factory to produce the technique sensitive biosensors for marketing and sales!

The ideal biosensor if you manufacture should be tiny, swift, easy to handle, cheap and easily available. It

should last for a long time and should be able to be stored in different weather conditions. The

possibilities of having your own patented innovative design can result in several more biosensors based

on the same research model and used for different detection purposes.


103/106


104/106


105/106


106/106

bm 519 nanotechnology in bio sensors and biosensor market

Documents