BIOSENSORS BASED ON SURFACE PLASMON RESONANCE · 2009-07-15 · • Minimum interaction length/volume required (small sample volumes can be analyzed). • Generic technology (combines

1

INSTITUTE OF PHOTONICS AND ELECTRONICSACADEMY OF SCIENCES OF THE CZECH REPUBLIC

BIOSENSORS BASED ON SURFACE PLASMON RESONANCE

JIŘÍ HOMOLA

Bremen 1 July 2009

Institute of Photonics and Electronics, Prague

Biosensors are devices consisting of a biomolecularrecognition element and a sensor hardware,

which translate the binding event between the target molecules and biorecognition element into an output signal.

Sensorhardware

Biomolecularrecognition

element

Target analyte

Non-target substances}Antibodies

ProteinsDNA, RNAPeptidesMIPs

MechanicalElectricalMagneticOptical

BIOSENSORS

2


BIOSENSORS: PRESENT AND FUTURE NEEDS

Environmental monitoring

Food safety

Life sciences and pharmaceutical research

Medical diagnostics

Health care at home Networks of sensors

Personalized health care


Measure refractive index

Measure fluorescence

MAIN TYPES OF OPTICAL AFFINITY BIOSENSORS

• Interferometric sensors (Mach-Zehnder integrated optical interferometer, white light interferometer).

1. Label-based affinity biosensors• Sensors based on fluorescence spectroscopy.

2. Label-free affinity biosensors

• Sensors based on spectroscopy of guided waves (grating coupler, resonant mirror, surface plasmon resonance sensor).

3


SPR Metal

Substrate

Light Beam

Analyte

Dielectric

Incident light

Reflected light

surface plasmon excited by the +1st order

Metallic relief

n2

n1

Ref

lect

ivit

y

Wavelength [nm]

Polychromaticradiation Prism coupler

SPW1 SPW2

Metal layer

Sample

SPR BIOSENSORS: FUNDAMENTALS


CHARACTERISTICS OF SP:

PROPAGATION CONSTANT, β

PROPAGATION LENGTH, Λ

PENETRATION DEPTH, L

m d

m d

ε εωβ=

c ε +ε

Λ=3-30 μm

METAL

DIEL

L =20 nm

L =150 - 400 nm

METAL DIELECTRIC(Vacuum)

A surface plasmon at a metal–dielectric interface.

SURFACEPLASMON

SURFACE PLASMONS

4


Binding-induced propag. constant change:Matching condition:

600 700 800 9000.0

0.2

0.4

0.6

0.8

1.0

Ref

lec

tivi

ty

Wavelength [nm]

2sin Re{ }z pnk

expE i z t

zk

BIOSENSORS BASED ON SPECTROSCOPY OF SURFACE PLASMONS

vol

dn

dK

c

Kretschmann geometry of the ATR method.


SURFACE PLASMON RESONANCE BIOSENSORS: MAIN FEATURES AND BENEFITS

• Direct (can detect analyte in one-step).

• Real-time (binding of analyte to sensor surface can be continuously monitored).

• Label-free (no fluorescent or radioactive labels are required for detection of analyte).

• Minimum interaction length/volume required (small sample volumes can be analyzed).

• Generic technology (combines generic optical technology with receptors specific against particular target analytes).

J. Homola: Surface Plasmon Resonance Based Sensors, Springer, 2006.

5


SURFACE PLASMON RESONANCE SENSOR PLATFORMS


Sensors based on angularspectroscopy of surfaceplasmons: BIAcore S51 (left), BIAcore 3000 (right) .

Applications: biomolecular interaction analysis

SPR SENSORS: COMMERCIAL REALITY

FEATURES:• High resolution (~10-7 RIU )• Temperature controlled• Multiple sensing channels

6


LABORATORY SPR SENSOR SYSTEMS: PLASMON IV

SPR sensor based on spectroscopy of surface plasmons Four parallel sensing

channels Temp. stabilization

(stability < 0.02°C) Flow chamber volume

0.5 μL per channel

1. sensor head 2. spectrometer3. light source 4. peristaltic pump

RI RESOLUTION:< 2×10-7 RIU

OPERATING RANGE:1.32-1.45 RIU

41

2

3

600 650 700 750 800 850 900 950

Channel 1

n=1.33

n=1.32

Lig

ht

Inte

nsi

ty

Wavelength [nm]

Channel 2

n=1.33

n=1.32

Polychromaticradiation

Prism

Channel A Channel B

SP 1 SP 2

Metal layerSample


A portable 8-channel SPRWDM sensor for field use. RI RESOLUTION:4x10-7 RIU

PORTABLE WDMSPR SENSOR FOR FIELD USE

600 650 700 750 800 850 900 950

n=1.33n=1.32

Lig

ht

Inte

nsi

ty

Wavelength [nm]

J. Homola, H. B. Lu, S. S. Yee, Electronics Letters 35, 1105-1106 (1999).P. Adam, J. Dostálek, J. Homola, Sensors and Actuators B 113, 774-781 (2006).

Polychromaticradiation Prism coupler

Channel 1 Channel 2

SPW1 SPW2

Metal layer

Sample

7


NOVEL APPROACH TO SPECTROSCOPY OFSURFACE PLASMONS: SPRCD SENSOR

SPRCD: principle of operation

ADVANTAGES: Low-cost (no spectrometer) Compact Chips compatible with mass

production

Surface plasmon resonance coupler and disperser (SPRCD) simultaneously excites a surface plasmon via 2nd order of diffraction and disperses light diffracted into the 1st diffraction order over a position sensitive detector.

Collimatedbeam of

polychromaticlight

Surfaceplasmon

Detector

1st diffractionorder

SPRCD

O. Telezhnikova, J. Homola, Optics Letters, 31, 3339-3341 (2006).

820 830 840 850 860 870 880 8900.0

0.2

0.4

0.6

0.8

1.0

1.2

n=1.34n=1.32

1st o

rder

eff

icie

ncy

(T

M/T

E)

Wavelength [nm]


SPRCD SENSOR FOR FIELD USE

SENSITIVITY:615 nm/RIU

RESOLUTION:< 3×10-7 RIU

OPERATING RANGE:1.33-1.35 RIU

Laboratory prototype of 6-channel SPRCD sensor.

M. Piliarik, M.Vala, I. Tichý, J. Homola, Biosensors & Bioelectronics, in print, available online.

8


SPR SENSORS WITH ENHANCED SENSITIVITY: LRSPR SENSORS

10 100 10000

5

10

15

20 LRSP cSP

SP

R w

ave

len

gth

sh

ift

[nm

]

Analyte size [nm]

Response to an RI change within a thin layer at the surface of metal.

The enhanced penetration depth provides better sensitivity for detection of large analytes (e.g. bacteria, viruses).

Low-loss Enhanced penetration depth

LRSPfeatures:

Hybrid surface plasmons

E. coli


SPR SENSORS WITH ENHANCED SENSITIVITY: LRSPR SENSORS

SENSITIVITY:54,000 nm/RIU

RESOLUTION:< 2.5×10-8 RIU

R. Slavík, J. Homola, Sensors and Actuators B, 123, 10-12 (2007).

9


Parallelmonochromatic

beam

2D arraydetector

Gold-coated sensor surface

Polarizer

Array of sensingspots

CouplingPrism

Imagingoptics

Sample

RI resolution:3x10-5 RIU *

Detection of nucl. acids10nM (18-mer)**

Detection of proteins1nM (anti-FLAG)***

* Fu, E., et al., Review of Scientific Instruments, 75, 2300 - 2304 (2004).** Lee, H.J., T.T. Goodrich, and R.M. Corn, Analytical Chemistry, 73, 5525 - 5531 (2001).*** Wegner, G.J., H.J. Lee, and R.M. Corn, Analytical Chemistry, 74, 5161 - 5168 (2002).

Typical performance:

Challenges: Operating range. Noise due

to light level fluctuations. Image contrast.

SPR IMAGING SENSOR: PRINCIPLE OF OPERATION AND PERFORMANCE


HIGH-THROUGHPUT SPR SENSOR WITH POLAR. CONTRAST AND SPECIAL MULTILAYERS

SPR imaging with polarization contrast and optical multilayer, system layout and detail of the SPR sensor chip.

Parallelmonochromatic

beam

2D arraydetector

SPR sensor chip

Polarizers

SPR active spot

/4 Waveplate

Imagingoptics

Sample

CouplingPrism

Illuminatedarea

M. Piliarik, H. Vaisocherova, J. Homola, Biosensors & Bioelectronics, 20, 2104 - 2110 (2005).

Surface plasmon

Gold layer

Totally reflected lightIncident light

Light spot

Sensor chip

Glass substrate

TE/TM retardingtitanium layer

Al O spacer2 3

Pair of sensing spots

10


Image of the SPR sensing chip for rows of sensing spots exposed to liquids of

different refractive indices.

HIGH-THROUGHPUT SPR SENSOR WITH POLAR. CONTRAST AND SPECIAL MULTILAYERS

M. Piliarik, H. Vaisocherová, J. Homola, Sens. Act. B, 121. 187 (2007).M. Piliarik, H. Vaisocherová, J. Homola, Biosen. Bioel., 20, 2104 (2005).

RI RESOLUTION:1x10-6 RIU

Refractive index [RIU]

1.301.321.341.361.381.401.421.45

1.30 1.35 1.400

10

20

Spot type I Spot type II

Re

lativ

e in

tens

ity [

%]

Refractive index [RIU]

Optimum operating range

0

1

2

3

4N

orm

aliz

ed s

igna

l

Light intensity vs. refractive index. Structure: Ti layer, Al2O3 layer (200 nm),

and SPR-active Au layer (40 nm).


M. Piliarik, J. Homola, Sensors and Actuators B, 134, 353–355 (2008).

J. Ladd, T. Allen, M. Piliarik, J. Homola, S. Jiang, Analytical Chemistry 80, 4231–4236 (2008).

HIGH-THROUGHPUT SPR SENSOR WITH POLAR. CONTRAST AND ADVANCED REFERENCING

Prism

Waveplate

Flow cellGold layer

Mirror 2

Mirror 1

SPRchip

PolarizerPolarizer

{

A)

B)

C) A)

B)

C)

CC

D

High-throughput SPR imaging sensor with polarization control.

RI RESOLUTION:3x10-7 RIU

11


Sensor output

Surface changes

Sensor signal decomposition

Bulkchanges

Surface changes

Bulkchanges

SPECTROSCOPY OF MULTIPLE SURFACE PLASMONS: DECONVOLUTION OF BULK & SURFACE RI CHANGES

Sensor response decomposition

0 5 10 15

0

2

4

6

8

Bulkchange

SP

R w

avel

eng

th s

hif

t [n

m]

Sufacechange

Time [min]

0

2

4

6

8

BS

A 0

.1m

g/m

l

Bu

ffer

SPR sensor response decomposition into bulk and surface changes.


SPECTROSCOPY OF MULTIPLE SURFACE PLASMONS ON DIFFRACTIVE STRUCTURES

Sensors & Actuators B 113, 774 (2006).

SP

k ( ) + incident 1 k ( )diffracted 1

SP

SP



Light wave, k= k( )

2

Aqueousmedium

Substrate

Gold film

LRSP

Aqueous medium

Gold filmBuffer layerUV curable polymer

Substrate SRSPLRSP

SRSP

SRSP

SP

k ( )incident 2 + k ( )diffracted

Light wave, k= k( )

k ( ) +incident 1 k ( )diffracted

Optics Letters 32, 2903-2905 (2007).Gold film

Substrate Bragg-scattering on 2

Aqueousmedium

Incidentwave

Reflectedwave

Diffraction on 1

SP

kincident k ( )diffracted 1

SP

kincident k ( )diffracted 1 - k ( )Bragg 2

Light wave, k= k( )

2. LR & SR Surface Plasmons

1. Bragg-Scattered Surface Plasmons

3. Plasmons on a multi-diffractive grating

12


-50 0 50 100 150 200

0

4

8

12

4=881 nm

2=736 nm

DS

CB

BSACB

nb=1.3377

nb=1.3354

nb=1.3343

nb=1.3331

nb=1.3319

SP

R w

avel

eng

th

[nm

]

Time [min]

nb=1.3308 CB

CB

CB CB

CBBSA DS

BSA

DS

BSA

DS

1=665 nm

CB

-50 0 50 100 150 200 2500

5

10

15

20

CB

d [

nm

]

Time [min]

CB

BS

AC

BD

SC

BB

SA

CB

CB

DS

BS

A

DS

CB

BS

A

CB

DS

012345

nb

wat

er

nb

1

nb

4

nb

2n

b3

nb [

mR

IU]

0.000.040.080.12

nf [

RIU

]

MULTI-SURFACE PLASMON SPECTROSCOPY FOR DETERMINATION OF REFR. INDEX DISTRIBUTION

SPR response to formation of BSA multilayer. Deconvoluted refractive index of background, thickness and refractive index of a thin BSA multilayer.

P. Adam, J. Dostálek, J. Homola, Sensors and Actuators B 113, 774 (2006).

2

Aqueousmedium

Substrate

Gold film


APPLICATIONS OF SPR BIOSENSORS

13


BIOMOLECULAR RECOGNITION ELEMENTS AND THEIR IMMOBILIZATION

Choice of immobilization technique depends on the type of ligand, size of analyte and specifics of application.

REQUIREMENTS:1. High, controlled density of

biorecognition elements2. Non-fouling background

Structure of alkylthiolself-assembled monolayers.

Biomolecular recognition elements used in SPR biosensors include: antibodies, peptides, proteins, DNA, RNA, etc.


FUNCTIONALIZATION OF SPR BIOSENSORS: ALKANETHIOL ATTACHMENT CHEMISTRY

Gold layerSubstrate

Gold layer

Gold layer

Gold layerSubstrate

Cleaning gold surface

Assembling mixed alkanethiols

Activation carboxylic groups with TSTU

Attaching antibodiesSubstrate

Substrate

14


FUNCTIONALIZATION OF SPR SENSORS USINGSTREPTAVIDIN – BIOTIN CHEMISTRY

SubstrateSubstrate

SubstrateGold layerSubstrate Substrate

Gold layerSubstrate


1. Investigation of molecules & their interactionsReal-time study of molecular interactions allowing determination of specificity, interaction models, kinetic rates, equilibrium constants, thermodynamic constants, and epitope mapping.

SPR BIOSENSORS: MAIN APPLICATION AREAS

2. Detection, identification and quantification of chemical and biological substances.

J. Homola, Chemical Reviews, 108, 462-493 (2008).

• Food safety (foodborne pathogens and toxins)• Medical diagnostics (disease biomarkers, antibodies)• Environmental monitoring (endocrine disrupting

compounds)

15


110 120 130 140

0

1

2

3

4

110 120 130 140

buffer

buffer

d[(A)14

T]

d[(MeOEtO

T)14

T] (#28)

S

ens

or

resp

onse

[nm

]

bufferbuffer

d[(B)14

T]

d[ara(Tpc)14

T] (#9)

Time [min]

SCREENING OF OLIGONUCLEOTIDES WITH MODIFIED LINKAGE FOR ANTISENSE THERAPY

O

PO

T

HO

OO

CH3OCH2CH2O

O TO

PHO

O

O

29 oligonucleotides (dT15) with different structural modifications at concentration of 100nM interacted with bound to rA23 on the sensor surface.

Sensor response to binding of oligonucleotides with selected modified linkages to natural rA23A B

• Rapid screening (YES or NO in 15 min)

• Small sample consumption (0.1-100nM)

• Monitoring kinetics of the oligonucleotide interactions


SCREENING OF OLIGONUCLEOTIDES WITH MODIFIED LINKAGE FOR ANTISENSE THERAPY

0

1

2

3

4

0

1

2

3

4

0

1

2

3

4

0

1

2

3

4

100 120 140

0

1

2

3

4

100 120 140 100 120 140 100 120 140 100 120 140 100 120 140

1.

2. 3. 4. 5.

7.

8. 9. 10. 11. 12.

6.

13.

Sen

sor

resp

on

se [

nm

]

14. 15. 16. 17. 18.

19. 20. 21. 22. 23. 24.

25.

26.

27.

Time [min]

28. 29.

30.

Natural dT15

16


KINETIC ANALYSIS OF OLIGONUCLEOTIDES WITH MODIFIED LINKAGE FOR ANTISENSE THERAPY

0 5 10 15 20 25 30

0.00

0.04

0.08

0.12 III. dT15

Se

ns

or

resp

on

se

[nm

]

Time [min]

4.09e2

2.87e3

2e3

kaT

[M1s-1]

1e-4

1.54e-4

5.7e-5

kdT

[s-1]

112.7

15.2

6.4

KdD

[nM]

0.247.94e-27.05e5III

0.057.21e-34.76e5II

0.033.16e-34.96e5I

KdT

[μM]kdD

[s-1]kaD

[M-1s-1]Oligo

#

Duplex NA

Triplex NA

0 5 10 15 20 25 30

0.0

0.2

0.4

0.6

0.8

II. d[(X)14

T]

O

PO T

HO

OO

OCH3

Time [min]

0 10 20 30 40 50

0.0

0.2

0.4

0.6

0.8 I. d[T(TX)7] (S)

O

PO

THO

OOH

(S)-

Sen

sor

resp

on

se [

nm

]

Time [min]


SPR FOR FOOD SAFETY:DETECTION OF TETRODOTOXIN (TTX)

Binding inhibition detection format

I. INCUBATION (15 MIN)

II. DETECTION OF FREE ANTIBODY

antibodyantigen

Sensor response to eight different concentrations of TTX in PBS

(anti-TTX - 1 μg/ml).

110 115 120 125 130 135 140

0

1

2

3

4

5

6

7

8

0 ng/ml 0.01 ng/ml 0.1 ng/ml 1 ng/ml 10 ng/ml 100 ng/ml 1,000 ng/ml 10,000 ng/ml

Sen

sor

resp

on

se [

nm

]

Time [min]

17


TTX in PBS and 10% PFM (puffer fish matrix):

SPR FOR FOOD SAFETY:DETECTION OF TETRODOTOXIN (TTX)

0.01 0.1 1 10 100 1000 10000

0.0

0.2

0.4

0.6

0.8

1.0

1.2

LOD

No

rmal

ized

sen

so

r re

spo

nse

TTX concentration [ng/ml]

PBS 10% PFM (puffer fish matrix)

Calibrationcurve:

LOD: 1.6 ng/ml

LOD: 0.1 ng/mlDomoic acid:Q. Yu, et al., Sensors &Actuators B, 107, 193-201 (2005).


SPR FOR FOOD SAFETY:DETECTION OF STAPHYLOCOCCAL ENTEROTOXIN BI. DIRECT DETECTION

II. AMPLIFICATION

SPR sensor response to SEB. (SEB concentration - 25 ng/ml, a-SEB

concentration – 3 g/ml).Sandwich detection format

J. Homola et al., International Journal of Food Microbiology, 75, 61-69 (2002).

0 20 40 60 80

-1

0

1

2

3

4

5

Amplification(antibody capture)

Direct detection(target capture)

BSAa-SEB

BSASEB

BSA

SP

R w

avel

eng

th s

hif

t [n

m]

Time [min]

18


1 10

0

2

4

6

8

10

12 Amplified response in milk

Direct resp

on

se [nm

]

Am

plif

ied

res

po

nse

[n

m]

SEB concentration [ng/ml]

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Direct response

Amplified response

SPR FOR FOOD SAFETY:DETECTION OF STAPHYLOCOCCAL ENTEROTOXIN B

SEB in buffer and milk (sandwich format): LOD: 0.5 ng/ml

Calibrationcurve:

Botulinum neurotoxins in buffer, honey (20%): LOD: <1 ng/mlJ. Ladd, et al., Sensors & Actuators B, 130, 129-134 (2008).


SPR FOR FOOD SAFETY:DETECTION OF BACTERIAL PATHOGENS

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

104 5x104 105 106 107

SP

R w

ave

leng

th s

hift

[nm

]

Cell concentration [cfu/ml]

PBS Apple Juice pH 3.7 Apple Juice pH 7.4

SPR sensor response to different concentration of E. coli in buffer and in apple juice

(sandwich detection format).A. D. Taylor, Q. Yu, S. Chen, J. Homola, S. Jiang, Biosensors & Bioelectronics 22, 752 (2006).

LOD:E. coli:

104 cell/mlC. jejuni:

5×104 cell/mlS. typhimurium:

5×104 cell/mlL. monocytogenes:

104 cell/ml

19


SPR FOR MEDICAL DIAGNOSTICS:BIOMARKERS OF ALZHEMIER DISEASE

10 100 1000 10000

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

Sen

sor

resp

on

se [

nm

]

Concentration [ng/ml]

in ACSF in PBS

Binding of 17-HSD10 to the immobilized A.

Detection in buffer and in ACSF: calibration curve.

185 190 195 200 205

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

10 50 1

10000

5000

3000

1000500

100

Sen

sor

resp

on

se [

nm

]

Time [min]

Mitochondrial enzyme 17beta-hydroxysteroid dehydrogenase type 10 (17-HSD10)

Amyloid-beta (A) peptides

K. Hegnerová, et al., Sensors & Actuators B, 139, 69 (2009).Z. Krištofiková, et al., Molecular Biosystems, in print.

LOD: 5 ng/ml


SPR FOR MEDICAL DIAGNOSTICS:DETECTION OF ANTIBODY AGAINST EB VIRUS

SPR sensor response to increasing concentration of anti-EBNA using regenerated peptide surface.

180 210 240 270 300 330

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

Sen

sor

resp

on

se [

nm

]

Na

OH

30m

M

Na

OH

30m

M

NaO

H 3

0m

M

NaO

H 3

0m

M

NaO

H 3

0m

M

anti

-EB

NA

20

00 n

g/m

l

anti

-EB

NA

20

0 n

g/m

l

anti

-EB

NA

20

ng

/ml

anti

-EB

NA

2

ng

/ml

anti

-EB

NA

0.

2 n

g/m

l

bu

ffer

bu

ffer

bu

ffer

bu

ffer

bu

ffer

bu

ffer

bu

fferbu

ffer

bu

ffer

bu

ffer

bu

ffer

Time [min]

Monitoring immobilization of BSA-EBNA peptide

conjugate on gold.

0 20 40 60 80

0

2

4

6

BSA-CMV (reference surface)

BSA-EBNA-1

Glutaraldehyde0.5%

BSA-EBNA-1BSA-CMV50 µg/ml

PBS

PBS

PBS

Sen

sor

resp

on

se [

nm

]

Time [min]

H. Vaisocherová, K. Mrkvová, M. Piliarik, P. Jinoch, M. Šteinbachová, J. Homola, Biosensors and Bioelectronics 22, 1020 (2007).

20


Sensor response to anti-EBNA in buffer (14 binding experiments for each concentration) and in serum.

0.1 1 10 100 1000

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Sen

sor

res

po

nse

[n

m]

Concentration of anti-EBNA-1 [ng/ml]

anti-EBNA-1 in 10 mM PBS, 0.5% BSA anti-EBNA-1 in 10 mM PBS,

0.5% BSA, 1% human serum

ACHIEVED LOD:0.2 ng/ml

VARIABILITY:< 15 per cent

H. Vaisocherová, K. Mrkvová, M. Piliarik, P. Jinoch, M. Šteinbachová, J. Homola, Biosensors and Bioelectronics 22, 1020 (2007).

SPR FOR MEDICAL DIAGNOSTICS:DETECTION OF ANTIBODY AGAINST EB VIRUS


SPR FOR ENVIRONMENTAL MONITORING:DETECTION OF ENDOCRINE DISRUPTORS

Inhibition assay detection format.

BSA-EDC conjugate

I. INCUBATION

II. DETECTION OF FREE ANTIBODY

Antibody

Analyte

Gold layerSubstrate

0 5 10 15 20 250.0

0.2

0.4

0.6

0.8

1.0

1.2

Sen

sor

resp

on

se

Time [min]

0 ng/ml, 0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml

Detection of atrazine using inhibition assay. Kinetic response

to unreacted antibody.

21


Calibration curves for detection of atrazine (ATR), 2,4-dichlorophenoxyacetic acid (24D), 4-

nonylphenol (4NP) and benzo[a]pyrene (BaP).

ACHIEVED LODS:ATR – 70 pg/ml

BaP – 50 pg/ml

4NP – 260 pg/ml

2,4-D – 160 pg/ml

J. Dostálek, J. Přibyl, J. Homola, P. Skládal, Anal. and Bioanal. Chemistry 389, 1841–1847 (2007).

SPR FOR ENVIRONMENTAL MONITORING:DETECTION OF ENDOCRINE DISRUPTORS

10-3 10-2 10-1 100 101 102 1030.0

0.2

0.4

0.6

0.8

1.0

atrazinebenzo[a]pyrene4-nonylphenol2,4-dichlorophenoxyacetic acid

Se

ns

or

resp

on

se [

a.u

.]

Analyte concentration [ng mL-1]


SUMMARY

Optical biosensors based on spectroscopy of surface plasmons provide label-free, fast, specific and sensitive alternative to traditional laboratory analytical techniques.

Limits of detection for small and medium-size analytes are at practically relevant (sub-)ng/ml levels.

SPR biosensor technology can benefit important sectors such as medical diagnostics, environmental monitoring, food safety and security.

Various SPR sensor platforms and functionalizationchemistries are available to meet needs of specific applications.

Documents

BIOSENSORS BASED ON SURFACE PLASMON RESONANCE · 2009-07-15 · • Minimum interaction length/volume required (small sample volumes can be analyzed). • Generic technology (combines