mb-jass 2006 nathalie munnikes, tum...biosensors and bioelectronics 20, 2005 [5] enzyme...
TRANSCRIPT
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Commercial Biosensors - Nathalie Munnikes - TUM 1
Commercial BiosensorsCommercial Biosensors
MB-JASS 2006Nathalie Munnikes, TUM
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OverviewOverviewWhat is a biosensor?The biological component
Immobilization
Some transducer principlesElectrochemicalOpticalAcoustic-Piezoelectric
Some application areasDiabetesMarine observation
Conclusion
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IntroductionIntroduction
Aim: combining the specificity and sensitivity of biological systems with the computing power of the microprocessor
[1]
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The AnalyteThe Analyte
In principle any substance that takes part in a biochemical process:Anorganic:
– Gases– Ions (pH)– Heavy metals
Organic:– Organic acids ( proteins)– Carbohydrates (sugars)– Urea (NH2)2CO
More generally: any unit, (part of) which is involved in a biochemical process:Microorganisms(Microbial) cells
AntibodiesAntigens
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The BioreceptorThe Bioreceptor
EnzymesAntibodiesNucleic acidsReceptors
Organisms, slices of tissue, cells, organelles, membranes
Any biological substance that can attach itself to a particular analyte:
...and unpurified material containing such a substance:
[1]
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The Bioreceptor (2)The Bioreceptor (2)
EnzymesAntibodiesNucleic acidsReceptors
Catalytists
Based on bioaffinity:binding & labelling
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Example: labelling antibodiesExample: labelling antibodies
Antibodies
Oxygen electrode
Label: catalase
Antigens
Catalase: 2 H2O2 2 H2O + O2
[11]
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The Bioreceptor (2)The Bioreceptor (2)
EnzymesAntibodiesNucleic acidsReceptors
Catalytists
Based on bioaffinity:binding (& labelling)
Based on hybridization:binding of a unique
DNA/RNA sequence
Based on a physiological responsee.g. neurotransmitters
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Receptors: specificity vs. stabilityReceptors: specificity vs. stability
[1]
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ImmobilizationImmobilization
adsorption
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ImmobilizationImmobilization
Polymer gel
adsorptionentrapment
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ImmobilizationImmobilization
Membrane
adsorptionentrapment
microencapsulation
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ImmobilizationImmobilization
adsorptionentrapment
microencapsulation cross-linking
Stabilises adsorbed material
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ImmobilizationImmobilization
Designed bond
adsorptionentrapment
microencapsulation cross-linking
covalent binding
[1]
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Example: covalent bondingExample: covalent bonding
Carboxyl group
Amine group
[11]
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Transducers: an overviewTransducers: an overviewElectrochemical:
Optical:
Mechanical-piezoelectricAcoustical-piezoelectric
Calorimetric
ConductimetryField Effect Transistors
Internal Reflection Spectroscopy – Surface Plasmon Resonance (SPR)
PotentiometryAmperometry
Ultraviolet-visible absorptionLuminescenceLaser light scattering
Surface Acoustic Wave (SAW)
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Electrochemical transducersElectrochemical transducersDifference between indicator
and reference electrode potential at equilibrium (i.e.
zero current)
PotentiometryAmperometryConductimetryField Effect Transistors
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The electrochemical cellThe electrochemical cell
Gibbs free energy of a half cell (Ox + ne- = Red):
∆G = -nFE = -RT ln K
Measured potential:Ecell = Eind - Eref
Nernst equation for the electromotive force of a half-cell:
E = E* + RT/nF · ln (aOx/aRed)
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IonIon--selective Electrode (ISE)selective Electrode (ISE)
[1,10]
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Electrochemical transducersElectrochemical transducersDifference between indicator
and reference electrode potential at equilibrium (i.e.
zero current)
PotentiometryAmperometryConductimetryField Effect Transistors Current flowing between
working and reference electrode
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AmperometryAmperometry
At t0 a voltage is applied over the electrodes, causing the cell to “recharge”.The diffusion rate of fresh Ox decreases.Fick’s law: dC/dt = D * d2C/dC2
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Amperometry (2)Amperometry (2)
The diffusion-limited current decays over time:id = nFADCOx / √(πt)
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Electrochemical transducersElectrochemical transducersDifference between indicator
and reference electrode potential at equilibrium (i.e.
zero current)
PotentiometryAmperometryConductimetryField Effect Transistors Current flowing between
working and reference electrode
Transistors where the gate metal has been replaced by a chemically
sensing surface
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Field Effect TransistorField Effect Transistor
1 Silicon substrate2 Insulator SiO2/Si3N43 Furrow Metals4 Lacune (gap)5 Selective coating
[1,9]
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Optical transducersOptical transducers
Ultraviolet-visible absorptionLuminescenceInternal Reflection Spectroscopy
Surface Plasmon Resonance (SPR)
Laser light scattering
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Example: luminescenceExample: luminescence
Combining chemiluminescence and fluorescence
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Total Internal Reflection (TIR)Total Internal Reflection (TIR)
Snell’s law:n1sin θ1 = n2sin θ2
θc = sin-1(n2/n1)
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The evanescent waveThe evanescent wave
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Total Internal Reflection Total Internal Reflection FluorescenceFluorescence
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Plasmons & TIRPlasmons & TIR
A plasmon is a quasiparticle, belonging to a collective oscillation of the free electron gas in (semi)conductors.
An evanescent wave at a dielectric/conducting medium interface can excite surface plasmons
[12]
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Plasmons & TIR (2)Plasmons & TIR (2)
Gap in the reflected light intensity
How to involve biomaterial in this?
Thin conducting layer with biomaterial on the other side. A small change in refractive index of the biomaterial causes a large shift of θ.
[12]
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Surface Plasmon ResonanceSurface Plasmon Resonance
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PiezoelectricityPiezoelectricity
Applied stress: T = cS - eTEElectric displacement (polarization):D = eS + εE
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The Rayleigh Surface WaveThe Rayleigh Surface Wave
Amplitude ~ 10Å
[1]
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Surface Acoustic Wave TransducerSurface Acoustic Wave Transducer
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Surface Acoustic Wave TransducerSurface Acoustic Wave Transducer
Resonance frequency:F0 = VR/λ = VR / 4d
[1]
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OverviewOverviewWhat is a biosensor?The biological component
Immobilization
Some transducer principlesElectrochemicalOpticalAcoustic-Piezoelectric
Some application areasDiabetesMarine observation
Conclusion
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Application areasApplication areas
Health industryBlood glucose sensors for diabetes patients
Food industry– Determination of the composition– Degree of contamination:
Pathogens, pesticides, microorganisms, toxins– On line control of the fermentation process
Natural environmentWater quality control
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History of the biosensorHistory of the biosensor
Invented by Clark in 1962Commercialized in 1974World market in 2004:$5 billion
Leland C. Clark Jr. (1918-2005) First commercial glucose biosensor
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DiabetesDiabetes
Medical disorder, where the hormone that regulates uptake of sugars fails
high blood glucose levelType 1: lack of insulinType 2: lack of insulin sensitivity2006: 171 million people, 2030: twice as much#6 of the leading causes of death in the US
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Blood glucose biosensorsBlood glucose biosensors
Replaced the reflectance metersNow: 85% of the world market for biosensors
[4]
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Marine observationMarine observation
Nitrate biosensor
Nutrient concentrations, algal biomass, species composition, water quality (oxygen, toxins etc.)
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Commercial success & Commercial success & expectationsexpectations
Commercial succes due to popularity in:Academic research (cheap equipment, broad learning field)Politics (improvement of human health / environment; defence against biochemical terrorism)
Sensor type Advantages DisadvantagesSingle use high accuracy and
sensitivity, modest costsIntermittent use fast not precise, very expensiveContinuous use cannot hold calibration yet
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ReferencesReferences
[7] Evanescent wave fluorescence biosensorsC. Taitt, G. Anderson, F. LiglerBiosensors and Bioelectronics 20, 2005
[8] Listening to the brain: microelectrode biosensors for neurochemicalsN. Dale, S. Hatz, F. Tian and E. LlaudetTrends in Biotechnology 23, 2005
[9] Review of the use of biosensors as analytical tools in the food and drink industriesL. Mello, L. KubotaFood Chemistry 77, 2002
[10] Ion-Selective Electrodes (2005)Chemical Sensors Research Group, Warsaw University of Technologyhttp://csrg.ch.pw.edu.pl
[11] Biosensors : an introductionBrian EgginsWiley Teubner, Stuttgart 1996
[12] Surface Plasmon ResonanceArnoud Marquarthttp://home.hccnet.nl/ja.marquart/BasicSPR/BasicSpr01.htm
E-Mail: [email protected]
[1] Lecture “Biochemical Sensors” (2003/04)Jose Garrido, Technische Universität Münchenhttp://www.wsi.tu-muenchen.de/E25/research/DiamondGarrido/josegarrido/lecture.htm
[2] Biosensors: Fundamentals and ApplicationsA. Turner, I. Karube and G. WilsonOxford University Press, Oxford 1987
[3] Biosensors – a perspectivePeter KissingerBiosensors and Bioelectronics 20, 2005
[4] Home blood glucose biosensors: a commercial perspectiveJ. Newman, Anthony TurnerBiosensors and Bioelectronics 20, 2005
[5] Enzyme inhibition-based biosensors for food safety and environmental monitoringA. Amine, H. Mohammadi, I. Bourais, G. PalleschiBiosensors and Bioelectronics 21, 2006
[6] Biosensors for marine applications – we all need the sea, but does the sea need biosensors?S. Kröger, R. LawBiosensors and Bioelectronics 20, 2005
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