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Introduction to Introduction to BiosensorsBiosensors

Prof. Xingwei WangProf. Xingwei Wang

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Brain StormBrain Storm

What do you think of biosensor?What do you think of biosensor?

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Brain StormBrain Storm

What do you think of biosensor?What do you think of biosensor?

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Significance & Great DemandsSignificance & Great Demands

Food safety

Public Health Pathology

Criminology

Civil defense

Environmental Monitoring

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Brief HistoryBrief History1956, Prof. Clark, Father of biosensor concept, Invention of the1956, Prof. Clark, Father of biosensor concept, Invention of the oxygen oxygen electrodeelectrode1962, First description of a biosensor1962, First description of a biosensor1972/5, First commercial biosensor: Yellow Springs Instruments g1972/5, First commercial biosensor: Yellow Springs Instruments glucose lucose biosensorbiosensor1975, First immunosensor1975, First immunosensor1980, First fibre optic pH sensor for 1980, First fibre optic pH sensor for in vivoin vivo blood gasesblood gases1983, First surface plasmon resonance (SPR) immunosensor1983, First surface plasmon resonance (SPR) immunosensor1987, Launch of the MediSense ExacTech1987, Launch of the MediSense ExacTech™™ blood glucose biosensorblood glucose biosensor1990, Launch of the Pharmacia BIACore SPR1990, Launch of the Pharmacia BIACore SPR--based biosensor systembased biosensor system1992, i1992, i--STAT launches handSTAT launches hand--held blood analyserheld blood analyser1996, Abbott acquires MediSense for $867 million1996, Abbott acquires MediSense for $867 million1998, Launch of LifeScan FastTake blood glucose biosensor 1998, Launch of LifeScan FastTake blood glucose biosensor 1998, Merger of Roche and Boehringer Mannheim to form Roche 1998, Merger of Roche and Boehringer Mannheim to form Roche DiagnosticsDiagnostics2001, LifeScan purchases Inverness Medical's glucose testing bus2001, LifeScan purchases Inverness Medical's glucose testing business iness for $1.3billionfor $1.3billion

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What is a BiosensorWhat is a BiosensorA device that uses biological components e.g. enzymes to indicate the amount of a biomaterial

Trace biomaterial?

– Unnecessary (Eg. Metal ion, etc.)

Quantitative results?

– Unnecessary (Eg., Pregnancy test)

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ComponentsComponentsBio Recognition Element

Enzymes; Antibodies; Receptors; Whole cells...

Electrochemical

Optical

Transducer

Signal Output

Requires: Sample Immobilization

Requires:

Simple read out and data interpretation;

Easy to use;

Quick response.

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Performance FactorsPerformance Factors

Sensitivity: Concentration; weightSensitivity: Concentration; weightSpecificity/Selectivity: Specificity/Selectivity: discriminate between substratesSpeed: BenchSpeed: Bench-->Chip>Chip-->Real Time>Real TimeAccuracy: False signalAccuracy: False signalCostCostEasy to useEasy to useLife timeLife time

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Biosensing for MacromoleculesBiosensing for Macromolecules

Steps:Steps:ImmobilizationImmobilizationMixingMixingWashing the nonWashing the non--specific bindingsspecific bindingsSignal transductionSignal transduction

Markers:Markers:EnzymesEnzymesFluorescence tagsFluorescence tagsRadioactive tagsRadioactive tags

Molecular:Molecular:WastonWaston--Crick Base Crick Base pairingpairingAntibodyAntibody--Antigen Antigen bindingbinding

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ImmunosensorImmunosensor

Antibody can be againstAntibody can be againstBacteriaBacteriaComplex carbohydratesComplex carbohydratesSmaller organic moleculesSmaller organic molecules

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DNA Complementary ChainsDNA Complementary Chains

Four nitrogen basesFour nitrogen basesComplementary chainsComplementary chains

C

G

A

T

C G

A T

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Six StepsSix Steps1)1) Select the singleSelect the single--stranded capture DNA sequencestranded capture DNA sequence2)2) Attach the capture DNA strand to a probeAttach the capture DNA strand to a probe3)3) Introduce the samples to be identified to the probesIntroduce the samples to be identified to the probes4)4) Hybridization will occur if the sample is Hybridization will occur if the sample is

complementary with the capture sequence on the complementary with the capture sequence on the probeprobe

5)5) Wash away the remaining unattached samplesWash away the remaining unattached samples6)6) JudgmentJudgment

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TransducerTransducer

Electrochemical (Potentiometric, Electrochemical (Potentiometric, Voltammetric, Amperometry, Conductimetric)Voltammetric, Amperometry, Conductimetric)Optical (Fluorescence, Absorbance, Light Optical (Fluorescence, Absorbance, Light scattering, Refractive index)scattering, Refractive index)Mechanical, Thermal, Piezoelectric, MagneticMechanical, Thermal, Piezoelectric, Magnetic

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Glucose SensorGlucose Sensor

http://www.ul.ie/elements/Issue6/Biosensors-%20Elements.htm

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MicrocantileversMicrocantilevers

From http://www.ornl.gov/info/ornlreview/rev29_3/text/biosens.htm

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Medical TelesensorMedical Telesensor

From http://www.ornl.gov/info/ornlreview/rev29_3/text/biosens.htm

• Military: Locate wounded soldiers• Domestic: Intensive patients

• An array of chips to monitor body functions• Wireless transmission

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MiniaturizationMiniaturization

• Infrared microspectrometer• Size of a sugar cube

From http://www.ornl.gov/info/ornlreview/rev29_3/text/biosens.htm

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Broad Potential ApplicationsBroad Potential Applications

(Picture from www.primordial.com/.../Hardware_Soldier_w640.png)

Warfighter Physiological Status Monitoring (WPSM): remote triage of injured Soldiers

Heart rate, breaths taken, skin temperature and ballistic impact

Foster-Miller (Waltham, Mass.) Putting these sensors on a belt that's sewn into a shirt

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BenefitsBenefits

Industry Military

Academia

Biosensor

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Challenges and TrendChallenges and Trend

CostCostSensitivitySensitivitySelectivitySelectivitySpeedSpeedSmall?Small?Ease to use?Ease to use?

CheapCheapSensitiveSensitiveSelectiveSelectiveSpeed Speed PortablePortableSimpleSimpleIntegratedIntegratedMass producedMass producedMultiple analytesMultiple analytes

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Multidisciplinary NatureMultidisciplinary Nature

Biosensor Chemistry

Biology

PhysicsInstrumentation

Electronics

OpticsMarket

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Worldwide Biosensor Vendor Market, Worldwide Biosensor Vendor Market, 20032003

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References (Reading List 1)References (Reading List 1)

http://www.ornl.gov/info/ornlreview/rev29_3/text/biohttp://www.ornl.gov/info/ornlreview/rev29_3/text/biosens.htmsens.htmhttp://www.cranfield.ac.uk/biotech/sensors/history.hthttp://www.cranfield.ac.uk/biotech/sensors/history.htmmhttp://www.cranfield.ac.uk/biotech/sensors/events.hthttp://www.cranfield.ac.uk/biotech/sensors/events.htmmSensors in Biomedical applications Sensors in Biomedical applications -- fundamentals, fundamentals, technology and applications, by Gabor Harsanyi, technology and applications, by Gabor Harsanyi, ISBN: 1ISBN: 1--5667656676--885885--3, CRC Press; 20003, CRC Press; 2000

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Who I am?Who I am?EducationEducation

MS,MS, Ph.D., Electrical Engineering Virginia TechPh.D., Electrical Engineering Virginia TechCertificate, Future ProfessoriateCertificate, Future Professoriate Virginia TechVirginia Tech

http://faculty.uml.edu/xwang/http://faculty.uml.edu/xwang/ContactContact

Office Hours: Wednesday 3:30 am Office Hours: Wednesday 3:30 am –– 5:30 pm;5:30 pm;or, make an appointmentor, make an appointmentPhone: 978Phone: 978--934934--19811981Office:Office: BL 421ABL 421AEmail:Email: Xingwei_Wang@uml.eduXingwei_Wang@uml.edu

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SyllabusSyllabus

http://faculty.uml.edu/xwang/16.541/syllabus.hhttp://faculty.uml.edu/xwang/16.541/syllabus.htmtmThe account name: Class_WangThe account name: Class_WangPassword:Password: Circuit34567Circuit34567

Literature ReviewLiterature ReviewReportReportPresentationPresentation

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Grading PolicyGrading PolicyAttendance 10%

Presentation I 10%

Report I 10%

Presentation II 10%

Report II 10%Final Presentation 25%Final Report/Project 25%

Total 100%

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Project topicsProject topics

1.1. Ultrahigh sensitive biosensorsUltrahigh sensitive biosensors2.2. Fast response biosensorsFast response biosensors3.3. InIn--vivo blood pressure sensor (St. Jude vivo blood pressure sensor (St. Jude Medical)Medical)4.4. Intravascular ultrasound imaging (IVUS) Intravascular ultrasound imaging (IVUS) (Volcano)(Volcano)5.5. Biosensor integration/miniaturizationBiosensor integration/miniaturization6.6. Optical coherence tomography (OCT)Optical coherence tomography (OCT)7. 7. Glucose sensorGlucose sensor8. 8. NanoNano--BiosensorBiosensor

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Class ScheduleClass Schedule

Tentative. Please check frequently for updates. Tentative. Please check frequently for updates. Lecture topics do NOT necessarily follow the Lecture topics do NOT necessarily follow the order of the schedule.order of the schedule.Topic contents may need more or less time Topic contents may need more or less time than what is allocated. than what is allocated.

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About YouAbout You……

You areYou are……??