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    Introduction and Overview ofBiosensors and Electrochemistry.

    Prof. Chenzhong LiNanobioengineering&BioelectronicsLab, Department of BiomedicalEngineering, Florida InternationalUniversity, E-mail: [email protected]

    Biosensors and Nano-Bioelectronics

    Lecture I

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    Outlines

    Introduction of the lecture

    Terms and definition

    Rational of a biosensor Types of biosensor

    Applications of biosensors

    Electrochemistry and biosensors

    Nanotechnology in biosensor

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    What is biosensor?

    An important player in 21st century engineering will be the

    biotraditional engineer, the recipient of a traditional engineerstraining and a modicum of exposure to life science. M.H.Friedman, J. Biomechanical Eng, V123, December 2001

    Chemical Sensors:A chemical sensor is a device that transforms chemcial information, rangingfrom the concentration of a specific sample component to total compositionanalysis, into an analytically useful signal IUPAC

    Biosensors: are analytical tools for the analysis of bio-material samples togain an understanding of their bio-composition, structure and function byconverting a biological response into an electrical signal. The analyticaldevices composed of a biological recognition element directly interfaced to asignal transducer which together relate the concentration of an analyte (or

    group of related analytes) to a measurable response.

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    Biosensor Components

    Schematic diagram showing the main components of a biosensor. The bio-reaction (a)

    converts the substrate to product. This reaction is determined by the transducer(b) whichconverts it to an electrical signal. The output from the transducer is amplified (c), processed(d) and displayed (e).

    (http://www.lsbu.ac.uk/biology/enztech/biosensors.html)

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    Defining events in the history of biosensor development

    First bedside artificial pancreas (Miles)1976

    First microbe-based biosensorFirst immunosensor: ovalbumin on a

    platinum wireInvention of the pO2 / pCO2 optode

    1975

    First commercial biosensor: Yellow SpringsInstruments glucose biosensor

    1972/5

    Invention of the Ion-Selective Field-EffectTransistor (ISFET) (Bergveld)

    1970

    First potentiometric biosensor: ureaseimmobilised on an ammonia electrode todetect urea

    1969

    First description of a biosensor: anamperometric enzyme electrode for glucose(Clark)

    1962

    Invention of the oxygen electrode (Clark)1956

    First glass pH electrode1922

    First report on the immobilisation of proteins:adsorption of invertase on activated charcoal1916

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    Biosensor History (cont.)

    BioNMES, Quantum dots, Nanoparticles,Nanocantilever, Nanowire and Nanotube

    1999-current

    LifeScan purchases Inverness Medical's glucose testingbusiness for $1.3billion2001

    Merger of Roche and Boehringer Mannheim to formRoche Diagnostics

    1998

    Launch of LifeScan FastTake blood glucose biosensor1998

    Abbott acquires MediSense for $867 million1996Glucocard launched1996

    i-STAT launches hand-held blood analyser1992

    Launch of the Pharmacia BIACore SPR-based biosensorsystem

    1990

    Launch of the MediSense ExacTech blood glucosebiosensor

    1987

    First mediated amperometric biosensor: ferrocene usedwith glucose oxidase for the detection of glucose

    1984

    First surface plasmon resonance (SPR) immunosensor1983

    First fibre optic-based biosensor for glucose1982

    First fibre optic pH sensor for in vivo blood gases

    (Peterson)

    1980

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    Type of Biosensors (by analytes)

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    Types of Biosensor (by detection mode)

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    Typical Sensing Techniquesfor Biosensors

    Fluorescence DNA Microarray

    SPR Surface plasmon resonance Impedance spectroscopy SPM (Scanning probe microscopy, AFM, STM) QCM (Quartz crystal microbalance)

    SERS (Surface Enhanced Raman Spectroscopy) Electrochemical

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    Biosensor Market

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    Biomedical Diagnostics

    Doctors increasingly rely on testing

    Needs: rapid, cheap, and low tech

    Done by technicians or patients

    Some needs for in-vivooperation, withfeedback

    Glucose-based on glucose oxidaseCholesterol - based on cholesterol oxidaseAntigen-antibody sensors - toxic substances, pathogenic bacteriaSmall molecules and ions in living things: H+, K+, Na+, NO, CO2, H2O2

    DNA hybridization, sequencing, mutants and damage

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    Commercial Glucose Sensors

    Biggest biosensor success story!

    Diabetic patients monitor blood glucose at home

    First made by Clark in 1962, now 5 or morecommercial test systems

    Rapid analysis from single drop of blood

    Enzyme-electrochemical device on a slide

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    Basic Characteristics of a Biosensor

    1. LINEARITY: Maximum linear value of the sensorcalibration curve. Linearity of the sensor must be high for

    the detection of high substrate concentration.2. SENSITIVITY: The value of the electrode response persubstrate concentration.3. SELECTIVITY: Interference of chemicals must beminimised for obtaining the correct result.

    4. RESPONSE TIME: The necessary time for having 95% ofthe response.

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    electrode

    substrate product

    Enzyme

    Apply voltage Measure current prop.

    to concentration of substrate

    Principle of Electrochemical Biosensors

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    Electrochemical GlucoseBiosensor

    Glucose + O2 Gluconic Acid + H2O2

    H2O2 2H+ +O2 +2 e-Pt

    0.6 V vs. SHE

    GOx

    Electrode

    GlucoseO2

    H2O2

    Gluconic Acid

    GOxGOx: Glucose Oxidase

    The first and the most widespreadly used commercial biosensor:

    the blood glucose biosensordeveloped by Leland C. Clarkin1962

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    What Is Nanotechnology?What Is Nanotechnology?

    (Definition from the NNI)

    Research and technology development aimed tounderstand and control matter at dimensions of

    approximately 1 - 100 nanometer the nanoscaleAbility to understand, create, and use structures, devices

    and systems that have fundamentally new properties andfunctions because of their nanoscale structure

    Ability to image, measure, model, and manipulate matter onthe nanoscale to exploit those properties and functions

    Ability to integrate those properties and functions intosystems spanning from nano- to macro-scopic scales

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    The First Nanotechnology

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    Application of Nanotech

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    Nanotech in Daily Life

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    Tools In Nanotechnology

    The main tools used in nanotechnology are four mainmicroscopes

    Transmission Electron Microscope (TEM)

    Atomic Force Microscope (AFM)

    Scanning Tunneling Microscope (STM)

    Scanning Electron Microscope (SEM)

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    Applications

    Biological Sciences Pharmacy Chemistry/Biochemistry Physics Biomedical Eng. Electrical Eng. Mechanical Eng. Material Eng. Bioinformatics

    Nano-Biotechnology

    Carbon

    nanotubes

    Nanomaterials

    Fullerene

    Nano-

    particles

    Dendrimers

    Biomaterials

    Protein/

    enzymes

    Peptides

    Antigens/

    antibodies

    Neurons

    DNA/RNA

    Cells

    Electronicelements

    Electrodes

    Field-effect

    transistors

    Piezoelectric

    crystals

    STM Tip

    Biosensor

    Medical

    devices

    Solar cell

    Biofuel cell

    Current, Potential, Impedance, Electrical power

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    Nano Materials: Carbon Nanotube-Electrodes; MetallicNanoparticles-sensor probes and electrodes; Nanorod-sensorprobes; Magnetic Particles-sensor probes; Nanowires-FET sensingsystem, quantam dot (AsSe, CdSe, etc.)

    Nanotechnology will enable us to

    design sensors that are muchsmaller, less power hungry, andmore sensitive than current micro- ormacrosensors.

    Bio-Nanomaterial Hybrids: DNA-Np; DNA-CNTs; Drug-Nps, Peptide-

    CNTs, etc.

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    Nano/Micro-Electro-Mechanical Systems (N/MEMS) for SensorFabrication

    BioMEMS/BioNEMS, Lab-on Chip, Microfluidic System, SensorArrays, Implantable Sensor

    SnifferSTAR is a nano-enabled chemicalsensor integrated into a micro unmanned aerial

    vehicle

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    Nanofabrication (Top-Down; Bottom-Up)Nanofabrication

    ! Nanofabrication methods can be divided into two categories:

    Top down approach Micron scale lithography: optical, ultra-violet, FocusedIon BeamElectron-beam lithography 10-100 nm

    Bottom up approach

    Chemical self-assembly: Man-made synthesis (e.g.carbon nanotubes); DNA SAMs,Biological synthesis (DNA,proteins)

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    Nanopore Technology

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    Electrochemistry

    Introduction

    Electrochemistry can be broadly defined as the study of charge-transfer phenomena. As such, the field of electrochemistryincludes a wide range of different chemical and physicalphenomena. These areas include (but are not limited to):battery chemistry, photosynthesis, ion-selective electrodes,

    coulometry, and many biochemical processes. Although wideranging, electrochemistry has found many practical applicationsin analytical measurements.