Biochip 1

Biochip

Biosensor or bioprocessor that utilizes technologies of modern Biology and Electronics in a micro scale.

Types of BiochipDNA chip

Protein chip

Enzyme chip

Lab-on-a-chip

Biomolecular machine

Biocomputer

Physical methodsare the keys for many biological

problems

DNA sequencing

Protein structure

Spectrophotometry

Mass Spect

Electron microscope

Confocal

Bio-physical methods

DNA sequencing

Protein structure

Spectrophotometry

Mass Spect

Electron microscope

Confocal

Structure Determination

Laboratory of Enzyme and Protein Engineering, Department of Biological Science and Technology, NCTULaboratory of Enzyme and Protein Engineering, Department of Biological Science and Technology, NCTU

An ideal biochip

Size-portable

Save energy-long term usage

Low cost-mass production

High sensitivity-integration

Low sample requirement

Microarray-high thru put

Decreased invasiveness

ASI Atomic Scale IntegrationLSI Large Scale IntegrationGSI Giga Scale IntegrationMSI Medium Scale Integration

Time evolution in computer technology from zero to atomic scale integration (Ciabrera et al., 1991; Nicolini, 1993).

ULSI Ultra Large Scale IntegrationSSI Small Scale IntegrationVLSI Very Large Scale IntegrationZSI Zero Scale Integration

Features and factors of size reduction in microchip-based analysis TIBTECH DECEMBER 1999 (VOL 17)

Laboratory of Enzyme and Protein Engineering, Department of Biological Science and Technology, NCTULaboratory of Enzyme and Protein Engineering, Department of Biological Science and Technology, NCTU

The size matter

Biomolecular Machine

Microtubules and Their Motors

Skeletal Muscle Myosin and muscle contraction

A Proton Gradient Drives the rotation of Bacterial Flagella

DNA as Molecular Machine Construction and operation of

the molecular tweezers.A DNA-fuelled molecular machinemade of DNA

Bernard Yurke*, Andrew J. Turber®eld*², Allen P. Mills Jr*, Friedrich C. Simmel* & Jennifer L. Neumann*

NATURE | VOL 406 | 10 AUGUST 2000

Name Sequence Domain 1 Domain 2A 5’ TGCCTTGTAAGAGCGACCAT CAACCTGGAATGCTTCGGAT 3’B 5’ GGTCGCTCTTACAAGGCA CTGGTAACAATCACGGTCTATGCG 3’C 5’ GGAGTCCTACTGTCTGAACTAACG ATCCGAAGCATTCCAGGT 3’F 5’ CGCATAGACCGTGATTGTTACCAG CGTTAGTTCAGACAGTAGGACTCC TGCTACGA 3’5’ GGTCGCTCTTACAAGGCA CAGCTAGTTTCACAGTGGCAAGTC 3’5’ GCAGGCTTCTACATATCTGACGAG ATCCGAAGCATTCCAGGT 3’F5’ CGCATAGACCGTGATTGTTACCAG CTCGTCAGATATGTAGAAGCCTGC ACGTCGAT 3’F5’ GACTTGCCACTGTGAAACTAGCTG CGTTAGTTCAGACAGTAGGACTCC TGTCCAGA 3’

Biocomputer

Memory-The design of a biochip: a self-assembling molecular-scale memory, Protein Engineering, 1, 295 (1987)

Switching devise-Biochemical switching devise: biomimetic approach and application to neural network study, J. of Biotech, 109, 109 (1992)

Logic gate-A biochemical logic gate using an enzyme and its inhibitor, Biotech Progress (1999)

Wire-Femtosecond direct observation of charge transfer between bases in DNA. Proc Natl Acad Sci USA, 19, 14052 (2000)

Applications of DNA chip and microarray technologyPharmacogenomics (2000) 1(3):289-307

Companies involved in developing microarray DNA-chip technology for pharmacogenomics(from A to V) Pharmacogenomics (2000) 1(3):289-307

Components of a DNA microchip.

Pharmacogenomics (2000) 1(3):289-307

Types of transducer

Electrical-current/voltage (FET, MOS),charge, dielectricity

Optical-absorption, emission, phase change, polarisation/absorption (SPR), opto-ethermal

ThermalMagnetic-NMR, mass spectMechanical, frequency-surface acoustic

wave, quartz balance

Electrochemical Sensors

Principle: Anode: semi-oxidation reaction

Cathode: semi-reduction reaction

Example: Biofuel cell

Anode: glucose gluconolactone + 2H+ + 2e-GOD

Cathode: O2 + 4H+ + 4e-2H2O

Laccase

Biofuel Cell (J.A.C.S. 2001, 123, 8630)

Electronic Nose(Biosen. & Bioele. 14, 1999 9-18)

Surface Plasma Resonance (SPR)

Nanowire FET (Sience 293, 17, August, 2001)

Semiconductor Devices as Sensors of Biological Reactions

Enzymatic Reaction

Mass

Electron

HeatCharge

Light

Modified Electrode

Thermometer

EnzymeFET

Photodiodes SAW