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

Types of Biochip DNA chip Protein chip Enzyme chip Lab-on-a-chip Biomolecular machine Biocomputer

Physical methods are 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

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

ULSI Ultra Large Scale Integration SSI Small Scale Integration VLSI Very Large Scale Integration ZSI Zero Scale Integration ASI Atomic Scale Integration LSI Large Scale Integration GSI Giga Scale Integration MSI Medium Scale Integration Time evolution in computer technology from zero to atomic scale integration (Ciabrera et al., 1991; Nicolini, 1993).

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

The size matter

Biomolecular Machine Microtubules and Their Motors Skeletal Muscle Myosin and muscle contraction A Proton Gradient Drives the rotation of Bacterial Flagella

A DNA-fuelled molecular machinemade of DNA 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 2 A 5’ TGCCTTGTAAGAGCGACCAT CAACCTGGAATGCTTCGGAT 3’ B 5’ GGTCGCTCTTACAAGGCA CTGGTAACAATCACGGTCTATGCG 3’ C 5’ GGAGTCCTACTGTCTGAACTAACG ATCCGAAGCATTCCAGGT 3’ F 5’ CGCATAGACCGTGATTGTTACCAG CGTTAGTTCAGACAGTAGGACTCC TGCTACGA 3’ b 5’ GGTCGCTCTTACAAGGCA CAGCTAGTTTCACAGTGGCAAGTC 3’ g 5’ GCAGGCTTCTACATATCTGACGAG ATCCGAAGCATTCCAGGT 3’ FBg 5’ CGCATAGACCGTGATTGTTACCAG CTCGTCAGATATGTAGAAGCCTGC ACGTCGAT 3’ FCb 5’ 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 technology Pharmacogenomics (2000) 1(3):289-307

(from A to V) Pharmacogenomics (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 Thermal Magnetic-NMR, mass spect Mechanical, frequency-surface acoustic wave, quartz balance

Electrochemical Sensors Principle: Anode: semi-oxidation reaction Cathode: semi-reduction reaction Example: Biofuel cell

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 SAW Photodiodes Mass Light Enzymatic Reaction Modified Electrode Electron EnzymeFET Charge Heat Thermometer