Micro-Nano Technology for Genomics and Proteomics BioMEMs - Ozkan

526

Electronic microarray technology (cont.) overview of, 4

nanochip array and nanochip workstation 5–6, 16

nanochip electronic microarrays, capabilities of, 8

Electronic microarrays applications of, 8

cell separation, 12, 61, 63, 121, 145–146 forensic detection, , 3, 10–12

gene expression profiling, 41–42 molecular diagnostics, 10

Electronic multiplexing, 10 Electronic pumps

dielectrophoretic, 312 electrohydrodynamic, 312 electrokinetic, 312

Electroosmotic fluid flow, 106 Electro-osmotic pumping, 312 Electrophoresis

capillary, constant denaturant, 449 gel

denaturing gradient, 449 temperature gradient, 449

Electrophoresis-based detection technologies, for sequencing, 382

ELISA. See Enzyme linked immunosorbant assay Environmental chamber, 66

Enzyme linked immunosorbant assay (ELISA), 50, 340

Enzyme-based biosensors, 51

Enzymes, 48, 51–52, 96, 137–138, 140, 163, 173, 204

Epitope mapping

B-cell, peptide arrays by, 298 multipin technology

anti-β endorphin, 285

monoclonal antibodies, 128, 214–215 polyclonal serum, 224

Epoxy-modified surfaces, chemistry of, 193 Ethanol, 71

ethylene diamene tetra acetic acid (EDTA), 70 hydrogen peroxide, 69

on neurons, visualization of physiological changes due to effect of, 80–82

on osteoblasts, visualization of physiological changes due to effect of, 81, 83–84

pyrethroid, 69 Ethanol sensing, 71

single neuron sensing, 71 single osteoblast sensing, 71

Ethidium bromide and SYBR Green, DNA intercalating dyes, 24

5 -Exonuclease activity of Taq DNA polymerase, 28 Export of tRNAs in Xenopus oocytes, 504

INDEX

Extra cellular multiple-site recording probes, 59 Extracllular potential based biosensors, 58

microelectrode array technology, 60 signature patterns of specific chemical

agent, 60

Extruded quadrupolar traps, 109

FAMTM, 26

FarWestern analysis, 133

Fast Fourier Transformation (FFT) analysis, 65, 69

Fetal cells

DEP behavior of, 118 in maternal blood, 145

FFT. See Fast Fourier Transformation analysis Fibroblast growth factor, basic (bFGF), 68 Field effect transistors (FET), 61

Field flow fractionation, 109

Field-induced cell destruction, on set of, 124 Filter Binding assay, radioactive, 19 Fingerprinting, restriction digest 376

FISH. See Fluorescence in situ hybridization FLAG epitope peptides, 171

FLAG-tag, 194

Fluid flow, synchronized pulses of, 109 Fluo-3, 80

Fluorescence based cell biosensors, 53 fluorescence imaging, 54 fluorescent reagents

fluorescence resonance energy transfer, 28, 54 green fluorescent protein, 54

Fluorescence biosensor, 54

Fluorescence DNA hybridization assay, 442 Fluorescence energy transfer techniques (FRET), 54 Fluorescence in situ hybridization (FISH), 370 Fluorescence polarization (FP) PKA assay,

antibody-based, 19

Fluorescence polarization anisotropy (FPA), 484 Fluorescence resonance energy transfer (FRET), 28,

30, 54, 296, 408, 429, 443 Fluorescence spectroscopy, 54, 470–472 Fluorescence–kinetic detection methods, 25

gene, 33

Fluorescent competitive allele specific polymerase chain reaction, 449

Fluorescent detection system, 144 Fluorescent reporter dye, 26

Fluorophore with non-overlapping emission curves, 410

Fluorophore, 37 acceptor/donor, 30–31, 55

Fluorosilanes, 61 Forensic DNA profile

database of, 10 polymorphic STR loci, 10

INDEX

Forster resonant energy transfer mechanism, 146

process, 139

Fourier transformation (FFT) techniques, 65 “Frequency modulation”, 69

FRET. See Fluorescence resonance energy transfer FUN effect, 123

Fungal pathogens in Candida dubliniensis, 429

GABAA activation, 76

GAPDH target, amplification plots for serial dilutions of, 33

Gene chip sequencing arrays, 452 Gene detection, in vitro, 403

allele discrimination, 409 mutation detection, 409 pathogen detection, 408

Gene expression analysis TaqMan hydrolysis probes in, 29

Gene expression analysis, application of technologies for, 23

Gene expression of phage, 486 Gene expression profiling methods

with cDNA arrays, 41

with oligonucleotide arrays, 42

Gene expression profiling utilizing microarray technology and RT-PCR, 23

amplification efficiency of target/reference genes, 32, 34

analytical sensitivity and dynamic range, 33–34 cDNA arrays, 35–36

comparative threshold method, 31 microarrays, 32

printed oligonucleotide microarrays, 36Real-Time PCR (RT-PCR), 23–25

qualification of gene panels using RT-PCR, 32 real-time RT-PCR summary, 32 reproducibility and precision, 34

standard curve method, 31–32 technology platforms, 35

Gene expression, posttranscriptional, regulation of, degradation of mRNA, 421

Gene fluorescent detection of, 3 Gene sequencing, shotgun, 378–389 GeneChip microarrays, 37

General purpose interface bus (GPIB) control, 67 Genes, identification of, using hybrid ribozymes, 513 Genetic marker, clones cluster of, 370

Genetic variation, detection of, 449

Genome project coordination, challenges for, 394 after Celera, 392

before Celera, 386 during Celera, 388

Genome sequencing pipeline, 369 Genomic DNA, haplotype structure of, 452

527

Genomics and proteomics, application of electronic microarray technology in, 3–18

Genomics, nanochip technology application in, examples of, 4

Genotyping analysis, 145

Genotyping, TaqMan hydrolysis probes in, 29 Glass surface modification/activation via starbust

dendrimer coating, 179

Glass surfaces, multistep functionalization of, 194 Glyceraldehydes-3-phosphate dehydrogenase

(GAPDH), 32 Goniometry, 163

Gyrolab MALDI SP1 sample preparation CD, 358

H19-7 cell line from ATCC, 65

H19-7 cells, 67–68 Hagen–Poiseuille equation, 335

Hairpin nanoprobes for gene detection, 403 in vitro gene detection, 408

pathogen detection, 408

mutation detection and allele discrimination, 409 living cell RNA detection, 418

cellular delivery of probes, 419 intracellular probe stability, 419 intracellular mRNA detection, 411, 428

nanoprobe design issues for homogeneous assays, 405

intracellular RNA targets, 411 cytoplasmic and nuclear RNA, 411 RNA secondary structure, 418 opportunities and challenges, 431

Hairpin probe design, 408

Hammerhead ribozyme, catalytic domain of, 498, 508 Haplotyping, 452

HapMap, 452

Harvester fluorophore, 408

HCV diagnostic applications, TaqMan hydrolysis probes in, 29

Heterogeneous nuclear ribonucleoproteins, 411 HEXTM, 26

High throughput phenotyping, 156

High throughput screening (HTS) situations, 18, 54 High-density electrode arrays, 109

High-density oligonucleotide arrays, 449

High-risk patients, identification by gene expression profiling, 41

High-throughput screening (HTS) kinase assays, 18 HIV diagnostic applications, TaqMan hydrolysis

probes in, 29

HnRNPs. See Heterogeneous nuclear ribonucleoproteins

Hoechst dye, 79–80

Homogeneous DNA hybridization assay, 443 “Hostboards”, 140

HPLC technology, denaturing, 449

528

HTS. See High-throughput screening kinase assays Human cancer cell lines (the NCI-60 panel), 44 Human disease and drug development, SNPs role, and

haplotypes in, 447

detection of genetic variation, 449 disease gene mapping, 450

drug development, 452 evolution, 450 haplotypes, 452

SNP discovery, 448 Human genetic diversity, 452

Human genome sequencing, approaches in construction of chromosome tiling paths, 379 data sharing, 379

Human genome, research network for large-scale sequencing of, 389

Human genome, sequencing, 365

approaches used to sequence human genome, 365 overview, 366

strategy used for sequencing source clones, 368 construction of the chromosome tiling paths,

379

data sharing, 379

challenges for systems integration, 365 methodological challenges for sequencing source

clones:, 1990–1997, 381

challenges for sequencing the entire human genome:, 1998–2003, 386

are there lessons to be learned from the human genome project?,395

Hybridization probes acceptor/donor fluorophore, 30 quanti probe, 31

Hybridization probes, 30–31 Hydrogen peroxide sensing, 72

single neuron sensing, 71 single osteoblast sensing, 71

Hydrolysis probes, 26, 28

IL-1, expression levels of, increased, after LPS treatment, 14

Immobilization of peptides chemoselective, 194 non-selective, 191

Immunoassays electronic, 14

electric field driven, 14 Immunohistochemistry, 77

in situ synthesized oligonucleotide microarrays, 37

Insulin-like growth factor receptor (IGF-IR), human type I, 68

Integrated circuit (IC) technology, 95 Interfacial Polarization, dynamics of, 107 International Prognostic Indicator, 41

INDEX

Intracellular potential based biosensors, 57 chemical warfare agents

soman (GD), 57 VX, 57

Ion channel switches, antibody-modified, 50 Ion channels biosensors, 50

Ion-selective optode detection, 339 Irradiation with UV-light, 193 Irradiation, 182

JOETM, 26

“Knock down” effect in-vivo, 70

“Lego” blocks for nanofabrication, 147 “Lymphochip”, 41

“Pick & Place” fabrication process, 137 “SELEX” for systematic evolution of ligands by

exponential enrichment, 129 “Top-down” process, 138

Lanthanide fluorescent, complexes\labels of, 438 Laser excitation sources, 144

LDPS. See light directed peptide synthesis LED arrays, 189

Leica SP2 UV confocal microscope, 78 Leiden, 10

Leukemia classification, 40 Library screening, 286, 369 Library types, 203

de novo approaches, 203

protein sequence-derived libraries, 204 Ligands

aromatic amine derivative-type, 440 chlorosulfonylated tetradentate β-diketone-type,

439 LightCyclerTM, 31

Light-directed peptide synthesis (LDPS), 187–188 Limit of detection (LOD), 34

Limit of quantitation (LOQ), 34 Lipopolysaccharide-mediated differentiation, 12 Lithography, Dip-Pen nanolithography/scanning

probe, 58

Magnetic tweezers, 467

MALDI. See Matrix-assisted laser desorption ionization sample preparation Maleimidylhexanoate, N-succinimidyl-6-, 170 Maleimidylpropionate, N-succinimidyl-3-, 170

Mapped clones for sequencing, 370 Mapping source clones, strategies for clone insert end sequencing, 370

fluorescence in situhybridization, 370 library screening, 286, 369 restriction digest fingerprinting, 370

Mapping, 131, 162–163

INDEX

Mapping, disease gene, 450 Mass spectrometry, 130

MassARRAY system, by Sequenom 449 Matrix-assisted laser desorption ionization sample

preparation, 287–288

Maxizyme, active/inactive conformation of, 508 Maxizyme, allosterically controllable, design of 509 Maxizymes, 508

design of, 509 generality of, 512

inactivation of oncogene, 510 shortened hammerhead ribozymes, 508

Maxizyme-transduced BV173 cells, 512 Maxwell stress tensor, 107

Maxwell–Wagner interfacial polarization, 107 Mechanical pumps

bubble generation, 312 osmotic pressure, 312 pneumatic pressure, 312 syringe drive, 312 thermal expansion, 312

MeCP2 mutations associated to Rett syndrome, 10 Medical diagnostics, 95, 103

Melting curve single nucleotide polymorphism (MCSNP), 449

Membrane capacitance, 110 Membranes,

acrylic-acid-modified 166 methylester-modified membrane, 166

MEMS (Micro-Electromechanical Systems), 156 MEMS devices

high density data storage devices, 140

Mendelian disorders, identification of disease genes, 447

Methacrylate polymers, 61

MGB EclipseTM (Epoch Biosciences) probe, 31 Michael addition, 170

Micro total analysis systems, 357

Microarray analysis of mRNA stability in yeast, 417 Microarray and fluidic chip for extracellular sensing,

47

antibody based biosensors, 50–51 biosensing system, 51

cell based biosensors, 52 cell culture, 67

neuron culture, 67–68 primary osteoblast culture, 68

cell patterning techniques, 60

cellular metabolism based biosensors, 55 cellular microorganism based sensors, 52 chemical agents, selection of, 65

ethanol, 69

hydrogen peroxide, 69 pyrethroid, 70

ethylene diamene tetra acetic acid (EDTA), 70

529

chemical agent sensing, 70

signature pattern for control experiments, 70–71

dielectrophoresis for cell patterning, 61 dielectrophoresis, basis of, 62 dielectrophoresis, microelectrodes and, 63–64

EDTA sensing, 76 single neuron sensing, 71

single osteoblast sensing, 71 electrical sensing cycle, 70 ethanol sensing, 71

single neuron sensing, 71 single osteoblast sensing, 71

environmental chamber, 66 enzyme based biosensors, 51–52

experimental measurement system, 67–68 extra-cellular potential based biosensors, 59–60 fluorescence based cell biosensors, 53–54 hydrogen peroxide sensing, 73

single neuron sensing, 73–74 single osteoblast sensing, 74–75

impedance based cellular sensors, 55–57 intracellular potential based biosensors, 57–58 ion channel biosensors, 51

nucleic acid based biosensors, 51 physiological changes due to effect of chemical

analytes, visualization of, 80 ethanol on neurons, 80–82 ethanol on osteoblasts, 81, 83–84

hydrogen peroxide on neurons, 83, 85–86 hydrogen peroxide on osteoblasts, 85, 87–89 pyrethroid on neurons, 88–91

pyrethroid on osteoblasts, 91–93 EDTA on neurons, 89

EDTA on osteoblasts, 91 pyrethroid sensing, 74

single neuron sensing, 71 single osteoblast sensing, 71

immunohistochemistry, 77 signal processing, 68

Microarray system, compact disc-based fiber-optic microarray biosensor, 295 immunoassays, 14

piezoelectric inkjet applicator, 295 Microarray technologies, application of, 1

electronic, applications in genomics and proteomics, 3–18

Microarrays applications, 40 cDNA arrays, 35

in situ synthesized oligonucleotide, 37 protein interaction, 224

spotting techniques, 132 printed oligonucleotide, 36

Micro-centrifuge fluidics, 333

530

Micrococcus lysodeikticus, DEP frequency response for, 114–115

Micro-contact printing (µCP), for promoting cell adhesion, 61

Microelectrodes, 63 Microelectronic arrays

for bioresearch, 137

for DNA clinical diagnostics, 140 Microelectronic arrays, applications of, 145 Microelectronic arrays, by Nanogen, for DNA

genotyping diagnostic applications, 141 Microelectronic MEMS devices, heterogeneous

integration of, 140 Microfluidic channel networks, 181 Microfluidic devices

biomedical, 351

clinical diagnostic applications, 351 Microfluidics propulsion techniques, 331 Microlithography, 146

Microlocations, 14 Micromanipulators, 67

Microorganisms, immobilised mixed culture of, 16, 52

Micro-patterning

contact printing techniques, 173 micro-mirror mediated patterning, 181 photolithografic technologies, 179

Microspheres, 147–149 MicrozoomTM optical probe, 66

Miniaturized electronic microarray system, 16 Miniaturized quantitative cell-based assays, 349 Minor groove binder (MGB), 31

Molecular beacon probes configuration, 30

point mutations detection by, 30 polymorphisms detection by, 30 probe-target duplex, 30

Molecular beacons, components of fluorophore, 30

loop, 30 stem, 30 quencher, 412

Molecular gene therapy and gene discovery, engineered ribozymes, efficient tools for, 505

Molecular probes, nanostructured, 4 Motherboards, 140, 147

MPC. See mini-Pepscan cards

MRNA, expression of, inhibition by ribozyme, 512

MRNA, secondary structure, computational programs to predict, 424

Multiarray-based biochip technology, 93 Multiplex hybridization analysis, 11 Multiplex PCR-amplified DNA, 360

INDEX

Multistep functionalization glass surface, 173

pretreated titan surfaces, 168 Myc-tag, 195

Nano chip rmicroarray, 100-site, 4 NanoChip array

assays format, 9 capabilities of, 8 cartridge of, 16 fabrication of, 4–5 permeation layer of, 5 workstation of, 5

NanoChip microarray, active hybridization technology and passive hybridization technologies, 4

Nanochip technology application in genomics, examples of, 11

NanoChipTM cartridge, 7, 143 assembly, 143

NanoChipTM molecular biology workstation, 143 NanoChip workstation, 7–8

Nanoelectronics applications for, 138

nanoelectronic devices, 138 Nanofabrication,

bottom-up processes for, 138–139 DNA chips, 142

Electric field assisted process, 146

Nanogen’s 400-site NanoChiparray and cartridge, 16 Nanogen’s electronic microarray technology, 5 Nanogen’s microelectronic DNA chip device, 8 Nanogen’s Nanochip Workstation, 8

Nanogen’s portable electronic microarray detection, 10, 16

Nanomechanical devices, light powered, 463 Nanoparticles, 137

Nanoparticles, as antennas, 465 solution phase synthesis of, 466 with reactive ligands, 468

Nanoparticles, DEP behavior of, 116 Nanoparticles, in controlling biomolecules, 473

dehybridization of DNA by RFMF heating of nanoparticles, 471

determination of effective temperature by RFMF heating of nanoparticles, 469

selective dehybridization of DNA by RFMF heating of nanoparticles, 471

technical approach, 468 Nanoparticles, RFMF heating of, 467

Nanoprobe design issues for homogeneous assays, 405 Nanoprobes for imaging, sensing and therapy, 401 Nanospheres, 140, 147–148

DNA sequence, 140 production of, 140

Nanotubes, 137–138, 146–147

INDEX

Nanowires, 137

NASBA. See Nucleic acid sequence-based amplification

Necrosis, 84, 88, 224–225, 231 Neuroblastoma cell cultures, 88

Neuronal cultures on microelectrode array, 59 Neuron-EDTA frequency spectrum, 78 Neuron-ethanol frequency spectrum, 72 Neuron-hydrogen peroxide frequency spectrum, 74 Neuron-pyrethroid frequency spectrum, 76

Neurons and osteoblasts, parameters for positive and negative DEP for, 65

NMDA gated channels, 73–74, 83, 86 activation of, 73–74, 86

NMDA gated channels, 83, 86

NMDA receptor gated Cl− and Na+ ion channels, 76 NMDA receptors

N-methyl-d-aspartate (NMDA) receptor dependent, 80

Non contact printing, peptide arrays of by piezoelectric device piezoelectric ink-jets, 204

Non-fluorescent (“dark”) quencher, 28 Northern blotting, 23, 403, 422

Nuclear magnetic resonance (NMR), to study DNA flexibility, 287, 459, 465, 509

Nuclease invader technique, 449 Nuclease mutation detection method, 449 Nucleic acid based biosensors, 51 Nucleic acid fragmentation, 93

Nucleic acid probes, microscale printing of, 36 Nucleic acids, 48, 139, 167, 404, 409, 418, 420–421,

423, 425 Nucleosome formation, 491

Nucleosome reconstitution, 491–492 NUX cleavage site, 513

NUX triplet, 510

OBOC (one-bead one-compound) peptide libraries, 284

encoded, OBOC small molecule combinatorial libraries, 287–288

combinatorial library methods and chemical microarray techniques, 283

OBOC peptide libraries, 283–284 Oligocarbamates, 188

Oligonucleotide (ODN) probes, 419–420 Oligonucleotide microarray expression profiles, 44 Oligonucleotide microarray, 36–37, 39, 43–44, 200,

228, 299

Oligonucleotide microarrays, in situ synthesized Affymetrix GeneChipmicroarrays, 37–38, 42, 44 manufacture by light-directed method, 37

Oligonucleotide microarrays, methods for production of, 39

531

Oligonucleotide probes, microinjection of, 30, 36–37, 144, 404–405, 418–419

OligoWalk Probe/RNA interactions tools, 418 Oncogene, inactivation of, 512

One step grafting procedure, 167

One-bead one-compound (OBOC) combinatorial libraries to chemical microarrays, 287

chemical microarray, application of, 297 cell-binding studies, 300

diagnostic studies, 301

drug discovery and cell signaling, 300 non-biological applications, 304 post-translational modification, enzyme-substrate

and inhibitor studies, 299 protein binding studies, 298

detection methods in chemical microarrays, 299 detection methods to identify post-translational

modification of proteins, 299 identification and characterization of bound

proteins, 296

encoded OBOC small molecule combinatorial libraries, 287

peptide and chemical microarrays, 289 OBOC peptide libraries, 284

CD, microfluidics, fiber optic microarray, multiplex beads, 295

immobilization methods for pre-synthesized libraries, 289

in situ synthesis of microarrays, 292 One-bead one-compound. See OBOC

Optical tweezers, integration of, for manipulation of live cells, 153

Ordered cell networks, 61 Organic quencher molecules, 408 Osmotic pressure pumps, 312

Osteoblast-EDTA frequency spectrum, 79 Osteoblast-ethanol frequency spectrum, 73 Osteoblast-hydrogen peroxide frequency spectrum, 75 Osteoblast-pyrethroid frequency spectrum, 77 Osteoblasts and neurons, parameters for positive and

negative DEP for, 66 Osteoblasts, 87

Oxidized silicon wafers, 142 Oxygen electrode, Clark-type, 53

Oxygen, dissolved, Clark-type probe for, 53

PACs (P1 artificial chromosomes), 368 Paired mismatch (or MM), 37

Parasites, TWD theoretical model for manipulation, separation and characterization of, 119

Pathogen isolation, two-level-stacked microlaboratory, 16

Pathogens, rapid identification of, 16 Patterned surfaces, generalization of, 173, 181 PBFI ester, staining with, 88

532

PBFI, AM ester of, 88

PCR amplicon, biotinylated, 8–9, 143 PCR amplicons, 143

PCR cycle number, 28 PCR cycle number, 28

Pentafluorophenylesters, 167 Pentanedione, 5-(4”-chlorosulfo-1’,

1”-diphenyl-4’-yl)-1, 1, 1, 2, 2-pentafluoro-3, 5-(CDPP), 443

Peptide arrays in proteomics and drug discovery, 161 applications of, 161

antibodies, 162

application of peptide arrays: miscellaneous, 228 enzyme-substrate and enzyme-inhibitor

interactions, 226 peptidomimetics, 231 protein-protein interactions, 224

assays for, 224 read-out, 219 screening, 215

generation of, 128

coherent surfaces and surface modification, 163–178

generation of micro-structured surfaces, 173 peptide array preparation, 182

techniques for array production with pre-synthesized peptides, 200

library types, 200

de novo approaches, 210

protein sequence-derived libraries, 204 Peptide arrays, 182

architectures

gel pad arrays of, 172

gold electrodes arrays of, 56–57 assays, 215

read-out, 219 screening, 215

cell binding, 300 micro-structured surfaces, 173 preparation, 173

chemoselective reactions, 196 contact printing, 61, 173, 200 non contact printing, 129, 200

pre-synthesized peptides, 200 screening 215

surface modification, 163 Peptide arrays, applications of

4 α-helix bundle mini-protein of, 217, 229 antibodies, 162

antibody paratope mapping of, 224 bibliography of, 162, 231, 265 chaperone activity, 225 characterization of peptide ligand, 229 DNA binding, 228

enzyme-inhibitor interactions, 226

INDEX

enzyme–substrate interactions, 95 linear epitopes, 222

metal ion binding peptides, 229 optimization of peptidic ligands, 229 peptide ligands, 210–211, 213

polyclonal antibody epitope mapping, 224 protein interaction domain-ligand interactions,

206

Peptide arrays, read out of, chemoluminescence, 162, 219 chromogenic, 162, 219 fluorescence, 162, 219 label-free, 162, 219 radioactivity, 130, 162, 219

Peptide libraries

split-mix synthesis method, 283–284, 289

Peptide ligands, de novo approaches for identification of, 211

combinatorial library, 231, 285 random scan, 285

Peptide microarrays, 163, 197, 199, 221, 226–228, 230

immobilization methods, 289

in situ synthesis, 185, 191, 200, 289

Peptide nucleic acids (PNAs) nucleotide analogs, 167, 190, 228

Peptide sequence,

combinatorial explosion of 210

Peptide synthesis on coherent surfaces, principle of, 186

Peptide

SPOT synthesis 162–163, 190–192 Peptide/ligand interaction, 171 Peptidomimetrics, 266

Perfect match (or PM) features, 37, 431 Periodic granular rimming flow, 350 Phage 434 binding specificity, 486 Phage, gene expression of, 478 Phage-display libraries, 128

Phil’s revised assembly program (Phrap), 376, 385

Phil’s Revised Editor (Phred), 376 Phosphorylation, 18, 173, 220–221, 227 Photo-induced graft copolymerization, 165 Photolithographic masks, 178 Photolithography for patterning of surface free

energies, 183 Photolithography techniques, 61

Photolithography, “topdown” process of, 147 Photonic crystals, 153

Photoresist coatings, 178 Photosensitizers, 165 Phrap score, 377, 386

Phrap. See Phil’s revised assembly program Phred. See Phil’s Revised Editor

INDEX

Physiometric Effects, 118 PhysioNetics, 111

PKA assay, 18–19 PKA inhibitors, 19

Plastic devices, 312, 314, 316 microfluidic devices, 311 direct fabrication, 316

laser ablation, 316 mechanical machining, 316

replication casting, 316

compression molding, 316 embossing, 316

injection molding, 316

Plastic microfluidic devices for DNA and protein analyses, 315 detection, 316

DNA analyses, 318

integrating PCR and DNA fragment separations, 318

DNA sequencing, 320

DNA sample purification, 321 materials, 312

electrokinetic pumping, 312 plastic devices, 312

device fabrication, 316 pumping and detection, 316

protein analyses, 311

enzymatic digestion for protein mapping, 324 isoelectric focusing for studying protein

interactions, 323, 326 Pneumatic pressure pumps, 312 Polarizability factor, 108, 119 Polarization, double layer, 107 Polyethylene, 162, 165, 167, 170, 284 Poly-L-Lysine, 61, 181

Poly-lysine coated glass slides, 173 Polymers, amino modified, 162

Polymers, methacrylate and acrylamide, 61 Polymorphism discrimination assays, 31 Polymorphism

restriction fragment length, 449 single strand conformational, 449

Polymorphism, melting curve single nucleotide, 449 Polypropylene, 162, 165–166

Polystyrene, 147, 165 Polyurethane films, 164

Power spectral density analysis, 68–69

Printed cDNA microarrays, methods for production of, 39

Printed oligonucleotide microarrays manufacturing of synthetic DNA, 139 pre-synthesized DNA probe, 36 synthetic oligonucleotide probes, 36

Probe-target binding, 406

Probe-target hybridization kinetic rate, 406

533

Probe-target hybridization, thermodynamic parameters of, 407

Protein analyses, 311 enzymatic digestion, 324 isoelectric, 323

Protein chip array, 298

Protein interactions, detection by ELISA-based sandwich approach, 130

surface plasmon resonance method, 130, 162, 296, 299

rolling circle amplification method, 130, 449 Protein microarrays, 127

for analysis of proteins involved in recombination & DNA repair

protein expression microarrays, 130–132 protein interaction arrays, 132–133

generation of, 128 proteins, 128 antibodies, 128–129 surface chemistry, 129

microarray production, 129 detection, 130

protein arrays,133

Protein microarrays, classification of, 127 Protein sequence-derived libraries

amino acid substitution, 206–207, 209 combinatorial deletion, 208 cyclization scans, 208

duotope scan, 204, 206 hybritope scan, 204 overlapping peptides, 204 substitutional analysis, 207–208 trancation, 208

types of, 210

Protein synthesis, localization of mRNPs in, 414 Protein-DNA interactions, 132

Protein-DNA specificity, levels of, 478 Protein-protein interactions, 224 Proteins, 128

Proteins, ARE binding, 422 Proteins, bound, detection of

grating couplers, 296

label-free optical techniques, 296 reflectometry, 296

surface plasmon resonance, 296 Proteins, fluorescence, 55

Proteomic analysis by protein array, concept of, 127 Proteomics and genomics, application of electronic

microarray technology in, 3–18 Proteomics, applications in, 18 Prothrombin, 10

Psoralen, crosslinker agent, 152 Pyrethroid sensing, 75

single neuron sensing, 75 single osteoblast sensing, 76

534

Pyrethroid, visualization of physiological changes due to effect of

on neurons, 88–91

on osteoblasts, 91, 91–93

Pyroccocus furious crystal structure, 131 Pyrrole-modified peptides, electrochemical

copolymerization of, 197

Qiagen quantiprobeTM, 27 Qiagen, 31 QuantiProbeTM, 31

Quantitative assay of specific RNA target, 29 Quantum dots, 137–140

Quantum dots, 140

Quick Spin protein desalting column, 345

RAD51B-histone interactions, 133 Reactive oxygen species, 84 Reads

misassembled, 376 overlapping, 376 shotgun, 376

Real time RT-PCR, 31

Real-time PCR, mechanism of, 32

Reciprocal chromosomal translocations, 502, 513 Recombinant his-tagged proteins, 129

Reporter dyes, wavelength shifting, 408

Resonant mirror-based biosensor (Lab Systems), 50 Restriction digest fingerprinting, 370

Restriction enzymes, 370, 478

Restriction fragment length polymorphism (RELP), 449

Reverse transcription-polymerase chain reaction (RT-PCR), 23

RFLP See Restriction fragment length polymorphism RFMF heating of nanoparticles, 469

RFMF heating of nanoparticles, determination of effective temperature by, 469

Ribozyme expression systems, 499, 515 functional analysis of genes, 497 gene therapy, 497

pol III system, 499

Ribozyme, subcellular localization of, 501 Ribozymes into cells, methods for introduction of, 506 Ribozymes

administration of, 498–499 RNA-protein hybrid, 498, 505

Ribozymes, as therapeutic agents, 515

Ribozymes, engineered, efficient tools for molecular gene therapy and gene discovery, 505

maxizymes, allosterically controllable ribozymes, 508

allosterically controllable maxizyme, design of, 509

maxizyme technology, generality of, 512

INDEX

oncogene, inactivation in mouse model, 512 hybrid ribozymes, identification of genes using,

513–514

shortened hammerhead ribozymes as dimers, 508 methods for introduction of ribozymes into cells,

497–499

ribozyme expression systems, 499 higher-order structure, and their activity,

relationship between, 149, 499 Pol III system, 499–500

subcellular localization and efficacy, 501 tRNA-ribozymes, export from nucleus to

cytoplasm, mechanism of, 504 RNA-protein hybrid ribozymes, 505

accessibility to ribozymes of their target mRNAs, 505

hybrid ribozymes that efficiently cleave their target mRNAs, 505

Ribozymes, secondary structures of, 500 Ribozymes, subcellular localization and efficacy of,

499, 501

factors affecting efficacy, 507 RMS power, 69

RNA constructs, 137

RNA detection, living cell, 411 cellular delivery of probes, 419 intracellular probe stability, 419, 424 intracellular RNA detection, 434

RNA polymerase T7, mediated amplification of, 12, 38

RNA processing, RNases roles in, 412–413 RNA protection, 23

RNA study

ABI Prism 7900HT SDS, 32 analytical sensitivity, 33

limit of detection (LOD), 34 limit of quantitation (LOQ), 34

bias percentage 33

RNA targets, intracellular, 411

RNA viral load tests testing, TaqMan hydrolysis probes in, 29

RNA, secondary structure of, 418

RNA: DNA duplexes, detection of, 37–38 RNAm localization in nucleus, 413–414 RNAm, splicing of, 412–413 RNA-protein hybrid ribozymes, 505

RNAs, functional, in cultured cells, activities of, 511 Rolling circle amplification (RCA), 130, 449 RRNA pre-transcripts, degradation of, 426

Saccharomeyces cerevisiae, proteome of, 128 SBFI, AM ester of

Scanning force microscopy, to study DNA flexibility, 484

ScorpionTM Primer/Probes, 26, 30

INDEX

Screen-sequence-screen-sequence approach for clone cluster, 370

Secondary ion mass spectroscopy, 163 Sensitizers, 165

Separation buffer, 65, 68

Sequence data, hierarchical approach of assembly, reconstructing sequences, 373 finishing, filling gaps of, 367, 378 mapping, source clone, 378

sequencing, raw data, 366–367

Sequence dependent elasticity, experimental consequences of, 486

Sequence dependent

aspects to double helix elastic constants, 484 bending of double helix

structure atlas of DNA, 485

Sequence-ready clones, retrieving from clone library, 369

Sequencing by hybridization, 382 Sequencing human genome, approaches in

construction of chromosome tiling paths, 385 data sharing, 385

Sequencing of human genome, large-scale, research network for, 389

Sequencing source clones, methodological challenges, 381

Sequencing source clones, strategy used for, 368, 381–382, 386, 388

Sequencing technologies, revolutionary, 382 Sequencing, 382

Serial analysis of gene expression (SAGE), 23, 403 Short tandem repeat (STR) forensics analysis, 137 Short tandem repeats (STRs), 10

Short tandem repeats, 10

Shotgun sequence reads generation from source clone, generic procedures for

base-calling, 374, 378, 382 data curation, 374 detection, 374 fragmentation, 372 sequencing, 372

size selection, 373

source clone DNA preparation, 372 subcloning, 373

template DNA preparation, 373

Shotgun sequencing of gene, 372–373, 375, 381–383, 386

Shotgun sequencing, basic framework of level of redundancy, 383

read length, 372

robots for DNA template preparation, 385 sequencing reactions, 368, 373

template, 383

Signal processing, 60, 68–69

Signature pattern for single osteoblast, 75

535

Signature pattern vector (SP), 69 Signature pattern vector (SPV) of cell, 70

Signature patterns of cell based biosensors, 52 Signature patterns of specific chemical agent, 52, 60 Signature Patterns, 47, 52, 60, 65, 98

Silicon wafers, transformation into mercapto-modified surfaces, 197

Silicon, oxidized, 170

Single fluorophore experimental design, 38 Single nucleotide polymophisms (SNPs), 10 Single nucleotide polymorphism, 405, 409, 412 Single nucleotide polymorphisms (SNPs), 23, 448

Single platinum micro-electrode pad on the NanoChip rmicroarray, 6

Single strand conformational polymorphism (SSCP), 449 SNP discovery, 448

SNP genotyping analysis, 145 SNP genotyping, 30

SNP identification technique, 449

SNP. See Single nucleotide polymophisms, 10 SNP-IT, robotic version of, 449

SNPs, diseases associated with, 10, 447 SODA. See synthesis on defined areas

Soman and VX (GD), chemical warfare agents, 57 Source clone DNA preparation, 372, 374

Source clone, gaps of, 393 Source clones acquisition, 368 Source clones

strategies for mapping of

clone insert end sequencing, 370 FISH, 370, 372, 378

library screening, 286, 369–371 restriction digest fingerprinting, 370–371

Spearman rank correlation coefficient, 42–43 SPOT concept, application of, 189

SPOT synthesis, 167

SPOT synthesis, 162, 167, 189–190, 210, 214, 219, 222–223, 225–227, 230–231, 298

SPOT. See spot synthesis of peptides SSCP. See Single strand conformational

polymorphism

Stacked microlaboratory, fabrication of stacked structure, 15–16

Stainless steel foils, 171

Stainless steel foils, functionalization of, 171 Staphylococcus enterotoxin a (SEA) and b (SEB), 14,

17

Starbust dendrimer coating, 179 Stem cells

DEP spectrum of, 116, 122 DEP behavior of, 113–116

Stem sequences, 30 fluorescent PCR primers, 30

hairpin loop probe structure, 30 SNP genotyping, 30, 145