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Molecular Diagnostics - Technologies, Markets and Companies

리서치사 Jain Pharmabiotech
발행일 2012년 04월 상품코드 70915
페이지 정보
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US $ 5,500 ￦ 6,553,200 PDF BY E-mail (Single Site License)


영문목차

Abstract

Benefits of this report

  • This report has evolved during the past 17 years, profiting from feedback by numerous readers and experts.
  • The most comprehensive and up-to-date one-stop source of information on technical and commercial aspects of molecular diagnostics.
  • Includes profiles of 317 companies, the largest number in any report on this topic.
  • 500 references, cited in the report are included in the bibliography.
  • The text is supplemented by 98 tables and 15 figures.

Who should read this report?

  • Chief executive officers of molecular diagnostic companies.
  • Business development executives of pharmaceutical and biotechnology companies.
  • Executives of companies involved in developing integration of diagnosis and treatment as well as those interested in personalized medicine.
  • Officers of genomic and proteomic companies interested in diagnostic technologies.
  • Research scientists involved in application of molecular diagnostic technologies.
  • Planners of healthcare services.

Summary

This report describes and evaluates the molecular diagnostics technologies that will play an important role in practice of medicine, public health, pharmaceutical industry, forensics and biological warfare in the 21st century. This includes several polymerase chain reaction (PCR)-based technologies, fluorescent in situ hybridization (FISH), peptide nucleic acids (PNA), electrochemical detection of DNA, mitochondrial DNA, biochips, nanotechnology and proteomic technologies.

Initial applications of molecular diagnostics were mostly for infections but are now increasing in the areas of genetic disorders, preimplantation screening and cancer. Genetic screening tests, despite some restrictions is a promising area for future expansion of in vitro diagnostic market. Molecular diagnostics is being combined with therapeutics and forms an important component of integrated healthcare. Molecular diagnostic technologies are also involved in development of personalized medicine based on pharmacogenetics and pharmacogenomics. Currently, there has been a considerable interest in developing rapid diagnostic methods for for point-of-care and biowarfare agents such as anthrax.

The number of companies involved in molecular diagnostics has increased remarkably during the past few years. More than 500 companies have been identified to be involved in developing molecular diagnostics and 317 of these are profiled in the report along with tabulation of 725 collaborations. Despite the strict regulation, most of the development in molecular diagnostics has taken place in the United States, which has the largest number of companies.

The markets for molecular diagnostics technologies are difficult to estimate. Molecular diagnostics markets overlap with markets for non-molecular diagnostic technologies in the in vitro diagnostic market and are less well defined than those for pharmaceuticals. Molecular diagnostic markets are analyzed for 2011 according to technologies, applications and geographical regions. Forecasts are made up to 2021. A major portion of the molecular diagnostic market can be attributed to advances in genomics and proteomics. Biochip and nanobiotechnology are expected to make a significant contribution to the growth of molecular diagnostics.

This report was first published as DNA Diagnostics in 1995 by PJB Publications, UK. It was updated in 1997 as Molecular Diagnostics and the next edition, Molecular Diagnostics II, was published by Decision Resources Inc in 1999. All the three versions of the reports were well accepted and sold widely.The report has been rewritten several times since then.

Table of Contents

Part I

0. Executive Summary 24

1. Introduction 26

  • Definitions and scope of the subject 26
  • Historical evolution of molecular diagnostics 26
  • Molecular biology relevant to molecular diagnostics 27
  • DNA 27
  • DNA polymerases 27
  • Restriction endonucleases 28
  • DNA methylation 28
  • RNA 29
  • RNA polymerases 29
  • Non-coding RNAs 29
  • DNA transcription 30
  • Chromosomes 30
  • Telomeres 31
  • Mitochondrial DNA 31
  • Genes 32
  • The genetic code 32
  • Gene expression 32
  • The human genome 33
  • Variations in the human genome 33
  • Variations in DNA sequences 33
  • Single nucleotide polymorphisms 34
  • Haplotyping 34
  • Copy number variations in the human genome 35
  • Genotype and haplotypes 36
  • Insertions and deletions in the human genome 36
  • Complex chromosomal rearrangements 37
  • Large scale variation in human genome 37
  • Structural variations in the human genome 38
  • Replication of the DNA helix 38
  • Transposons 39
  • Proteins 39
  • Proteomics 39
  • Monoclonal antibodies 40
  • Aptamers 40
  • Basics of molecular diagnostics 40
  • Tracking DNA: the Southern blot 40
  • Pulsed-field gel electrophoresis 41
  • DNA Probes 41
  • The polymerase chain reaction 42
  • Basic Principles of PCR 42
  • Target selection 42
  • Detection of amplified DNA 42
  • Impact of human genome project on molecular diagnostics 43
  • Mapping and sequencing of structural variation from human genomes 44
  • 1000 Genomes Project 44
  • Human Variome Project 45
  • Role of bioinformatics in molecular diagnostics 46
  • Systems biology approach to molecular diagnostics 46
  • Biomarkers 46
  • Applications of molecular diagnostics 47

2. Molecular Diagnostic Technologies 50

  • Introduction 50
  • DNA sample collection and extraction 50
  • Blood samples 50
  • Dried blood spots 50
  • Buccal swabs and saliva 51
  • Urine samples for transrenal DNA 51
  • Manual vs automated DNA extraction 52
  • Sample preparation 52
  • Pressure Cycling Technology 52
  • Membrane immobilization of nucleic acids 52
  • Automation of sample preparation in molecular diagnostics 53
  • ABI PRISM 6700 Automated Nucleic Acid Workstation 53
  • BioRobot technology 53
  • COBAS AmpliPrep System 54
  • GENESIS FE500 Workcell 54
  • GeneMole 54
  • PCR BioCube 54
  • QIAsymphony 55
  • Tigris instrument system 55
  • Techniques for sample preparation that are suitable for automation 55
  • Xtra Amp Genomic DNA Extraction 55
  • Extraction of DNA from paraffin sections 55
  • Dynabead technology 56
  • SamPrep 56
  • Use of magnetic particles for automation in genome analysis 56
  • Companies involved in nucleic acid isolation 57
  • Labeling and detection of nucleic acids 58
  • Novel PCR methods 58
  • Addressing limitations of PCR 58
  • CAST-PCR 59
  • Combined PCR-ELISA 59
  • Convection PCR 59
  • Digital PCR 60
  • Emulsion PCR 61
  • ExCyto PCR 61
  • Long and accurate PCR 61
  • Multiplex PCR 61
  • Overlap extension PCR 62
  • Real-time PCR systems 62
  • Dyes used in real-time PCR 63
  • Commercially available real-time PCR systems 63
  • LightCycler PCR system 64
  • LightUp probes based on real-time PCR 64
  • READ™ real-time PCR method 65
  • StellARray™ technology 65
  • 7500 Fast Dx Real-Time PCR Instrument 65
  • Applications of real-time PCR 65
  • Limitations of real-time PCR 66
  • Quantitative PCR for accurate low level DNA analysis 66
  • qPCR for quantification of circulating mtDNA 67
  • Guidelines for real-time qPCR 67
  • Future applications of real-time qPCR 67
  • Reverse transcriptase (RT)-PCR 68
  • Standardized reverse transcriptase PCR 69
  • Single cell PCR 69
  • LATE-PCR 69
  • COLD-PCR 69
  • AmpliGrid-System 70
  • DNA melt analysis 71
  • High-resolution DNA melt analysis for genotyping 71
  • PCR device for DNA melt analysis in space 71
  • Monitoring of gene amplification in molecular diagnostics 71
  • Non-PCR nucleic acid amplification methods 72
  • DNA probes with conjugated minor groove binder 72
  • Dynamic Flux Amplification 72
  • Isothermal reaction for amplification of oligonucleotides 72
  • ICAN (Isothermal and Chimeric primer-initiated Amplification of Nucleic Acids) 73
  • Linked Linear Amplification 73
  • Multiplex Ligation-Dependent Probe Amplification 73
  • Rapid analysis of gene expression 74
  • Rolling circle amplification technology 74
  • Gene-based diagnostics through RCAT 76
  • RCAT-immunodiagnostics 76
  • RCAT-pharmacogenomics 76
  • Circle-to-circle amplification 77
  • Ramification amplification method 77
  • Single Primer Isothermal Amplification 77
  • Transcription mediated amplification 78
  • WAVE nucleic acid fragment analysis system 78
  • Technologies for signal amplification 79
  • 3 DNA dendrimer signal amplification 79
  • Hybridization signal amplification method 80
  • Signal mediated amplification of RNA technology 81
  • Invader assays 81
  • Hybrid Capture technology 83
  • Branched DNA test 83
  • Tyramide signal amplification 84
  • Non-enzymatic signal amplification technologies 84
  • Direct molecular analysis without amplification 85
  • Trilogy™ Platform 85
  • Direct detection of dsDNA 86
  • Multiplex assays 86
  • Fluorescent in situ hybridization 86
  • FISH technique 87
  • Applications of FISH 88
  • Modifications of FISH 88
  • Direct visual in situ hybridization 89
  • Direct labeled Satellite FISH probes 89
  • Comparative genomic hybridization 89
  • Primed in situ labeling 89
  • Interphase FISH 90
  • FISH with telomere-specific probes 90
  • Multicolor FISH 91
  • Simultaneous Ultrasensitive Subpopulation staining/Hybridization In situ 91
  • Automation of FISH 91
  • Companies involved in FISH diagnostics 91
  • RNA diagnostics 92
  • RNA isolation from tissue samples 92
  • Commercially available tests for mRNA detection and quantitation 93
  • Branched-chain DNA assay for measurement of RNA 94
  • Cycling probe technology 94
  • Invader RNA assays 94
  • Linear RNA amplification 95
  • Non-isotopic RNase cleavage assay 95
  • Nucleic acid sequence-based amplification 95
  • Q Beta replicase system 97
  • RNAScope 97
  • RNA expression profiling 98
  • Visualization of mRNA expression in vivo 98
  • Solid Phase Transcription Chain Reaction 98
  • Transcriptome analysis 98
  • MicroRNA diagnostics 99
  • Real-time PCR for expression profiling of miRNAs 99
  • Microarray vs quantitative PCR for measuring miRNAs 100
  • Use of LNA to explore miRNA 100
  • Nuclease Protection Assay to measure miRNA expression 100
  • Microarrays for analysis of miRNA gene expression 101
  • Modification of in situ hybridization for detection of miRNAs 101
  • Whole genome amplification 102
  • Companies that provide technologies for whole genome amplification 102
  • QIAGEN's Repli-G system 103
  • GenomePlex™ Whole Genome Amplification 103
  • DNA sequencing 103
  • Companies involved in sequencing 105
  • Applications of next generation sequencing in molecular diagnostics 107
  • Companies developing sequencing for molecular diagnostics 107
  • Genome-wide approach for chromatin mapping 108
  • Mitochondrial sequencing 109
  • Identification of unknown DNA sequences 109
  • Optical mapping 109
  • Gene expression analysis 110
  • Gene expression profiling on whole blood samples 111
  • Gene expression patterns of white blood cells 111
  • Gene expression profiling based on alternative RNA splicing 111
  • MAUI (MicroArray User Interface) hybridization 112
  • Monitoring in vivo gene expression by molecular imaging 112
  • Serial analysis of gene expression (SAGE) 112
  • Single-cell gene expression analysis 113
  • T cell receptor expression analysis 114
  • Tangerine™ expression profiling 114
  • Whole genome expression array 114
  • Ziplex™ system 115
  • Companies involved in gene expression analysis 115
  • Peptide nucleic acid technology 116
  • Use of PNA with fluorescence in situ hybridization 117
  • PNA and PCR 117
  • Use of PNA with biosensors 118
  • PNA-based PD-loop technology 118
  • PNA-DNA hybrid quadruplexes 119
  • Companies involved in PNA diagnostics 119
  • Locked nucleic acids 119
  • Zip Nucleic Acids 120
  • Electrochemical detection of DNA 121
  • Mediated nucleic acid oxidation 121
  • Detection of hybridized nucleic acid with cyclic voltametry 122
  • Electrochemical detection based on Toshiba's CMOS technology 122
  • Concluding remarks on electrochemical DNA detection 122
  • Bead-based assay platforms 122
  • Scorpions™ technology 123
  • The Scorpions reaction 123
  • Applications of Scorpions 124
  • Nucleic acid lateral flow molecular diagnostics 124
  • Omics-based tests 125

3. Biochips, Biosensors, and Nanobiotechnology 126

  • Introduction to biochip technology 126
  • Applications of biochips in diagnostics 126
  • GeneChip 127
  • GeneChip Human Genome Arrays 128
  • AmpliChip CYP450 128
  • Electronic detection of nucleic acids on microarrays 128
  • Microchip capillary electrophoresis 129
  • Strand displacement amplification on a biochip 129
  • Rolling circle amplification on microarrays 129
  • LiquiChip-RCAT 129
  • Fast PCR biochip 130
  • Multiplex microarray-enhanced PCR for DNA analysis 130
  • Multiplexed Molecular Profiling 130
  • Universal DNA microarray combining PCR and ligase detection reaction 131
  • Genomewide association scans 131
  • Whole genome chips/microarrays 132
  • Transposon insertion site profiling chip 132
  • Standardizing the microarrays 133
  • Companies involved in developing biochip technology for diagnostics 133
  • Future of biochip technology for molecular diagnostics 134
  • Microfluidic chips 135
  • Fish-on-chip 135
  • Lab-on-a-chip 135
  • LabCD 136
  • Micronics' microfluidic technology 136
  • Microfluidic chips/arrays using PCR 136
  • Microfluidic automated DNA analysis using PCR 136
  • Digital PCR Array 136
  • Digital PCR on a SlipChip 137
  • Microfluidic chips integrated with RCAT 137
  • Microfluidic chips integrated with PET 137
  • Companies developing microfluidic technologies 138
  • Biosensor technologies 138
  • Classification of biosensor technologies 139
  • DNA-based biosensors 140
  • DNA hybridization biosensor chips 140
  • PCR-free DNA biosensor 140
  • DNA based biosensor to detects metallic ions 141
  • Genetically engineered B lymphocytes 141
  • Biosensors immunoassays 141
  • PNA (peptide nucleic acid)-based biosensors 142
  • Protein-based biosensors 142
  • Antibody biosensors 142
  • Cell-based biosensors (cytosensors) 142
  • Multicell biosensors 143
  • Microbial biosensors 143
  • Optical biosensors 144
  • Surface plasmon resonance technology 144
  • Label-free optical biosensor 145
  • Microsensors using with nano/microelectronic communications technology 145
  • Electrochemical sensors 145
  • Enzyme electrodes for biosensing 145
  • Conductometric sensors 146
  • Electrochemical genosensors 146
  • Electrochemical nanobiosensor 146
  • Bioelectronic sensors 147
  • Phototransistor biochip biosensor 147
  • Ribozyme-based sensors 147
  • RiboReporters 148
  • Concluding remarks and future prospects of biosensor technology 148
  • Companies developing biosensors for molecular diagnostics 149
  • Molecular labels and detection 150
  • Detection technologies for molecular labels 151
  • Fluorescence and chemiluminescence 151
  • Fluorescence technologies for label detection 152
  • Companies with fluorescence and chemiluminescence products 152
  • Molecular beacons 153
  • The Green fluorescent protein 154
  • Multiophoton detection radioimmunoassay 155
  • Multi-pixel photon counter 155
  • Enzyme labels and detection by fluorescence 155
  • Phase-sensitive flow cytometry 156
  • Microtransponder-based DNA diagnostics 156
  • Laboratory Multiple Analyte Profile 157
  • Multiple labels 157
  • Protein-DNA chimeras for detection of small numbers of molecules 158
  • Single molecule detection 158
  • Atomic force microscopy 159
  • Capillary electrophoresis 159
  • Confocal laser scanning 159
  • nCounter Analysis System 159
  • Spectrally resolved fluorescence lifetime imaging microscopy 160
  • Molecular imaging 160
  • Technologies for molecular imaging 160
  • Basic research in molecular imaging 161
  • Devices for molecular imaging 162
  • Molecular imaging in clinical practice 162
  • Challenges and future prospects of molecular imaging 162
  • Companies involved in molecular imaging 162
  • Nanobiotechnology for molecular diagnostics 163
  • Magnetic nanoparticles 164
  • Gold nanoparticles 165
  • Quantum dot technology 165
  • Nanotechnology on a chip 166
  • Nanogen's NanoChip 167
  • Fullerene photodetectors for chemiluminescence detection on microfluidic chip 167
  • Diagnostics based on nanopore technology 167
  • Nanosensors 168
  • Detection of cocaine molecules by nanoparticle-labeled aptasensors 168
  • Nanosensors for glucose monitoring 168
  • PEBBLE nanosensors 169
  • Quartz nanobalance biosensor 169
  • Cantilever arrays 169
  • Resonance Light Scattering technology 170
  • DNA nanomachines for molecular diagnostics 170
  • Nanobarcodes technology for molecular diagnostics 171
  • Qdot nanobarcode for multiplexed gene expression profiling 171
  • Role of nanobiotechnology in improving molecular diagnostics 171
  • Companies involved in nanomolecular diagnostics 172
  • Concluding remarks about nanodiagnostics 174
  • Future prospects of nanodiagnostics 175

4. Proteomic Technologies for Molecular Diagnostics 176

  • Introduction 176
  • Proteomic technologies 176
  • Biomarkers of disease 176
  • Proteomic tools for biomarkers 176
  • Search for biomarkers in body fluids 177
  • Captamers with proximity extension assay for proteins 177
  • Cyclical amplification of proteins 177
  • Detection of misfolded proteins by ELISA with exponential signal amplification 178
  • Detection of proteins by Western blot 178
  • Diagnostics based on designed repeat proteins 178
  • Differential Peptide Display 179
  • Light-switching excimer probes 179
  • MALDI-TOF MS 180
  • Molecular beacon aptamer 180
  • Molecular beacon assay 181
  • Proteomic patterns 181
  • Real-time PCR for protein quantification 182
  • Protein biochip technologies 182
  • ProteinChip 183
  • LabChip for protein analysis 184
  • TRINECTIN proteome chip 184
  • Protein chips for antigen-antibody interactions molecular diagnostics 184
  • Microfluidic devices for proteomics-based diagnostics 185
  • Nanotechnology-based protein biochips/microarrays 185
  • Nanoparticle protein chip 185
  • Protein nanobiochip 185
  • Protein biochips based on fluorescence planar wave guide technology 186
  • New developments in protein chips/microarrays 186
  • Antibody microarrays 187
  • Aptamer-based protein biochip 187
  • Multiplexed Protein Profiling on Microarrays 187
  • Proteomic pattern analysis 188
  • Single molecule array 188
  • Viral protein chip 188
  • Commercial development of protein chips for molecular diagnostics 189
  • Proteome Identification Kit 190
  • Laser capture microdissection (LCM) 190
  • LCM technology 190
  • Applications of LCM in molecular diagnostics 191
  • Proteomic diagnosis of CNS disorders 191
  • Cerebrospinal fluids tests based on proteomics 191
  • Urine tests for CNS disorders based on proteins in urine 192
  • Diagnosis of CNS disorders by examination of proteins in the blood 193
  • Diagnosis of CNS disorders by examination of proteins in tears 193
  • Role of proteomics in the diagnosis of Alzheimer's disease 194
  • Role of proteomics in the diagnosis of Creutzfeldt-Jakob disease 194
  • Future prospects of use of proteomics for diagnosis of CNS disorders 194
  • Concluding remarks on the use of proteomics in diagnostics 195

5. Molecular Diagnosis of Genetic Disorders 196

  • Introduction 196
  • Cytogenetics 197
  • FISH with probes to the telomeres 197
  • Single copy FISH probes 197
  • Comparative genomic hybridization 198
  • Use of biochips in genetic disorders 198
  • Representational oligonucleotide microarray analysis 199
  • SignatureChipR-based diagnostics for cytogenetic abnormalities 199
  • Diagnosis of genomic rearrangements by multiplex PCR 199
  • Quantitative fluorescent PCR 199
  • Mutation detection technologies 200
  • PCR-based methods for mutation detection 201
  • Cleavase Fragment Length Polymorphism 201
  • Direct dideoxy DNA sequencing 201
  • Digital Genetic Analysis (DGA) 201
  • Fluorescence-based directed termination PCR 202
  • Fluorescence melting curve analysis for multiplex mutation detection 202
  • Heteroduplex analysis 203
  • Restriction fragment length polymorphism 203
  • Single-stranded conformation polymorphism (SSCP) analysis 203
  • TaqMan real-time PCR 204
  • Non-PCR methods for mutation detection 204
  • Arrayed primer extension 204
  • BEAMing (beads, emulsion, amplification, and magnetics) 205
  • ELISA-protein truncation test 205
  • Enzymatic mutation detection 205
  • Specific anchor nucleotide incorporation 206
  • Conversion analysis for mutation detection 206
  • Biochip technologies for mutation detection 206
  • Combination of FISH and gene chips 207
  • Haplotype Specific Extraction 207
  • Use of biosensors for detection of mutations 207
  • Technologies for SNP analysis 208
  • DNA sequencing 209
  • Electrochemical DNA probes 209
  • Use of NanoChip for detection of SNPs 210
  • Single base extension-tag array 210
  • Laboratory Multiple Analyte Profile 210
  • SNP genotyping with gold nanoparticle probes 211
  • PCR-CTPP (confronting two-pair primers) 211
  • Peptide nucleic acid probes for SNP detection 211
  • SNP genotyping on a genome-wide amplified DOP-PCR template 211
  • Pyrosequencing 212
  • Reversed enzyme activity DNA interrogation test 212
  • Smart amplification process version 2 213
  • Zinc finger proteins 213
  • UCAN method (Takara Biomedical) 213
  • Biochip and microarray-based detection of SNPs 214
  • SNP genotyping by MassARRAY 214
  • Electronic dot blot assay 214
  • Biochip combining BeadArray and ZipCode technologies 215
  • SNP-IT primer-extension technology 215
  • OmniScan SNP genotyping 215
  • Affymetrix SNP genotyping array 215
  • Concluding remarks on SNP genotyping 216
  • Limitations of SNP in genetic testing 216
  • Haplotyping versus SNP genotyping 217
  • Nanofluidics technology for high throughput SNP genotyping 217
  • Companies involved in developing technologies/products for SNP analysis 217
  • Role of copy number variations in genetic diagnostic testing 219
  • CNVs in various diseases 219
  • CNVs in genetic epilepsy syndromes 219
  • CNVs associated with schizophrenia 219
  • Methods for determination of CNVs 220
  • Digital array for CNV detection 220
  • Wellcome Trust Case Control Consortium CNV typing array 220
  • CNVer algorithm for CNV detection 220
  • Study of rare variants in pinpointing disease-causing genes 221
  • Prenatal DNA diagnosis 222
  • Invasive prenatal diagnostic procedures 222
  • Amniocentesis 222
  • Chorionic villus sampling 222
  • Molecular methods for prenatal diagnosis 222
  • aCGH for prenatal diagnosis 222
  • BAC HD Scan test 223
  • FISH for prenatal diagnosis 223
  • PCR for prenatal diagnosis 223
  • In vivo gene expression analysis of the living human fetus 224
  • Non-invasive prenatal molecular diagnostic procedures 224
  • Fetal cells separation from maternal blood for genetic diagnosis 224
  • Digital relative mutation dosage in maternal plasma 224
  • Prenatal testing based on transrenal DNA from urine 225
  • Tests on fetal DNA in maternal blood 225
  • Sequencing-based methods for prenatal diagnosis from maternal DNA 225
  • Directed DNA analysis of maternal blood 226
  • Applications of prenatal diagnosis 227
  • Antenatal screening for Down's syndrome 228
  • Diagnosis of congenital infections 228
  • Diagnosis of eclampsia 229
  • Preimplantation genetic diagnosis 229
  • Technologies for preimplantation genetic diagnosis (PGD) 229
  • PCR for preimplantation genetic diagnosis 229
  • FISH for preimplantation genetic diagnosis 230
  • Microarrays for preimplantation genetic diagnosis 230
  • Conditions detected by preimplantation genetic diagnosis 231
  • The future of preimplantation genetic diagnosis 231
  • Companies involved in prenatal/preimplantation diagnosis 232
  • Cystic fibrosis 233
  • Detection of CFTR gene mutations 233
  • CFTR technologies of various companies 234
  • Genzyme's CF gene sequencing 234
  • CF Plus™ Tag-It Cystic Fibrosis Kit 235
  • Asuragen's bead array test 235
  • The Ambry CF Test 236
  • Biochip for CF diagnosis 236
  • Identification of CF variants by PCR/Oligonucleotide Ligation Assay 236
  • SensiGene (SEQUENOM) CF carrier screening test 236
  • Serum proteomic signature for CF using antibody microarrays 237
  • Guidelines for genetic screening for CF 237
  • Congenital adrenal hyperplasia 237
  • Primary immunodeficiencies 238
  • Hematological disorders 239
  • Hemoglobinopathies 239
  • Sickle cell anemia 239
  • Thalassemia 240
  • Paroxysmal nocturnal hemoglobinuria 240
  • Hemophilia 240
  • Hereditary hemochromatosis 240
  • Polycystic kidney disease 241
  • Hereditary metabolic disorders 241
  • Lesch-Nyhan Syndrome 241
  • Gaucher's Disease 242
  • Acute Intermittent Porphyria 242
  • Phenylketonuria 242
  • Hereditary periodic fever 243
  • Achondroplasia 243
  • Molecular diagnosis of eye diseases 243
  • Molecular diagnosis of retinitis pigmentosa 243
  • Genetic screening for glaucoma 244
  • Role of molecular diagnostics in rheumatoid arthritis 244
  • Molecular diagnosis of neurogenetic disorders 245
  • Alzheimer's disease 246
  • Autism spectrum disorders 247
  • CNVs associated with autism 247
  • Charcot-Marie Tooth disease 248
  • Down syndrome 248
  • Duchenne and Becker muscular dystrophy 249
  • eNOS gene polymorphisms as predictor of cerebral aneurysm rupture 250
  • Fragile X syndrome 250
  • Huntington disease 250
  • Hereditary neuropathy with liability to pressure palsies 251
  • Mitochondrial disorders affecting the nervous system 251
  • Parkinson's disease 252
  • Pompe's disease 253
  • Spinal muscular atrophy 253
  • Triple repeat disorders 253
  • Genetic testing for disease predisposition 254
  • Direct-to-consumer genetic tests 254

6. Molecular diagnosis of cardiovascular disorders 256

  • Introduction 256
  • Coronary heart disease 257
  • Genomics of coronary heart disease 257
  • Cardiomyopathy 258
  • Familial Hypertrophic Cardiomyopathy 258
  • Idiopathic dilated cardiomyopathy 258
  • Cardiac Arrhythmias 258
  • Long Q-T Syndrome 258
  • Familial atrial fibrillation 259
  • Idiopathic ventricular fibrillation 259
  • Congestive heart failure 259
  • Hypertension 260
  • Disturbances of blood lipids 260
  • Familial dyslipoproteinemias 260
  • Hypercholesterolemia 260
  • Thrombotic disorders 261
  • Factor V Leiden mutation 261
  • Pulmonary embolism 262
  • Hereditary thrombophilia 262
  • Molecular diagnostics for monitoring heart transplant rejection 262
  • AlloMapR molecular expression testing 262
  • Commercial molecular diagnostics for cardiovascular disorders 263

7. Molecular Diagnosis of Infections 264

  • Introduction 264
  • Molecular techniques for the diagnosis of infections 264
  • Antibody-enhanced microplate hybridization assays 265
  • Bacteriophage-based methods for detection of bacteria 265
  • Biochips/microarrays for detection of microorganisms 266
  • Lawrence Livermore Microbial Detection Array 266
  • Biosensors for detection of microorganisms 266
  • Ibis T5000™ Biosensor System 266
  • DNA enzyme immunoassay 266
  • DNA biochip/microarray in diagnosis of infections 267
  • DNA-based typing methods 268
  • Restriction fragment length polymorphism analysis 268
  • Ribotyping 269
  • Random amplified polymorphic DNA 269
  • Combinatorial DNA melting assay 269
  • Electrochemical detection of pathogens 269
  • FISH for detection of infections 270
  • Helicase-dependent isothermal amplification for rapid detection of pathogens 270
  • High resolution melt analysis for diagnosis of infections 270
  • Ligase chain reaction 270
  • Mass spectrometry for microbial identification 271
  • Metagenomic pyrosequencing 271
  • Multiplex PCR for detection of infections 272
  • Dual priming oligonucleotide for multiplex PCR 273
  • LightCyclerR SeptiFast Test 273
  • Multiplex amplified nominal tandem repeat analysis 274
  • VYOOR Sepsis Test 274
  • NanoDx™ 274
  • NASBA for detection of microorganisms 274
  • Nucleic acid probes 275
  • Neutrophil CD11b expression as a diagnostic marker 275
  • Optical Mapping 275
  • PNA-FISH for diagnosis of infections 276
  • QuantiFERONR technology for pre-molecular diagnosis of infections 276
  • Quantitative reverse-transcription PCR for bacterial diagnostics 277
  • Rupture event scanning 277
  • Real-time single-molecule imaging of virus particles 277
  • Single-strand conformational polymorphism 277
  • SmartGene platform for identifying pathogens based on genetic sequences 277
  • Tessera array technology 278
  • Unyvero Solution 278
  • Applications, advantages and limitations of molecular diagnostics 278
  • Molecular diagnostics versus other microbial detection technologies 278
  • Advantages of nucleic acid-based diagnostics in infections 279
  • Drawbacks of nucleic acid-based diagnostics in infections 279
  • Nanotechnology for detection of infectious agents 280
  • Bacterial infections 280
  • Mycobacterium tuberculosis 281
  • Conventional diagnosis of tuberculosis 282
  • Microscopic Observation Drug Susceptible Assay for tuberculosis 282
  • Molecular diagnostics for tuberculosis 282
  • Combined tuberculin testing and ELISpotPLUS assay 284
  • Biomarker-based tests for tuberculosis 284
  • Diagnosis of TB in a POC setting 285
  • Diagnosis of drug-resistant MTB infection 285
  • Xpert MTB/RIF automated molecular test for MTB 286
  • Diagnosis of other mycobacteria 286
  • Chlamydial infections 287
  • Neisseria gonorrhoeae 288
  • Bacteria associated with bacterial vaginosis 288
  • Streptococcal infections 289
  • Group B Streptococci 289
  • Streptococcus pyogenes and Streptococcus dysgalactiae 289
  • Pseudomonas aeruginosa 290
  • Helicobacter pylori 290
  • Lyme disease 290
  • Mycoplasmas 291
  • Fungal infections 292
  • PCR-based tests for fungal infections 292
  • DNA barcode marker for fungi 293
  • DNA sequencing for fungal infections 293
  • MALDI-TOF MS for diagnosis of fungal infections 293
  • Aspergillus 294
  • Candida species 294
  • Viral infections 295
  • HIV/AIDS 296
  • Diagnosis of HIV 296
  • Detection of HIV provirus 297
  • Global Surveillance of HIV-1 genetic variations 297
  • Genotyping for drug-resistance in HIV 297
  • Neonatal screening of infants of HIV-positive mothers 298
  • Phenotyping as predictor of drug susceptibility/resistance in HIV 299
  • Point-of-care testing for HIV 299
  • Resolution of indeterminate Western blot 300
  • Screening of cadaveric tissue donors 300
  • Tests used for quantification of HIV 300
  • Conclusions about HIV diagnostics 301
  • Hepatitis viruses 302
  • Hepatitis A virus 302
  • Hepatitis B virus 302
  • Hepatitis C virus 303
  • Detection and quantification of HCV RNA 303
  • Quantification of HCV RNA levels as a guide to antiviral therapy 304
  • Electrochemical DNA chip for diagnosis of HCV 304
  • HCV Genotyping as a guide to therapy 304
  • Enteroviruses 305
  • Adenoviruses 306
  • Rhinoviruses 306
  • Herpes viruses 306
  • Herpes simplex virus 306
  • Genital and neonatal herpes simplex 307
  • Human cytomegalovirus infections 307
  • Epstein-Barr virus 308
  • Human papilloma virus 308
  • Molecular diagnostics for HPV 308
  • Detection of encephalitis viruses 309
  • West Nile and St. Louis encephalitis 309
  • Venezuelan equine encephalitis virus 310
  • Detection of noroviruses 310
  • Protozoal infections 310
  • Amebiasis 310
  • Cryptosporidium parvum 311
  • Leishmaniasis 311
  • Malaria 311
  • Neurocysticercosis 312
  • Pneumocystis carinii 312
  • Toxoplasmosis 312
  • Infections of various systems 313
  • CNS infections 313
  • Molecular diagnosis in bacterial meningitis 313
  • Molecular diagnosis in herpes simplex encephalitis 313
  • Diagnosis of transmissible spongiform encephalopathies 314
  • Molecular diagnosis of respiratory viruses 315
  • SARS-associated coronavirus 315
  • Influenza viruses 316
  • Avian influenza 318
  • H1N1 influenza 322
  • Gastrointestinal infections 324
  • Periodontal infections 325
  • Diagnosis of urinary infections by a biosensor 326
  • Role of molecular diagnostics in septicemia 326
  • Limitations and needs of diagnostics for infections 327
  • Differentiation between live and antibiotic-killed bacteria 328
  • Cell-based methods for identifying pathogenic microorganisms 328
  • Cell-based virus assays 328
  • Cell-based detection of host response to infection 328
  • Role of molecular diagnostics in hospital acquired infections 329
  • Detection of hospital-acquired bacterial infections 329
  • Detection of methicillin-resistant S. aureus 329
  • Detection of vancomycin-resistant enterococci 330
  • Detection of hospital-acquired C. difficile 330
  • Bacterial genome sequencing in antimicrobial resistance 331
  • Detection of hospital-acquired viral infections 332
  • Molecular diagnosis of BK virus 332
  • Diagnosis of hospital-acquired rotavirus gastroenteritis 332
  • Molecular diagnostics and the microbiome 333
  • Human Microbiome Project 333
  • Application of metagenomics to study of the microbiome 333
  • MicroBiome Analysis Center 334
  • Concluding remarks and future prospects of diagnosis of infections 334
  • Rapid point-of-care diagnosis of infection 335
  • Diagnosis of viruses using protein fingerprinting 337
  • QIAplex PCR multiplex technology 337
  • Companies involved in molecular diagnosis of infectious diseases 338

8. Molecular Diagnosis of Cancer 342

  • Introduction 342
  • Cancer genomics 342
  • Cancer genes 343
  • Oncogenes 343
  • Tumor Suppressor Genes 343
  • p53 344
  • p16 345
  • CNVs in cancer 345
  • Allele-specific copy number analysis of tumors 346
  • Viruses and cancer 346
  • Detecting viral agents in cancer 347
  • Conventional cancer diagnosis 348
  • Molecular techniques for cancer diagnosis 348
  • Genome analysis at the molecular level 350
  • Mutation detection at molecular level 350
  • Expression profiling of tumor cells sorted by flow cytometry 351
  • MicroRNA expression profiling for cancer diagnostics 351
  • Biomarkers in cancer 351
  • Circulating nucleosomes in serum of cancer patients 352
  • Detection of DNA methylation 352
  • eTag assay system for cancer biomarkers 354
  • HAAH as a biomarker for cancer 355
  • LigAmp for detection of gene mutations in cancer 355
  • Mitochondrial DNA as a cancer biomarker 355
  • Oncoproteins as biomarkers for cancer 356
  • Sequencing-based approaches for detection of cancer biomarkers 356
  • Molecular fingerprinting of cancer 357
  • Fluorescent in situ hybridization 357
  • Genetic analysis of cancer 358
  • Comparative genomic hybridization in cancer diagnostics 358
  • Loss of heterozygosity 358
  • Digital karyotyping 358
  • Gene expression profiles predict chromosomal instability in tumors 359
  • PCR Techniques 359
  • Realtime quantitative PCR for diagnosis of cancer 360
  • Cold-PCR 360
  • Antibody-based diagnosis of cancer 360
  • Monoclonal antibodies for diagnosis of cancer 360
  • Recombinant antibodies as a novel approach to cancer diagnosis 361
  • Combined immunological and nucleic acid tests 361
  • Combination of MAbs and RT-PCR 361
  • Immunobead RT-PCR 361
  • Assays for determining susceptibility to cancer 362
  • Gene expression profiling in cancer 362
  • Microarrays for gene expression profiling in cancer 363
  • Serial analysis of gene expression (SAGE) 363
  • DNA tags for finding genes expressed in cancer 363
  • Suppression subtractive hybridization 364
  • Measurement of telomerase activity 364
  • Detection of circulating tumor cells in blood 365
  • Biochips/microfluidics for detection of CTCs 365
  • CellSearch 366
  • CellTracksR AutoPrepR System 366
  • CTCscope system for detection of CTCs 366
  • CTChip™ 366
  • Fiber-optic array scanning technology 366
  • Lab-on-chip for the isolation and detection of CTCs 367
  • MagSweeper 367
  • Future prospects of detection of cancer cells in blood 367
  • Epithelial aggregate separation and isolation 368
  • Proteomic technologies for the molecular diagnosis of cancer 368
  • Proteomic technologies for tumor biomarkers 368
  • Affibodies as contrast agents for imaging in cancer 369
  • Aptamer-based technology for protein signatures of cancer cells 369
  • Aptamer probes for in vivo diagnosis of cancer 369
  • Aptamers for combined diagnosis and therapeutics of cancer 370
  • Automated image analysis of nuclear protein distribution 370
  • Laser capture microdissection in oncology 371
  • Layered expression scanning 371
  • Membrane-type serine protease-1 371
  • Survivin and molecular diagnosis of cancer 372
  • Biochip/microarrays for cancer diagnosis 372
  • Role of DNA microarrays in gene expression profiling 373
  • Biochip detection of FHIT gene 373
  • Nanobiotechnology for early detection of cancer 373
  • Detection of nanoparticle self assembly in tumors by MRI 374
  • Differentiation between normal and cancer cells by nanosensors 374
  • Magnetic nanoparticle probes 374
  • Quantum dots for early detection of cancer 374
  • Molecular imaging of cancer 375
  • In vivo tumor illumination by adenoviral-GFP 375
  • PET for in vivo molecular diagnosis of cancer 376
  • Radiolabeled peptide-based targeting probes for cancer imaging 376
  • Xenon-enhanced MRI 376
  • Optical systems for in vivo molecular imaging of cancer 376
  • Detection of micrometastases 377
  • Molecular diagnosis of cancers of various organs 377
  • Brain tumors 378
  • Molecular diagnostic methods for brain tumors 378
  • Glioblastoma multiforme 378
  • Circulating microvesicles as biomarkers of glioblastoma 379
  • Combination of neuroimaging and DNA microarray analysis in GBM 379
  • Medulloblastoma 380
  • Multigene predictor of outcome in GBM 380
  • Oligodendroglioma 380
  • Advantages and limitations of molecular diagnosis of brain tumors 380
  • Breast cancer 381
  • Breast cancer genes 381
  • Circulating nucleic acid biomarkers of breast cancer 382
  • Molecular diagnostic tests for breast cancer 383
  • Mouse ESC-based assays to evaluate mutations in BRCA2 386
  • Genomic profiles of breast cancer 386
  • Role of molecular diagnostics in management of breast cancer 387
  • Tests for prognosis of breast cancer 391
  • Prediction of recurrence in breast cancer for personalizing therapy 393
  • Cervical cancer 394
  • Colorectal cancer 395
  • ColoVantage CRC test 395
  • Detection of familial adenomatous polyposis coli 396
  • Detection of CRC at precancerous state 396
  • Detection of circulating tumor cells in colorectal cancer 396
  • Diagnosis of hereditary nonpolyposis colorectal cancer 396
  • Diagnosis of colorectal cancer from DNA in stools 397
  • Early diagnosis of colorectal cancer from blood samples 398
  • Guanylyl cyclase C tests for colorectal cancer 398
  • Minimally invasive screening for colorectal cancer 398
  • Gastric cancer 399
  • Head and neck cancer 399
  • Nanobiochip sensor technique for analysis of oral cancer biomarkers 399
  • ProteinChip for diagnosis of head and neck cancer 400
  • Hematological malignancies 400
  • Chromosome translocations 400
  • Flow cytometry in diagnosis of leukemia 400
  • Gene chip technology 400
  • Hairy-cell leukemia 401
  • Laboratory assessment of leukemia 401
  • Molecular probes 402
  • Minimal residual disease 402
  • Screening of gene mutations in chronic myeloproliferative diseases 403
  • Lung cancer 403
  • Melanoma 405
  • Ovarian cancer 406
  • Mutation of genes 406
  • Relevance of genetic testing to management of ovarian cancer 406
  • Serum biomarkers for early detection of ovarian cancer 407
  • Biomarkers of ovarian cancer 407
  • Concluding remarks on testing for ovarian cancer 408
  • Pancreatic cancer 408
  • Prostate cancer 409
  • Early detection of prostate cancer recurrence by nanotechnology 409
  • Gene expression analysis of prostate cancer 409
  • Huntingtin Interacting Protein 1 410
  • Integrative genomic and proteomic profiling of prostate cancer 410
  • LCM for diagnosis of prostate cancer 410
  • PCA3 gene detection in urine 411
  • PCR assay for assessing silencing of protein cadherin 13 gene 411
  • Prostate biopsy for detection of prostatic intraepithelial neoplasia 412
  • Prostate Core Mitomic Test™ 412
  • Screening of multiple SNPs for risk of prostate cancer 412
  • Semen testing for prostate cancer biomarkers 413
  • Serum-protein fingerprinting in prostate cancer 413
  • Thyroid cancer 414
  • Gene expression biomarkers of thyroid cancer 414
  • Multiple endocrine neoplasia type 2B as risk factor for thyroid cancer 414
  • miRNA expression profiling in thyroid cancer 415
  • Urinary bladder cancer 415
  • Role of molecular diagnostics in the management of cancer 415
  • Risk assessment and prevention of cancer 416
  • Role of molecular diagnosis in the design of future cancer therapies 416
  • Molecular classification of cancer 416
  • Determination of cancer prognosis 417
  • Prognosis by tumor classification 417
  • Prognosis by cancer gene expression 417
  • Selection of anticancer drugs based on molecular diagnosis 418
  • Integrated genome-wide analysis of cancer for diagnosis and therapy 418
  • Personalized therapy for cancer patients 418
  • Pharmacogenetics and cancer therapy 419
  • Molecular diagnostics as an aid to selection of cancer therapy 419
  • Drug resistance in cancer 420
  • Role of organizatons in molecular diagnosis of cancer 420
  • Role of NCI in molecular diagnosis of cancer 420
  • Molecular profiling of cancer 420
  • Cancer Genome Atlas 421
  • Cancer Genetic Markers of Susceptibility Project 422
  • Support for future research in molecular diagnosis of cancer 422
  • Role of the International Cancer Genome Consortium 422
  • Future prospects of molecular diagnosis of cancer 423
  • Companies involved in molecular diagnosis of cancer 423

9. Molecular Diagnostics in Biopharmaceutical Industry & Healthcare 428

  • Introduction 428
  • Molecular diagnostics in biopharmaceutical industry 428
  • Molecular diagnostic technologies and drug discovery 429
  • Molecular diagnostics and pharmacogenetics 429
  • Molecular toxicology 430
  • Gene expression studies for toxicology 431
  • Toxicogenomics 431
  • Toxicoproteomics 431
  • Mitochondrial assays 433
  • MetaChip/Datachip 433
  • Molecular diagnostics and pharmacogenomics 434
  • Molecular diagnostics and therapeutic drug monitoring 435
  • Applications molecular diagnostics in gene therapy 435
  • Use of PCR to study biodistribution of gene therapy vectors 435
  • PCR for verification of the transcription of DNA 436
  • In situ PCR for direct quantification of gene transfer into cells 436
  • Detection of retroviruses by reverse transcriptase (RT)-PCR 436
  • Assessment of safety issues of gene transfer 436
  • Quantitative PCR for monitoring the effectiveness of gene therapy 436
  • Use of FISH for analysis of adeno-associated viral vector integration 437
  • Monitoring of gene expression by green fluorescent protein 437
  • Quality control of protein therapeutics and vaccines 437
  • Detection of microbial contamination in biopharmaceutical manufacturing 438
  • Role of PCR in detecting contamination 438
  • Systems for rapid detection of contaminants 438
  • Contamination of biopharmaceuticals with prions 439
  • DNA tagging for control and tracing of drug distribution channels 439
  • Molecular diagnostics for organ transplantation 439
  • HLA typing 439
  • Sequencing for HLA typing 441
  • Commercial products for transplant molecular diagnostics 441
  • Post-cardiac transplant patient monitoring for rejection 443
  • Application of molecular diagnostics in blood transfusion 444
  • Molecular diagnostics for testing transfusion compatibility 444
  • Transmission of infections in blood transfusion 444
  • Molecular tests for screening of blood supply for viruses 445
  • Commercial molecular diagnostic technologies for blood screening 445
  • Bridge amplification technology 446
  • COBAS AmpliScreen HCV and HIV Assays 446
  • INACTINE 447
  • NucliSens Extractor system 447
  • Pall's enhanced Bacteria Detection System 447
  • PCR combined with algorithm method 448
  • Prions detection in human blood 448
  • PRISMR automated system 448
  • Procleix HIV-1/HCV Assay 449
  • West Nile virus detection in human blood 449
  • Advantages and limitations of molecular diagnostics for blood screening 450
  • Molecular epidemiology 450
  • Molecular epidemiology of genetic diseases 451
  • Role of CNVs in study of genetic epidemiology 451
  • Accumulation of CNVs with aging 452
  • Monogenic versus polygenic disorders 452
  • Critical issues facing genetic epidemiology 453
  • Molecular epidemiology of infectious diseases 453
  • Methods and purposes 453
  • Emerging infections 453
  • Human vs. non-human infections 454
  • Genetics and susceptibility to infectious disease 454
  • Molecular epidemiology of cancer 455
  • Molecular epidemiology of p53 gene mutations 455
  • Molecular epidemiology of link between virus and cancer 456
  • Molecular epidemiology and cancer prevention 456
  • SNPs and molecular epidemiology 456
  • Molecular diagnostics for identification of food-borne pathogens 456
  • Introduction 456
  • Molecular diagnostic methods used in food-borne infections 457
  • Limitations of use of molecular probes in food analysis 458
  • Detection of Listeria-contaminated foods 458
  • Optical biosensor for detection of Listeria 458
  • Real-time PCR for detection of Listeria 459
  • Detection of Salmonella 459
  • MicroSEQR Salmonella Detection Kit 459
  • E. Coli detection 459
  • MicroSEQR E. Coli Detection Kit 459
  • DuPont Bax system 460
  • Detection of rare strains of E. Coli 460
  • Companies with technologies for food pathogen detection 461
  • Transmissible spongiform encephalopathies (TSEs) 462
  • Basis of molecular diagnosis of prion diseases 462
  • Molecular diagnosis of TSEs 463
  • Companies involved in developing molecular diagnostics for TSEs 465
  • Detection of genetically modified organisms in food 466
  • Molecular diagnostics for detection of doping in sports 467
  • Screening of synthetic glucocorticosteroids in human urine 467
  • Detection of gene doping 467
  • Role of molecular diagnostics in future healthcare 468
  • Translation of genomic research into genetic testing for healthcare 468
  • Molecular diagnostics and disease management 469
  • Role of genetic biomarkers in disease management 469
  • Role of molecular diagnostics in personalized medicine 469
  • Integrated healthcare 470
  • Screening 470
  • Early diagnosis 470
  • Prevention 470
  • Therapy based on molecular diagnosis 471
  • Monitoring of therapy 471
  • Advantages and limitations of integrated healthcare 471
  • Commercially available systems for integrated healthcare 472
  • Combination of diagnostics and therapeutics 472
  • Companion diagnostics 472
  • Companies involved in companion diagnostics 472
  • Point-of-care diagnosis 474
  • Technologies for point-of-care diagnosis 475
  • Biochips for POC diagnosis 476
  • Advantages versus disadvantages of POC diagnosis 478
  • Future prospects of POC testing 478
  • Companies developing POC diagnosis 479
  • The impact of molecular diagnostics on clinical laboratory practice 481

10. Molecular Diagnostics in Forensic Medicine and Biological Warfare 482

  • Application of molecular diagnostics in forensic medicine 482
  • Technologies 482
  • ABO genotyping 482
  • DNA analysis for identification of ancient or historical specimens 483
  • Extraction of DNA from forensic samples 483
  • Fluorescent detection systems 483
  • Mitochondrial DNA (mtDNA) analysis 483
  • Pressure cycling technology for forensic applications 484
  • Polymorphic Alu insertions 484
  • Single Nucleotide Polymorphisms (SNP) analysis 484
  • Short tandem repeat (STR) 485
  • Applications 485
  • Applications in criminology 486
  • Identification of remains of military personnel 487
  • Identification of remains of victims of mass disasters 487
  • Parentage testing 489
  • Gender determination 490
  • Companies developing molecular diagnostics for forensic science 490
  • Molecular detection of biological warfare agents 491
  • Introduction to biological warfare agents 491
  • Role of PCR in the diagnosis of biological warfare agents 492
  • Multiplex PCR microarray assay to detect bioterror pathogens in blood 493
  • Laboratory diagnosis of Anthrax 493
  • Challenges in diagnosis of biological warfare agents 494
  • US government efforts for detection of biological warfare agents 494
  • The US Army Medical Research Institute of Infectious Diseases 495
  • Homeland Security Advance Research Projects Agency 495
  • Handheld Isothermal Silver Standard Sensor 496
  • Commercial development of diagnostic devices for biological agents 496
  • Companies developing diagnostic devices for biological agents 496
  • Biodefence microarray 499
  • Identification of genetic markers of individual pathogens 499
  • Microbial Identification System based on OptiChip™ 499
  • Hand-Held Advanced Nucleic Acid Analyzer 500
  • Nanogen's portable detection device 500
  • Nanode Array Sensor Microchips 500
  • MicroChemLab 501
  • BioThreat Alert Test Strip 501
  • Benchtop living cell biosensor 501
  • BioForce NanoArray sensor technology 502
  • QTL handheld biosensor 502
  • Analyte 2000 biosensor 502
  • Airborne bacterial spore detection technology 502
  • Destruction and detection of anthrax by lysin 503
  • Biosensor based on mass spectrometry of microorganisms's RNA 503
  • Bead ARray Counter 503
  • ProteinChip-based detection of bioterroism agents 504
  • TIGER biosensor 504
  • The PathAlert™ Detection System 504
  • VereThreat™ 505
  • Concluding remarks about biodefense applications of diagnostics 505

11. References 506

Tables

  • Table 1-1: Landmarks in development of molecular technology and its application to diagnosis 26
  • Table 1-2: Applications of molecular diagnostics 47
  • Table 2-1: Companies with products for nucleic acid isolation 57
  • Table 2-2: Some commercially available real-time PCR systems 63
  • Table 2-3: Applications of real-time PCR 66
  • Table 2-4: A selection of companies with commercially available FISH diagnostics 92
  • Table 2-5: Selected companies with RNA diagnostic tests 93
  • Table 2-6: Companies involved in whole genome amplification 102
  • Table 2-7: Companies involved in sequencing 105
  • Table 2-8: Companies involved in application of sequencing in molecular diagnostics 107
  • Table 2-9: Comparison of methods of identification of unknown DNA sequences 109
  • Table 2-10: Classification of methods of gene expression analysis 110
  • Table 2-11: A selection of companies with gene expression technologies 115
  • Table 2-12: Companies involved in developing PNA diagnostics 119
  • Table 2-13: Companies with bead-based diagnostic assay platforms 122
  • Table 2-14: Companies developing nucleic acid lateral flow molecular diagnostics 125
  • Table 3-1: Applications of biochip technology in relation to molecular diagnostics 126
  • Table 3-2: Companies developing whole genome chips/microarrays 132
  • Table 3-3: Companies involved in biochips for molecular diagnostics 133
  • Table 3-4: Companies developing microfluidic technologies 138
  • Table 3-5: Biosensor technologies with potential applications in molecular diagnostics 139
  • Table 3-6: Important applications of biosensors 149
  • Table 3-7: Companies involved in application of biosensors in molecular diagnostics 149
  • Table 3-8: Selected labels for nucleic acid detection 151
  • Table 3-9: Selected companies with fluorescence and chemiluminescence products 152
  • Table 3-10: Companies involved in molecular beacon manufacture and research 154
  • Table 3-11: Selected companies involved in molecular imaging 162
  • Table 3-12: Nanotechnologies with potential applications in molecular diagnostics 163
  • Table 3-13: Companies developing nanomolecular diagnostics 172
  • Table 4-1: Applications of protein biochips/microarrays 182
  • Table 4-2: Companies involved in developing diagnostic applications of protein biochips 189
  • Table 4-3: Disease-specific proteins in the cerebrospinal fluid of patients 192
  • Table 5-1: Mutation detection technologies 200
  • Table 5-2: Technologies for SNP analysis 208
  • Table 5-3: A sampling of companies involved in technologies for SNP genotyping 217
  • Table 5-4: Application of preimplantation genetic diagnosis in monogenic disorders 231
  • Table 5-5: Companies involved in prenatal/preimplantation diagnostics 232
  • Table 5-6: CFTR genotyping in cystic fibrosis - companies and technologies 234
  • Table 5-7: X-linked immunodeficiency disorders 238
  • Table 5-8: Available molecular diagnostics for neurogenetic diseases 245
  • Table 5-9: Companies offering genetic screening tests directly to consumers 255
  • Table 6-1: Genes that cause cardiovascular diseases 256
  • Table 6-2: Molecular diagnostics for cardiovascular diseases: commercial development 263
  • Table 7-1: Molecular techniques for the diagnosis of infections 264
  • Table 7-2: Bacteria that can be detected by molecular diagnostic tests 280
  • Table 7-3: Commercially available molecular diagnostics for fungal infections 292
  • Table 7-4: Viruses that can be detected by recombinant DNA methods 295
  • Table 7-5: Companies with molecular diagnostics for avian influenza virus H5N1 318
  • Table 7-6: Companies with molecular diagnostics for influenza virus H1N1 322
  • Table 7-7: Companies developing POC tests for the diagnosis of infections 335
  • Table 7-8: Selected companies involved in molecular diagnosis of infections 338
  • Table 8-1: Estimated new cases of cancer in the US of most involved organs - 2010 342
  • Table 8-2: Tumor suppressor genes, their chromosomal location, function, and associated tumors 344
  • Table 8-3: Viruses linked to human cancer 346
  • Table 8-4: A classification of molecular diagnostic methods in cancer 349
  • Table 8-5: Desirable characteristics of biomarkers for cancer 351
  • Table 8-6: Approved monoclonal antibodies for cancer diagnosis 361
  • Table 8-7: Methods for comparison of gene-expression profilling in tumor specimens 362
  • Table 8-8: Impact of in vivo molecular imaging of cancer on oncology practice 377
  • Table 8-9: Molecular diagnostic tests for breast cancer 383
  • Table 8-10: Companies developing cancer molecular diagnostics 424
  • Table 9-1: Applications of molecular diagnostics in the biopharmaceutical industry 428
  • Table 9-2: Molecular diagnostic technologies for drug discovery 429
  • Table 9-3: Molecular diagnostic technologies used for pharmacogenetic studies 429
  • Table 9-4: Companies with novel molecular toxicology technologies 430
  • Table 9-5: Applications of molecular diagnostics in gene therapy 435
  • Table 9-6: Companies involved in transplant molecular diagnostics 441
  • Table 9-7: Companies involved in molecular diagnostics of blood transfusions 445
  • Table 9-8: Pathogenic bacteria in food and targets for molecular diagnostic probes 457
  • Table 9-9: Companies involved in molecular diagnostics for food-borne infections 461
  • Table 9-10: Testing for harmful prions in brain tissue from dead cattle 463
  • Table 9-11: Companies involved in developing molecular diagnostics for TSEs 466
  • Table 9-12: Companies involved in companion diagnostics 473
  • Table 9-13: Applications of point-of-care diagnosis 474
  • Table 9-14: Companies developing point-of-care diagnostic tests 479
  • Table 10-1: Forensic and legal applications of molecular diagnostics. 485
  • Table 10-2: Molecular technologies used for forensic applications 490
  • Table 10-3: Classification of biological and chemical agents used as weapons of mass destruction 491
  • Table 10-4: Biological warfare agents that can be identified by PCR methods 492
  • Table 10-5: Companies developing detection devices for biological warfare agents 496

Figures

  • Figure 1-1: Relation of molecular diagnostics to other technologies 48
  • Figure 2-1: Rolling circle amplification technology 75
  • Figure 2-2: A schematic view of the Invader operating system 82
  • Figure 2-3: Principle of fluorescent in situ hybridization 87
  • Figure 2-4: Repli-G system of QIAGEN 103
  • Figure 2-5: DNA sequencing process 105
  • Figure 2-6: Electrochemical detection of DNA 121
  • Figure 2-7: Elements of a Scorpions primer 124
  • Figure 3-1: Affymetrix GeneChip technology 127
  • Figure 3-2: Basic principle of a biosensor 139
  • Figure 3-3: Surface plasmon resonance (SPR) technology 144
  • Figure 7-1: Use of DNA chips in diagnosing microbial infections 268
  • Figure 7-2: High throughput DNA pyrosequencing for pathogen discovery 272

Part II

12. Ethics, Patents and Regulatory issues 6

  • Introduction 6
  • Ethical concerns about genetic diagnosis 6
  • Ethical guidelines for molecular diagnostics 7
  • Ethical aspects of direct-to-consumer genetic services 8
  • US public attitudes about genetic testing 9
  • Opinion of European geneticists about DTC genetic testing 9
  • Genetic testing for susceptibility to adult-onset cancer 9
  • Ethics of preimplantation genetic diagnosis 10
  • Preimplantation genetic diagnosis to screen for hereditary diseases 10
  • PGD to test for susceptibiliy to cancer 10
  • PGD and stem cells 11
  • Genetic research on stored tissues 11
  • Informed consent in clinical trials of in vitro devices 12
  • Concluding remarks about ethical issues 12
  • Insurance underwriting and gene tests 12
  • Should genetic information be available to health insurers? 13
  • A need for the re-examination of current views 13
  • Genetic Information Nondiscrimination Act of US 14
  • Impact of the US health care reform bill on genetic testing issues 14
  • Patents for molecular diagnostics 14
  • PCR patents 14
  • Patenting DNA sequences 14
  • US policy on gene patenting relevant to molecular diagnostics 15
  • The impact of disease gene patents on molecular diagnostics 16
  • Licensing problems associated with genetic testing 16
  • BRCA1 and BRCA2 gene patents 16
  • Role of the WHO in genetic testing standards 17
  • NIH's Genetic Testing Registry 18
  • Regulatory issues in the US 18
  • Assay Migration Studies for In Vitro Diagnostic Devices 18
  • Assessment of diagnostic accuracy 18
  • Sensitivity and specificity 19
  • Documentation of diagnostic accuracy 19
  • Discovery of incidental findings on genetic screening 20
  • Evaluation of companion diagnostics/therapeutic for cancer 21
  • FDA regulation of multivariate index assays 21
  • FDA guidance for IVDs to detect pathogens 22
  • FDA guidelines for devices to detect and differentiate HPV 23
  • FDA's Microarray Quality Control 23
  • FDA and point-of-care diagnosis 24
  • Genetic testing of rare disorders 24
  • Guidelines for developing omics-based tests 25
  • Shared responsibility on oversight of omics-based tests 25
  • Guidelines for use of sequencing for diagnosis 26
  • Quality control of molecular diagnostic laboratory procedures 27
  • Quality assurance of rna expression profiling 27
  • Quality control of point-of-care tests 28
  • Regulation of IVD by the FDA 28
  • Regulation of in vitro companion diagnostics by the FDA 29
  • Regulation of in vivo diagnostics by the FDA 30
  • Regulation of laboratory developed tests 31
  • Home-brew tests 31
  • Laboratory-developed tests used by Medicare recipients 31
  • Oversight of LDTs by the FDA 32
  • Regulatory aspects of FISH 32
  • Regulation of genetic testing 32
  • Role of the FDA in genetic testing 32
  • Regulation of direct-to-consumer genetic testing 33
  • Need for regulatory oversight of DTC 33
  • Regulatory issues concerning blood and plasma products 35
  • United States Diagnostics Standards 35
  • Regulation of in vitro diagnostics in the EU 36
  • EU regulations for testing of blood products 36
  • Regulation of genetic testing in EU 36
  • Evaluation of diagnostic laboratory tests in the UK 38
  • Pre-implantation genetic diagnosis in the UK 38

13. Markets for Molecular Diagnostics 40

  • Introduction 40
  • Methods for study of molecular diagnostic markets 40
  • The overall market for diagnostic technologies 41
  • Molecular diagnostic markets according to technologies 41
  • Marketing strategies according to technologies 42
  • Nucleic acid isolation market 42
  • Market for PCR-based tests 42
  • Markets for PCR instrumentation 42
  • Markets for real-time PCR and qRT-PCR 43
  • PCR market players 43
  • DNA sequencing market 44
  • Cytogenetic market 44
  • Market for FISH technologies 44
  • Biochip/microarray market 45
  • Biosensor market 45
  • Nanobiotechnology for molecular diagnostics 45
  • Markets for gene expression technologies 46
  • Reagents and other disposable laboratory materials 46
  • Market for immunochemistry diagnostic 46
  • Markets for tissue diagnostics 46
  • Molecular diagnostic markets according to therapeutic areas 46
  • Genetic disorders 47
  • Prenatal testing 48
  • Cancer 48
  • Potential markets for cancer diagnosis according to type of cancer 49
  • Infectious diseases 50
  • Sexually transmitted diseases 52
  • Hospital-acquired infections 52
  • Testing for HIV drug resistance 53
  • Potential markets for avian influenza diagnostics 53
  • Cardiovascular diseases 54
  • Neurological disorders 54
  • Food testing 54
  • Screening of blood for transfusion 55
  • Tissue typing for transplantation 55
  • Molecular diagnostic markets relevant to pharmaceutical industry 55
  • Molecular diagnosis and personalized medicine markets 55
  • Growth of markets relevant to personalized medicine 55
  • Marketing opportunities according to geographic areas 56
  • Unmet needs in molecular diagnostics 57
  • Major market trends 57
  • Markets according to home-brew and FDA-approved tests 57
  • Decentralization of molecular diagnostics 58
  • Point-of-care testing 58
  • Development of personalized medicine 59
  • Cost of sequencing the human genome 59
  • Cost of genotyping 60
  • Marketing companion diagnostics for personalized medicine 60
  • Development of low-cost tests 61
  • Simplification of test procedures 61
  • Increasing role of proteomics in clinical diagnostics 61
  • Forensic and legal applications 62
  • Veterinary molecular diagnostics 62
  • Marketing strategies 62
  • Role of alliances in commercialization of molecular diagnostics 63
  • Acquisitions vs collaborations 63
  • Analysis of collaborations in molecular diagnostics 66
  • Licensing of the technologies 67
  • Strategies related to laboratory facilities and technologies 67
  • Strategies relevant to the healthcare system 68
  • Cost-Benefit studies 68
  • Genetic susceptibility testing 68
  • Preventive medicine strategies 69
  • Targeting treatable and common diseases 69
  • Information/education 69
  • Physician education 69
  • Patient education 70
  • European diagnostic information platform 70
  • Regulatory strategies 71
  • Merger of in vitro and in vivo diagnostics 71
  • Integration of diagnostics with therapeutics 71
  • Diagnostic applications in clinical trials 71
  • Prospects for development of new technologies 72
  • Drivers for the development of molecular diagnostics 72
  • Factors slowing the development of molecular diagnostics 72
  • Government support of research relevant to molecular diagnostics 73
  • Cost of sequencing the human genome 73
  • European projects for improving molecular diagnostics 75
  • European Consortium for developing new DNA analysis tools 75
  • EU project for improvement of IVD tools procedures 76
  • Genetic knowledge parks in the UK 76
  • Molecular diagnostic opportunities in defense against bioterrorism 76
  • Molecular diagnostics for food safety 77
  • POC diagnostics for the developing countries 77

14. Companies involved in molecular diagnostics 78

  • Introduction 78
  • Major players in molecular diagnostics 78
  • Profiles of selected companies 79
  • Collaborations 467

Tables

  • Table 13-1: Share of in vitro diagnostics in the global diagnostic market 2011-2021 41
  • Table 13-2: Molecular diagnostics markets according to technologies from 2011-2021 41
  • Table 13-3: PCR market 2011-2021 42
  • Table 13-4: Molecular diagnostics markets according to applications 2011-2021 47
  • Table 13-5: Markets in 2011 for tests to screen healthy persons for genetic disorders 48
  • Table 13-6: Markets in 2011 for molecular diagnostic screening tests for cancer 49
  • Table 13-7: Molecular diagnostic markets for selected cancers 2011-2021 49
  • Table 13-8: Markets value in 2011 for molecular diagnostic screening for infections 51
  • Table 13-9: Future markets for molecular diagnosis of infections 2012-2016 51
  • Table 13-10: Future markets for HAI diagnostics 2012-2016 52
  • Table 13-11: Growth of markets relevant to personalized medicine 2011-2021 56
  • Table 13-12: Molecular diagnostic markets according to geographical areas 2011-2021 56
  • Table 13-13: Molecular diagnostic markets according to home-brew and approved tests 58
  • Table 13-14: Marketing strategies for molecular diagnostics 62
  • Table 13-15: Acquisitions of molecular diagnostic companies 63
  • Table 13-16: Advantages of the integration of diagnostics with therapeutics 71
  • Table 14-1: Top ten players in molecular diagnostics 78
  • Table 14-2: Collaborations of companies in molecular diagnostics 467

Figures

  • Figure 13-1: Unmet needs in applications of molecular diagnostics 57
  • Figure 13-2: Proportion of various areas in molecular diagnostic collaborations 67
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