The Future Of Array Technologies
Impact on drug discovery and market growth in DNA, protein and tissue arrays
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| Overview: | |
| The study of genes used to be a slow and arduous process with a single gene studied in a single experiment. The filter and blotting methods used provided limited information about other genes or how single genes interact with the collective gene product in a living organism. The advent of DNA microarrays (also referred to as biochips, DNA chips, DNA arrays, gene arrays and GeneChipsŇ), which allow analysis of many genes in a single experiment quickly and efficiently, has transformed research. Whole genomes are now available for study on a single microarray. Recently, the same technologies have been modified and applied to the study of RNA, proteins, cells and tissue samples with promising results. The new technologies have broad applications ranging from genetic screening, diagnostics and safety assessment, to proteomics and drug development. |
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By Dr CL Barton / Publication Date: 1st June 2005
Contents:
Table of Contents
The Future of Array Technologies
Executive Summary 10
Current array technologies 10
Novel and emerging array technologies 11
Array applications in drug discovery & development 12
The array market 13
Key players – competitor landscape 14
Chapter 1
Current array technologies 16
Summary 16
Introduction 17
DNA arrays 17
Microarray preparation 19
Limitations and advantages of DNA microarrays 21
RNA arrays 22
Limitations and advantages of RNA arrays 23
Protein arrays 24
Expression arrays 25
Functional arrays 27
Reverse arrays 27
Limitations and advantages of protein arrays 28
Tissue arrays 29
Cell arrays 32
Conclusions 35
Chapter 2
Novel and emerging array
technologies 38
Summary 38
Introduction 39
Advances in sample preparation 39
Laser capture microdissection (LCM) 39
Microfluidics – lab-on-a-chip technologies 40
Advantages and limitations of microfluidics and lab-on-a-chip technology 42
Applications of lab-on-a-chip devices 43
Healthcare 43
Laboratory products 45
Companies investing in microfluidics 47
ChIP-on-chip 48
Applications and commercially available products 49
Chromosome-on-a-chip 49
Chromosome-on-a-chip preparation 49
Advantages and applications of chromosome-on-a-chip technology 51
Commercially available products 51
Nanoarrays 52
Advantages of nanoarray over microarray technology 52
Applications and commercially available products 53
The BioForce Nanosciences NanoArrayer system 53
NanoInk’s NSCRIPTOR 54
Leading emerging array technology 54
Intellectual property (IP) – the patent minefield 54
Affymetrix IP portfolio 57
Incyte Genomics IP portfolio 58
Aclara IP portfolio 58
Caliper Technologies IP portfolio 59
Nanogen IP portfolio 60
Oxford Gene Technology (OGT) IP portfolio 60
Recent patents 61
Nanofluidics technology 61
ChIP-on-Chip technology 61
Conclusions 62
Chapter 3
Array applications in drug
discovery & development 64
Summary 64
Introduction 65
Array applications in drug discovery and development 66
Expression profiling 67
Gene expression studies in drug discovery 69
Protein expression studies in drug discovery 70
Expression study applications in oncology 71
Expression study applications in inflammatory disease 73
Expression study applications in CNS 73
Expression study applications in metabolic disorders 74
Expression study applications in infectious diseases 74
Expression study applications in vaccines 75
Application of array technology in target validation 75
Future applications of arrays in drug discovery 77
HTS 78
High throughput genomics 78
High throughput proteomics 79
Capture arrays 79
Interaction arrays 82
Future applications of arrays in HTS 83
Toxicology screening 84
Toxicogenomics 84
Future applications of array technology in toxicogenomics 85
Toxicoproteomics 86
Pharmacogenomics/proteomics 87
Pharmacogenomics 88
The first diagnostic array 91
The AmpliChip CYP450 test 92
Pharmacoproteomics 94
Pharmacoproteomic arrays 95
Pharma alliances with pharmacoproteomics specialists 97
Future applications of pharmacogenomics/proteomics 97
Theranostics 97
Conclusions 101
Diagnostics 102
New diagnostic arrays 106
Conclusions 107
Chapter 4
The array market 110
Summary 110
Introduction 111
The array market 112
Methodology for market sizing and forecasts 113
Market size and future trends 114
DNA array market 115
Protein array market 116
Cell & tissue array market 117
Emerging array technologies 117
Market size and future trends based on application 118
Expression profiling 120
Toxicology screening 121
Pharmacogenomics 122
HTS screening 123
Diagnostics 124
Conclusions 125
Chapter 5
Key players - competitor
landscape 128
Summary 128
Introduction 129
Major players 129
Alliances and acquisitions in the DNA array market 132
Alliances and acquisitions in the protein array market 135
Alliances and acquisitions in the tissue array market 137
Alliances and acquisitions in the emerging array technology market 138
Chapter 6
Glossary & references 142
Glossary 142
References 147
Index 152
Website references 155
List of Figures
Figure 1.1: Schematic representation of a typical DNA array preparation 18
Figure 1.2: The application of transfected cell array in gene expression 22
Figure 1.3: Schematic representation of a ‘sandwich’-type expression array 26
Figure 1.4: Schematic representation of tissue microarray production 29
Figure 1.5: Schematic representation of cell array 33
Figure 2.6: Laser capture microdissection process 40
Figure 2.7: Lab-on-a-chip technology 41
Figure 2.8: Point of care (POC) lab-on-a-chips 44
Figure 2.9: OpenArray™ Thru-Hole™ technology 46
Figure 2.10: HPLC-Chip 47
Figure 2.11: Schematic of 10nm chromatin fiber 48
Figure 2.12: Schematic overview of array CGH 50
Figure 3.13: Array technology applications in drug discovery & development 67
Figure 3.14: A typical gene expression assay 70
Figure 3.15: A typical differential protein expression assay 71
Figure 3.16: Microarrays in vaccine development 75
Figure 3.17: Optimization of lead compounds using expression profiling 76
Figure 3.18: Comparison of gene expression profiles to optimize leads 77
Figure 3.19: PMI technology 80
Figure 3.20: ProteinChip Biology system 82
Figure 3.21: GeneChip HTS system (96 array plate) 83
Figure 3.22: Strategies for analysis of toxicogenomics/proteomic data 87
Figure 3.23: SNP analysis to predict drug response 88
Figure 3.24: The first diagnostic array - AmpliChip 92
Figure 3.25: The value of theranostics to pharmaceutical product development & marketing 100
Figure 3.26: Three stages of diagnostic development 103
Figure 3.27: Potential commercial diagnostic markers 105
Figure 4.28: Array market geographical sales split, 2003 115
Figure 4.29: Proportion of sales from array market segments, 2004 118
Figure 4.30: Growth in the array market, 2004-2015 120
List of Tables:
List of Tables
Table 1.1: Steps in the design and implementation of a DNA microarray experiment 19
Table 1.2: DNA microarray applications 19
Table 1.3: A selection of DNA microarray manufacturers 20
Table 1.4: Array capacity and feature size 21
Table 1.5: RNA microarray applications 23
Table 1.6: Commercial RNAi libraries 24
Table 1.7: Protein microarray applications 25
Table 1.8: A selection of protein array manufacturers 28
Table 1.9: Tissue microarray applications 30
Table 1.10: Commercial TMA suppliers 31
Table 1.11: Tissue imaging systems adapted for TMA 31
Table 1.12: Cell microarray applications 32
Table 1.13: Commercial cell array suppliers 34
Table 2.14: Advantages and limitations of microfluidics and lab-on-a-chip technology 42
Table 2.15: Companies with an interest in microfluidics and lab-on-a-chip devices 47
Table 2.16: Selected companies applying nanotechnology in designing arrays 52
Table 2.17: Microarray technology patents registered worldwide up to April 2005 55
Table 2.18: Recent patent disputes regarding array technology 56
Table 3.19: Technology platforms for pharmacogenomic assays 89
Table 3.20: Altered drug effects in humans due to genetic polymorphism and polymorphisms of
drug transporters (DT) and receptors (R) 90
Table 3.21: Drugs extensively metabolized by CYP2C19 and CYP2D6 93
Table 3.22: Proteomic biomarkers 95
Table 4.23: Global sales of array technologies, 2004-2015 114
Table 4.24: Application of array technologies in market segments 119
Table 4.25: Sales forecasts for total array market, 2004-2015 119
Table 4.26: Array sales forecasts for expression profiling, 2004-2015 121
Table 4.27: Array sales forecasts for toxicology screening, 2004-2015 122
Table 4.28: Array sales forecasts for pharmacogenomics, 2004-2015 123
Table 4.29: Array sales forecasts for HTS, 2004-2015 124
Table 4.30: Array sales forecasts for diagnostics, 2004-2015 125
Table 5.31: Companies involved in array technologies, A-L 130
Table 5.32: Companies involved in array technologies, M-Z 131
Table 5.33: Affymetrix strategic alliances during the last 2 years 133
Table 5.34: Recent Invitrogen genomic and proteomic mergers and acquisitions 134
Table 5.35: Recent Ciphergen strategic alliances 136