Cell-Based Assays for Drug Discovery

The area of drug discovery tools is one of the newest and most important sectors of pharmaceutical research and development. The term drug discovery tools usually refers to high-content screening (HCS) and analysis and is composed of those applications that require sufficient levels of sample throughput, whereby complex cellular events and phenotypes can be studied. Elements of drug performance like toxicity and specificity can be established simultaneously using mixed cell types-primary cells, cell lines, cell subpopulations. HCS seeks to assess the impact of phenotypic and cellular changes that are brought about by gene modification (such as with RNA interference (RNAi) approaches) and/or drug (or compound) treatment. The purpose of this examination by TriMark Publications is to describe the specific segments of the global drug discovery tools market. Within this area, the report covers those segments that are highly active in terms of innovation and growth. Specifically, this study examines the markets for small lab equipment all the way up to highly automated, large automated platforms, as well as accessory equipment such as reagents, supplies and manufacturers' original equipment manufacturer (OEM) additional equipment.
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1. Overview 4
1.1 Objectives of the Report 4
1.2 Methodology 5
1.3 Scope of the Report 6
1.4 Executive Summary 7

2. Technologies and Product Offering for High-Content Analysis 10
2.1 Definition of High-Content Analysis and Why it is so Attractive a Discipline 11
2.2 Classes of Measurements Possible with High-Content Analysis Approaches and Biologies Interrogated 14
2.3 Instrumentation Platforms for High-Content Analysis 17
2.3.1 High-Content Screening Technology 17
2.4 Reagent and Assay Platforms for High-Content Analysis 24
2.5 Cell-based Screening Technologies in Drug Development 28
2.5.1 Applications of Cell-based Assays 28
2.5.2 Pharma Drug Discovery Paradigm and Compound Screening 28
2.5.3 High-Content Analysis in the Biopharmaceutical Industry 29

3. Market Analysis of the High-Content Tools Space 31
3.1 High-Content Analysis Market Size and Growth 31
3.2 Market Survey to Assess Qualitative and Quantitative Parameters of the High-Content Analysis Space 31
3.3 Experimental and Research Trends in High-Content Analysis 33
3.4 Challenges and Market Drivers in High-Content Analysis 38
3.4.1 Barriers to High-Content Analysis 40
3.4.2 Drivers of High-Content Analysis 41
3.5 High-Content Analysis in Combination with RNAi 41
3.6 Market Landscape of Instrumentation for High-Content Analysis 43
3.7 Reagents and Assays Usage in High-Content Analysis 47
3.8 Trends in High-Content Analysis Assays/Reagents Space-Major Product Vendors 50
3.9 Emerging Market Trends in High-Content Analysis 52
3.10 Market Forecasts for the High-Content Analysis Space 54
3.11 Use of HCS in Pharmaceutical Companies 56
3.12 Qualitative Opportunities and Challenges for Market Adoption 57

4. Strategic Analysis of the High-Content Tools Space 58
4.1 High-Content Analysis Market Structure 58
4.2 Description of the Drug Discovery Marketplace and Definition of the Field 58
4.3 Key Market Drivers and Challenges in the High-Content Analysis Space 59
4.4 Consolidated Picture of the High-Content Analysis Marketplace 62
4.5 High-Content Analysis Market Sectors and Growth Rate 64
4.6 Vendors of High-Content Analysis Technology 64

5. High-Content Analysis Technology Platforms 65
5.1 Methods of Digital Imaging 65
5.2 Fluorescence Microscopy 65
5.3 Major High-Content Analysis Instrumentation 66
5.3.1 High-Content Analysis Platforms to Support GPCR Screening 67
5.4 High-Content Analysis Reagents 67
5.5 Imaging Software 68
5.6 Enterprise-Level IT Solution to Support High-Content Screening Experiments 68
5.6.1 Image Analysis Algorithms 69
5.7 Use of RNAi in High-Content Analysis 70
5.8 Industry Alliance to Leverage RNAi and High-Content Analysis 70
5.9 Emerging Trends in High-Content Analysis Technology Platforms 71

6. High-Content Analysis in Drug Selection, Screening and Biomarker Discovery 72
6.1 Stem Cells Used as a Drug Discovery Tool 73
6.2 Cellular Systems Biology for Development of Toxicity Panels in Drug Safety Testing 73
6.3 Drug Discovery Companies Marketing Cell-based Assays 74
6.4 Companies Using Cell-based Assays in Drug Discovery Programs 77
6.4.1 Phenotypic Drug Discovery (PDD) 77
6.4.2 Application of Quantitative High-Throughput Screening to High-Content Analysis of Cell-based Assays 78
6.4.3 Application of High-Content Fingerprinting to Oncology Drug Discovery: Focus on In vitro and In vivo Phenocopying and Cancer Stem Cell Analysis 78
6.5 Target Discovery and Validation by RNAi Screening 78
6.6 FLIM-FRET Methodology 78
6.7 Multidimensional Fluorescence Imaging (MDFI) Technology 79

7. Company Profiles and Glossary of Terms in High-Content Analysis 80
7.1 Acumen Pharmaceuticals, Inc. 80
7.2 Applied Biosystems 80
7.3 Becton, Dickinson and Company 84
7.4 Beckman Coulter, Inc. 86
7.5 Blueshift Biotechnologies, Inc. 91
7.6 Caden Biosciences, Inc. 91
7.7 Cellomics, Inc. 91
7.8 Cellumen, Inc. 92
7.9 Cenix BioScience 92
7.10 Cyntellect 93
7.11 Definiens 93
7.12 DiscoveRx 93
7.13 Euroscreen 94
7.14 Evotec Technologies 94
7.15 Fisher BioImage 94
7.16 General Electric, GE Healthcare Advanced Systems 95
7.17 Guava Technologies, Inc. 96
7.18 Millipore 96
7.19 Molecular Devices Corporation 97
7.20 NIH Chemical Genomics Center 100
7.21 PerkinElmer 100
7.22 Spotfire 104
7.23 Translational Genomics Research Institute 104
7.24 Vala Sciences, Inc. 105

8. Glossary of Terms in the High-Content Analysis Space 106
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Table 2.1: Comparison of the Key Features of High-Content Analysis and High-Content Screening 12
Table 2.2: Impact of High-Content Analysis on Drug Discovery-Several Drivers are Addressed 12
Table 2.3: Biological Application Areas Associated with High-Content Analysis 13
Table 2.4: Classes of Measurements and Targets Identified Using Phenotypic Screening (High-Content Analysis) 14
Table 2.5: Classes of Cellular Measurements Possible with Fluorescent Protein Biosensors 15
Table 2.6: Multi-Parameter High-Content Analysis Assays to Study Biological Systems in Life Science Research and Drug Discovery-Demonstrates the Breadth and Scalability of the High-Content Analysis Approach 17
Table 2.7: Companies Offering Systems for High-Throughput Imaging 19
Table 2.8: Comparison of the Major Instrumentation Platforms and their Associated Specifications for High-Content Analysis-I 20
Table 2.9: Comparison of the Major Instrumentation Platforms and their Associated Specifications for High-Content Analysis-II 20
Table 2.10: Price Points and Target Markets of the Various High-Content Analysis Instrument Platforms 21
Table 2.11: Companies Offering Flow Cytometry Products and Services 21
Table 2.12: Integrated Product Platforms Offered by the Different High-Content Analysis Vendors 23
Table 2.13: Biologies interrogated by Cellomics High-Content Analysis Assays 24
Table 2.14: Cellomics HitKit® High-Content Analysis Assay/Reagent Kits and the Therapeutic Areas where they Find Application 25
Table 2.15: Assay/Reagent Portfolio of Millipore Addressing High-Content Analysis Applications 26
Table 2.16: Cell Lines for GPCR High-Content Analysis that can be Deployed onto the BD Biosciences/Atto Pathway HT™ Instrument Platform 26
Table 2.17: Examples of High-Content Screens 29
Table 3.1: What Fraction of High-Content Analysis Assays are Cell-based Versus Biochemical-based 33
Table 4.1: Comparison of the Key Features of High-Content Analysis and High-Content Screening 59
Table 4.2: Snapshot of the Various High-Content Analysis Assays Demonstrating the Scalability of this Discipline 61
Table 5.1: Modes of Digital Imaging 65
Table 5.2: Modes of Fluorescence 65
Table 5.3: Major High-Content Analysis Instrumentation 66
Table 5.4: Image Analysis Algorithms 69

Figure 2.1: Scope of Biological Parameters Addressed via a Typical High-Content Analysis Experiment 13
Figure 2.2: Classes of Assays in Life Science Research and Drug Discovery Illustrating the Relationship between Cell-based Assays and High-Content Analysis 14
Figure 2.3: New Paradigm of Drug Discovery and Development Illustrating the Central and Essential Role of Screening 16
Figure 2.4: Cumulative and New Drug Targets 30
Figure 3.1: Breakout of Market Survey Respondents by Geographical Location 31
Figure 3.2: Breakout of Market Survey Respondents by Affiliation-Academic, Commercial, Vendor 31
Figure 3.3: Segmentation of Respondent Pool Based upon Usage of High-Content Analysis in its Research Activities 32
Figure 3.4: Segmentation of the Survey Respondent Pool Based upon the Length of Time they have been Using High-Content Analysis in their Research Activities 32
Figure 3.5: Number of Parameters Studied Simultaneously in High-Content Analysis Assays-Multivariate (Multi-Parameter) Analyses 34
Figure 3.6: Key Biological Processes Studied Utilizing High-Content Analysis Tools 35
Figure 3.7: Breakout of High-Content Analysis Assays Currently Performed or Expected to be Performed in the Future by Biological Pathway (or Target) 36
Figure 3.8: Breakout of High-Content Analysis Experiments Performed Per Week (Distributed in our Respondent Pool) Across the Various Biological Pathways (and Targets) 36
Figure 3.9: Which of the Biologies (Pathways/Targets) Addressed Using High-Content Analysis-based Approaches are Growing in Importance or Declining? 37
Figure 3.10: In Which Environment are High-Content Analysis Assays Performed-Primary Screen, Secondary Screen, ADME/Tox Screen? 38
Figure 3.11: Key Challenges Faced by the Research Community in their Practice of High-Content Analysis 39
Figure 3.12: Various Drivers that are Leading the Research Community to Perform High-Content Analysis 40
Figure 3.13: High-Content Analysis Together with RNAi-Current and Future Experimental Formats 42
Figure 3.14: High-Content Analysis Together with RNAi-Number of Experiments Performed Per Month by the Survey Respondent Pool 42
Figure 3.15: Growing and Steady Usage of the Various Formats where RNAi is coupled with High-Content Analysis 43
Figure 3.16: Penetration of the Different High-Content Analysis Instrumentation Platforms into the Marketplace 44
Figure 3.17: Instrumentation Platforms for High-Content Analysis Ranked by Top Choice and Second Tier 45
Figure 3.18: High-Content Analysis Instrumentation and where they Lie on the Throughput Curve 46
Figure 3.19: Top Instrumentation Value Drivers in the High-Content Analysis Space 46
Figure 3.20: Important Sub-Cellular Features Studied via High-Content Analysis Approaches 47
Figure 3.21: Breakout of End-Point Versus Kinetic Assays in the High-Content Analysis Space 48
Figure 3.22: Types of Cellular Targets Studied Using High-Content Analysis Approaches 48
Figure 3.23: Top-most Target Class Being Studied Utilizing High-Content Analysis Approaches 49
Figure 3.24: Distribution of High-Content Analysis Experiments across the Respondent Pool-Number of Experiments Performed Per Week 49
Figure 3.25: Average Reagent/Assay Costs Per High-Content Analysis Experiment 50
Figure 3.26: Stratification of Reagent/Assay Suppliers into the High-Content Analysis Space 51
Figure 3.27: Monthly Reagent/Assay Purchases for High-Content Analysis by the End-user Community from the Various Vendors Offering Products into the Space 51
Figure 3.28: Growth or Decline in Importance of the Various High-Content Analysis Vendors to the End-user Community 52
Figure 3.29: Percentage of High-Content Analysis Experiments that Involve GFP across the Market Landscape 53
Figure 3.30: Breakout of High-Content Analysis Reagents Marketplace: Home-Brew Versus Off-the-Shelf 53
Figure 3.31: Breakout of Spending into the Various Components of the High-Content Analysis Discipline 54
Figure 3.32: Forecast Growth of the Total Screening Space-Broken-out by Primary Screening, Secondary Screening (includes High-Content Analysis as a Subset) and ADME/Tox, 2004-2010 55
Figure 3.33: Forecast Growth of the Screening Space-Broken-out by Cell-based Assays and Biochemical Assays, 2004-2010 56
Figure 4.1: Drug Discovery and Development Ensemble and the Position of the Various Segments of High-Content Analysis in the Space 61
Figure 4.2: Relative Size and Position of the High-Content Analysis Space in the Overall Scheme of the Life Science Tools Marketplace 63
Figure 5.1: High-Content Analysis-Positional Biosensors Using Caspases and Monitoring the Translocation of a Tagged Protein from the Cytoplasm to the Nucleus 69
Figure 6.1: Druggability of the Various Target Classes: Breakout of the Drug Targets Today into their Constituent Classes 72
Figure 6.2: GPCR Assay Technologies 73
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