Cell-Based Assays for Drug Discovery

Table of Contents

1. Overview

• 1.1 Objectives of the Report
• 1.2 Methodology
• 1.3 Scope of the Report
• 1.4 Executive Summary

2. Technologies and Product Offering for High-Content Analysis

• 2.1 Definition of High-Content Analysis and Why it is so Attractive a Discipline
• 2.2 Classes of Measurements Possible with High-Content Analysis Approaches and Biological Functions Investigated
• 2.3 Instrumentation Platforms for High-Content Analysis
  • 2.3.1 High-Content Screening Technology
• 2.4 Reagent and Assay Platforms for High-Content Analysis
• 2.5 Cell-based Screening Technologies in Drug Development
  • 2.5.1 Applications of Cell-based Assays
  • 2.5.2 Pharma Drug Discovery Paradigm and Compound Screening
  • 2.5.3 High-Content Analysis in the Biopharmaceutical Industry

3. Market Analysis of the High-Content Tools Space

• 3.1 High-Content Analysis Market Size and Growth
• 3.2 Market Survey to Assess Qualitative and Quantitative Parameters of the High-Content Analysis Space
• 3.3 Experimental and Research Trends in High-Content Analysis
• 3.4 Challenges and Market Drivers in High-Content Analysis
  • 3.4.1 Barriers to High-Content Analysis
  • 3.4.2 Drivers of High-Content Analysis
• 3.5 High-Content Analysis in Combination with RNAi
• 3.6 Market Landscape of Instrumentation for High-Content Analysis
• 3.7 Reagent and Assay Usage in High-Content Analysis
• 3.8 Trends in the High-Content Analysis Assays/Reagents Space-Major Product Vendors
• 3.9 Emerging Market Trends in High-Content Analysis
• 3.10 Market Forecasts for the High-Content Analysis Space
• 3.11 Use of HCS in Pharmaceutical Companies
• 3.12 Qualitative Opportunities and Challenges for Market Adoption

4. Strategic Analysis of the High-Content Tools Space

• 4.1 Analysis of the High-Content Market Structure
• 4.2 Description of the Drug Discovery Marketplace and Definition of the Field
• 4.3 Key Market Drivers and Challenges in the High-Content Analysis Space
• 4.4 Consolidated Picture of the High-Content Analysis Marketplace
• 4.5 High-Content Analysis Market Sectors and Growth Rate
• 4.6 Vendors of High-Content Analysis Technology

5. High-Content Analysis Technology Platforms

• 5.1 Methods of Digital Imaging
• 5.2 Fluorescence Microscopy
• 5.3 Major High-Content Analysis Instrumentation
  • 5.3.1 High-Content Analysis Platforms to Support GPCR Screening
• 5.4 High-Content Analysis Reagents
• 5.5 Imaging Software
• 5.6 Enterprise-Level IT Solutions to Support High-Content Screening Experiments
  • 5.6.1 Image Analysis Algorithms
• 5.7 Use of RNAi in High-Content Analysis
• 5.8 Industry Alliances to Leverage RNAi and High-Content Analysis
• 5.9 Emerging Trends in High-Content Analysis Technology Platforms

6. High-Content Analysis in Drug Selection, Screening and Biomarker Discovery

• 6.1 Stem Cells as Tools for Drug Discovery
• 6.2 Cellular Systems Biology for Development of Toxicity Panels in Drug Safety Testing
• 6.3 Drug Discovery Companies Marketing Cell-based Assays
• 6.4 Companies Using Cell-based Assays in Drug Discovery Programs
  • 6.4.1 Phenotypic Drug Discovery (PDD)
  • 6.4.2 Application of Quantitative High-Throughput Screening to HCA Cell-based Assays
  • 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
• 6.5 Target Discovery and Validation by RNAi Screening
• 6.6 FLIM-FRET Methodology
• 6.7 Multidimensional Fluorescence Imaging (MDFI) Technology

7. Company Profiles

• 7.1 Acumen Pharmaceuticals, Inc.
• 7.2 Acumen Bioscience (division of TTP Group)
• 7.3 Applied Biosystems
• 7.4 BD Biosciences
• 7.5 DiscoveRX
• 7.6 Evotec Technologies (acquired by PerkinElmer)
• 7.7 Fisher BioImage
• 7.8 General Electric, GE Healthcare
• 7.9 Guava Technologies (now a division of Millipore)
• 7.10 Integral Molecular (Akceli Inc.)
• 7.11 LemnaTech GmbH
• 7.12 Millipore
• 7.13 Molecular Devices Corporation, now a division of MDS Analytical Techniques
• 7.14 NIH Chemical Genomics Center
• 7.15 PerkinElmer
• 7.16 Sangamo Biosciences, Inc.
• 7.17 Spotfire (acquired by TIBCO)
• 7.18 Thermo Scientific Cellomics
• 7.19 Translational Genomics Research Institute
• 7.20 Vala Sciences, Inc.

8. Glossary of Terms in the High-Content Analysis Space

LIST OF FIGURES

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

LIST OF TABLES

• Table 2.1: Comparison of the Key Features of High-Content Analysis and High-Throughput Screening
• Table 2.2: Impact of High-Content Analysis on Drug Discovery-Impact of Several Drivers
• Table 2.3: Biological Application Areas Associated with High-Content Analysis
• Table 2.4: Classes of Measurements and Targets Identified Using Phenotypic Screening (High-Content Analysis)
• Table 2.5: Classes of Cellular Measurements Possible with Fluorescent Protein Biosensors
• Table 2.6: Multi-Parameter High-Content Analysis Assays to Study Biological Systems in Life Science Research and Drug Discovery, Demonstrating the Breadth and Scalability of the High-Content Analysis Approach
• Table 2.7: Companies Offering Systems for High-Throughput Imaging
• Table 2.8: Comparison of the Major Instrumentation Platforms and Their Associated Specifications for High-Content Analysis-I
• Table 2.9: Comparison of the Major Instrumentation Platforms and Their Associated Specifications for High-Content Analysis-II
• Table 2.10: Price Points and Target Markets of the Various High-Content Analysis Instrument Platforms
• Table 2.11: Companies Offering Flow Cytometry Products and Services
• Table 2.12: Integrated Product Platforms Offered by the Different High-Content Analysis Vendors
• Table 2.13: High-Content Analysis Assays Developed by Thermo Scientific Cellomics
• Table 2.14: Thermo Scientific Cellomics HCS Reagent Kits (formerly called "HitKits") and Their Therapeutic Areas of Application
• Table 2.15: Millipore' s HCA Assay/Reagent Portfolio
• Table 2.16: Cell Lines for GPCR High-Content Analysis that can be Deployed onto the BD Biosciences/Atto Pathway HT"! Instrument Platform
• Table 2.17: Examples of High-Content Screens
• Table 3.1: What Fraction of High-Content Analysis Assays are Cell-based Versus Biochemical-based
• Table 4.1: Comparison of the Key Features of High-Content Analysis and High-Content Screening
• Table 4.2: Snapshot of the Various HCA Assays, Demonstrating the Scalability of this Discipline
• Table 5.1: Modes of Digital Imaging
• Table 5.2: Modes of Fluorescence Microscopy
• Table 5.3: Major High-Content Analysis Instrumentation
• Table 5.4: Image Analysis Algorithms