Label‐Free Imaging and Temporal Signature in Phenotypic Cellular Assays: A New Approach to High‐Content Screening

Julio Martin1

1 GlaxoSmithKline, Tres Cantos, Spain
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 9.13
DOI:  10.1002/0471141755.ph0913s50
Online Posting Date:  September, 2010
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Abstract

Some drug targets are not amenable to screening because of the lack of a practical or validated biological assay. Likewise, some screening assays may not be predictive of compound activity in a more disease‐relevant scenario, or assay development may demand excessive allocation of resources (i.e., time, money or personnel) with limited knowledge of the actual tractability of the target. Label‐free methodologies, implemented in microtiter plate format, may help address these issues and complement, simplify, or facilitate assays. Label‐free biosensors, based on grating resonance or electrical impedance, are versatile platforms for detecting phenotypic changes in both engineered and native cells. Their non‐invasive nature allows for the kinetic monitoring of multiple real‐time cellular responses to external stimuli, as well as for the use of successive pharmacological challenges. The temporal signature recorded for a particular stimulus is characteristic of the cell type and the signaling pathway activated upon binding of a ligand to its receptor. Cellular label‐free technology is an important technical advance in the study of functional pharmacological selectivity. Described in this overview are some of the hurdles encountered in modern drug discovery and the ways in which label‐free technologies can be used to overcome these obstacles. Curr. Protoc. Pharmacol. 50:9.13.1‐9.13.13. © 2010 by John Wiley & Sons, Inc.

Keywords: label‐free; biosensors; cell‐based assays

     
 
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Table of Contents

  • Introduction
  • What is Limiting the Development of Genomics?
  • Why aren't All Biological Assays Equally Predictive for Therapeutic Relevance?
  • Value Proposition and Advantages of Label‐Free Methodologies
  • Detection Principle of Label‐Free Methodologies for Cell‐Based Functional Assays in High‐Throughput Mode
  • Pharmacological Applications of Label‐Free Technology in Drug Discovery
  • Current and Future Challenges
  • Conclusion
  • Acknowledgements
  • Literature Cited
  • Figures
     
 
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Materials

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Literature Cited

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