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Live-Cell High Content Screening in Drug Development.

Milan Esner1,2, Felix Meyenhofer1,3, Marc Bickle4

  • 1High Throughput Technology Development Studio (HT-TDS), Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307, Dresden, Germany.

Methods in Molecular Biology (Clifton, N.J.)
|October 31, 2017
PubMed
Summary
This summary is machine-generated.

Automated microscopy, including high-content screening (HCS), is revolutionizing drug discovery. Live-cell imaging, though challenging, offers kinetic insights into drug action, enhancing cellular screening relevance.

Keywords:
Drug developmentEnvironmental controlImage analysisImagingKineticLive cell

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Area of Science:

  • Cellular imaging
  • Drug discovery and development
  • Automated microscopy

Background:

  • Automated microscopy and image analysis have driven the adoption of imaging modalities in drug discovery.
  • High-content screening (HCS) and high-content analysis (HCA) leverage cellular imaging for enhanced physiological relevance over biochemical screening.
  • Current drug development imaging primarily uses fixed cells, but live-cell imaging offers dynamic insights.

Purpose of the Study:

  • To summarize the challenges and advantages of implementing live-cell imaging in drug discovery.
  • To present examples of live-cell imaging applications in the drug development pipeline.
  • To discuss the motivation for performing kinetic live-cell assays.

Main Methods:

  • Review of technological advancements in automated microscopy and image analysis for HCS/HCA.
  • Discussion of live-cell imaging capabilities, including environmental chambers and onboard pipetting on HCS platforms.
  • Analysis of applications and kinetic studies in live-cell assays.

Main Results:

  • Live-cell imaging provides technically challenging yet valuable kinetic data on compound mode of action and cellular component dynamics.
  • HCS platforms increasingly incorporate features to support live-cell assays, reflecting customer demand.
  • Kinetic analysis of live-cell assays enhances the understanding of drug effects over time.

Conclusions:

  • Live-cell imaging is a crucial, albeit challenging, tool for modern drug discovery, offering kinetic and dynamic cellular information.
  • The integration of live-cell capabilities into automated microscopy systems is vital for advancing drug development.
  • Kinetic live-cell assays provide unique insights essential for understanding drug mechanisms and optimizing development.