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Adapting Cell-Based Assays to the High Throughput Screening Platform: Problems Encountered and Lessons Learned.
JALA (Charlottesville, Va.)
|June 4, 2009
Summary
Cell-based phenotypic assays offer robust drug discovery screening. This study addresses common implementation challenges, providing solutions for consistent and reliable high throughput screening (HTS) results.
Area of Science:
- Biochemistry
- Cell Biology
- Drug Discovery
Background:
- Biochemical target-based assays were previously dominant in drug discovery.
- Cell-based phenotypic assays are emerging as a powerful screening technology.
- Stem cell-based screening requires careful consideration of HTS adaptation challenges.
Purpose of the Study:
- To overview challenges in implementing cell-based assays for high throughput screening (HTS).
- To present empirically defined solutions for common HTS problems.
- To ensure assay consistency and reliability in drug discovery.
Main Methods:
- Implementation of multiple cell-based assays at a High Throughput Screening Center.
- Empirical investigation of artifacts induced by environmental factors.
- Analysis of cell plating conditions, DMSO carry-over, and incubator effects.
Main Results:
- Identified artifacts from temperature variations during screening campaigns.
- Demonstrated impact of cell plating conditions and room temperature incubation on assay consistency.
- Characterized incubator-induced artifacts and DMSO carry-over issues.
Conclusions:
- Successful implementation of cell-based assays in HTS requires addressing specific technical challenges.
- Empirical solutions are crucial for mitigating artifacts and ensuring assay robustness.
- Optimized protocols enhance the reliability of cell-based phenotypic screening for drug discovery.
