High Throughput Screening Challenges

What you need to know

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There has been a recent emphasis in the design and development of increasingly efficient and reliable HTS platforms for early phase drug discovery. In this whitepaper, we will:

  • Outline some of the historical and contemporary strategies of cell-based HTS.
  • Describe some of the technical challenges to overcome in successful HTS methods.
  • Discuss some of the critical statistical concerns in HTS platforms, including common problems.

Technical challenges of cell-based HTS

There are significant technical challenges encountered in HTS that are unique to cellbased approaches as compared to more simplified biochemical assays. In particular is the use of cell lines that stably express a protein of interest, as this method is inherently difficult because it is a challenge to control expression levels after multiple passages.

Moreover, certain types of proteins can be more problematic than others to maintain adequate and reliable expression levels, including ion channels, certain GPCRs and proteins involved in cell death pathways that are maintained at low levels naturally. Some researchers combat this by freezing down large batches of cells to try and maintain consistent expression throughout the duration of the HTS run. However, there can be additional challenges in trying to maintain reliable expression with regard to growth conditions.

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