Strategies for enhancing throughput in ion channel drug screening

著者: Rasmus B. Jacobsen, Naja M. Sørensen, Hervør L. Olsen, M. Sunesen, *Niels J. Willumsen

High information-content screenings based on whole-cell current patch-clamp recordings have become available for ion channel pharmacological research with the development of the QPatch automated patch-clamp technology. A significant increase in system throughput was recently achieved by a tripling of the number of parallel operating patch-clamp sites (from 16 to 48) by the introduction of QPatch HT. In a series of hERG screening studies we have subsequently aimed at increasing the throughput further by reducing the average experimental time consumption associated with each IC50 determination, and by employing alternative calculational algorithms. We have investigated the effect of the following three procedures on effective QPatch throughput:

  1. Application of multiple drugs per cell
  2. Reduction of the duration of the experimental
  3. Estimation of drug potency (IC50) based on a
    single inhibitor concentration