Characterization of hERG blockers using the automated QPatch 16 screening system

著者: Rasmus B Jacobsen, Simon Pedersen, Søren Friis, Nicoline Andersen, Niels Willumsen

The QPatch™ technology has been developed to significantly increase throughput in ion channel drug screening. It is based on planar glass-coated silicon chips with micro-etched patch-clamp holes. Extra andintracellular Ringer solutions are applied by miniature flow channels, which ensures laminar flow and short fluid exchange times (<100 ms). The walls of the flow channels are covered with non-polymer materials (glass and silicon) to minimize problems with non-specific binding of ‘sticky’ compounds. Below is shown the QPatch-16, the first instrument based on the QPatch technology. It runs 16 parallel whole-cell patch-clamp experiments simultaneously with success rates of 50-80 %. Cells are maintained in growth medium in an onboard cell storage facility for up to 4 hours until shortly before an experiment. At that time they are automatically spun down in a miniature centrifuge, washed, and resuspended in Ringer’s solution before being applied to the patch-clamp site. We have determined the IC50 values for 32 hERG channel blockers in a blind test and made a comparison with IC50 values obtained in conventional
manual patch-clamp.