Novel Data Analysis for in Vitro Electrophysiological Assays in HTS

Recent development in automated patch-clamp platforms has transformed the preclinical drug development landscape by incorporating electrophysiological assays at early stages of drug screening. PatchXpress 7000A, an automated 16-channel parallel patch-clamp platform, has a higher throughput than the conventional whole cell patch clamp. We developed and optimized assay conditions for the human ether-a-go-go channel (hERG) on an automated patch-clamp system such as PatchXpress 7000A. We applied nonlinear mixed models to quantify the consistency of the assay from cell to cell and to provide an accurate measure of drug potency over the population of the same cell type. The well-known hERG blocker quinidine was used in the experiments. The results of this novel statistical approach are the estimate of the average potency for the population of the cells with high degree of accuracy and the estimate of the potency variability from cell to cell. This method revealed no significant difference in the potency estimates for our assay and for conventional patch-clamp platform. We suggest that the novel data analysis can accurately predict compound potency when the assay protocols may have a small number of test concentrations and repeated measurements. (JALA 2006;11:195–202)