Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384


ICMS 2018 UK


David J. Standing, Kelly Gatfield, David L. Downie, Metul Patel, Andrew J. Brown



hERG (human Ether-a go-go-Related Gene) is a voltage-gated ion channel expressed in cardiac tissue which is of particular concern in off-target pharmacology. Blockade of hERG can lead to prolongation of cardiac repolarisation (long QT syndrome) and ventricular arrhythmia (torsades de pointes). Drug-induced LQTS is the most common reason for drug withdrawal in the last ten years; techniques are therefore required to address this and help to reduce attrition as early as possible in the drug development process.

Second generation automated electrophysiology systems such as IonWorks Barracuda use perforated patch technology to allow c.600 dose-response curves to be generated per day, but produce low fidelity megaOhm recordings with poor success rates. We have developed a more robust, reproducible high throughput whole-cell patch clamp assay methodology using the Sophion Qube 384, which provides higher fidelity
recordings and improved reliability in prediction of activity compared to other automated electrophysiology methods

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