On-chip pre-clinical cardiac toxicity: Testing compounds beyond herg and qt using hES/hiPS cardiomyocyte re-entry cell network model on a chip

Limitation of conventional hERG assay and QT prolongation testing for accurate prediction of Torsades de Pointes (TdP) by compounds unvailed us the necesity of new approach to evaluate global cardiac safety. On-chip re-entry cell network model assay has the potential to measure the TdP probability as pre-clinical testing for cardiac safety by the single cell-based optical/electrical measurement of the heart pressure, Na, K, Ca ion channel conditions and their fluctuations. The application of ion channel inhibitors resulted in dose-dependent changes to the field potential waveform, and these changes were identical to those induced in the native cardiomyocytes. This study shows that on-chip model represent a promising in vitro assay for cardiac toxicity and drug screening.