Abstract

Contractile and Electrophysiological Detection of Drug-Induced Cardiotoxicity Using Integrated Silicon Technologies

Thomas Pauwelyn, PhD Researcher, IMEC/KU Leuven Belgium

Drug attrition caused by (cardio)toxicity is a major risk that pharmaceutical industry faces today [1]. Besides relevant human-derived cell models, better tools are needed to increase predictability of attrition. In the heart, monitoring both electrophysiological [2] and contractile [3] parameters is required to determine the sensitivity to adverse drug effects. Although microfluidic heart-on-a-chip devices [4,5] have been reported for cardiotoxicity screening purposes, there is room for improvement in integrating sensors. Silicon technology is known to leverage miniaturization, integration and cost-effective scaling. Here, we present silicon-based sensor technology for imaging contractile events and detecting electrical activity of cardiac cells. We used lens-free imaging (LFI) to detect contractile parameters such as contraction and relaxation length and strength with a 19-times larger field of view compared to phase contrast microscopy. This also allowed to detect conduction speed and patterns in cardiac monolayers. Further, we employed high-density silicon multi-electrode arrays (MEA) for single-cell action potential detection. Both LFI and MEA assays can also be used to demonstrate interaction of electrophysiological and contractile parameters of the same cells. Finally we demonstrated adverse effects of verapamil and dofetilide on cardiac cells using both systems. Silicon sensor technology thus holds a great future for implementation in organ-on-a-chip devices.