Cardiotoxicity is a major contributor to drug failure during clinical trials and drug withdrawal from the market. For this reason, new drugs must be screened for cardiotoxicity. High-throughput screening can eliminate unsafe drugs very early in a drug development program, so methods of accurate high-throughput cardiotoxicity screening are very desirable. Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are an advantageous platform for drug screening because they provide a renewable source of human cardiomyocytes and can be derived from target patient populations. iPSC-CMs exhibit low internal rectifying potassium current levels, limiting their relevance for adult arrhythmogenesis. To address this, an electrode-based dynamic clamp (EDC) is used to inject current and produce more adult-like electrophysiology in iPSC-CMs. However, EDC is not compatible with high throughput applications.
GW and Cornell inventors developed kits and methods for performing optical dynamic clamp (ODC) that uses light to deliver the current necessary to induce adult-like action morphology in iPSC-CMs in a precise and contactless manner. ODC can be used as a platform for high-throughput cardiotoxicity drug screening.
Figure. Schematic of the optical dynamic clamp (ODC) system.