RT Journal Article SR Electronic T1 OptoDyCE: Automated System for High-Throughput All-Optical Dynamic Cardiac Electrophysiology JF bioRxiv FD Cold Spring Harbor Laboratory SP 023572 DO 10.1101/023572 A1 Aleksandra Klimas A1 Jinzhu Yu A1 Christina M. Ambrosi A1 John C. Williams A1 Harold Bien A1 Emilia Entcheva YR 2015 UL http://biorxiv.org/content/early/2015/07/31/023572.1.abstract AB The improvement of preclinical cardiotoxicity testing, the discovery of new ion-channel-targeted drugs, and the phenotyping and use of stem-cell-derived cardiomyocytes and other biologics all necessitate high-throughput (HT), cellular-level electrophysiological interrogation tools. Optical techniques for actuation and sensing provide instant parallelism, enabling contactless dynamic HT testing of cells and small-tissue constructs, not affordable by other means. Here, we consider, computationally and experimentally, the limits of all-optical electrophysiology when applied to drug testing, then implement and validate OptoDyCE, a fully automated system for all-optical cardiac electrophysiology. We validate optical actuation by virally introducing optogenetic drivers in (rat and human) cardiomyocytes or through the modular use of dedicated light-sensitive somatic “spark” cells. We show that this automated all-optical approach provides high-throughput means of cellular interrogation, i.e. allows for dynamic testing of >600 multicellular samples or compounds per hour, and yields high-content information about the action of a drug over time, space and doses.