OptoDyCE as an automated system for high-throughput all-optical dynamic cardiac electrophysiology

Aleksandra Klimas, Christina M. Ambrosi, Jinzhu Yu, John C. Williams, Harold Bien and Emilia Entcheva ()
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Aleksandra Klimas: Stony Brook University
Christina M. Ambrosi: Stony Brook University
Jinzhu Yu: Stony Brook University
John C. Williams: Stony Brook University
Harold Bien: Stony Brook University
Emilia Entcheva: Stony Brook University

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract The improvement of preclinical cardiotoxicity testing, discovery of new ion-channel-targeted drugs, and 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 show, 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 HT means of cellular interrogation, that is, 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.

Date: 2016
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DOI: 10.1038/ncomms11542

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