Jul 31, 2015

OptoDyCE: Automated System for High-Throughput All-Optical Dynamic Cardiac Electrophysiology

BioRxiv : the Preprint Server for Biology
Aleksandra KlimasEmilia Entcheva

Abstract

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.

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Mentioned in this Paper

Biological Products
Substance Abuse Detection
Anatomical Space Structure
Ion Channel
Pharmacologic Substance
High Throughput Analysis
Electrophysiology (Science)
Optogenetics
Compound (Substance)
Cardiac Electrophysiology

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