title: OptoDyCE as an automated system for high-throughput all-optical dynamic cardiac electrophysiology.
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.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimas
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ambrosi
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Jinzhu
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
authors.forename: John C
authors.identifier: 0000-0002-3500-914X
authors.initials: JC
authors.lastname: Williams
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Harold
authors.identifier: 0000-0002-4352-1848
authors.initials: H
authors.lastname: Bien
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Emilia
authors.initials: E
authors.lastname: Entcheva
mesh_terms: D000818:Animals; D001331:Automation; D054715:Cardiotoxins / Q000633:toxicity; D002478:Cells, Cultured; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000008:administration & dosage / Q000633:toxicity; D062308:Optogenetics / Q000379:methods*; D051381:Rats
chemical_list: D054715:Cardiotoxins; D009543:Nifedipine