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

Nat Commun. 2016 May 10;7:11542. doi: 10.1038/ncomms11542.

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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Animals
  • Automation
  • Cardiotoxins / toxicity
  • Cells, Cultured
  • Drug Discovery
  • Drug Evaluation, Preclinical / methods
  • Electrophysiologic Techniques, Cardiac / methods*
  • High-Throughput Screening Assays / methods
  • Humans
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Nifedipine / administration & dosage
  • Nifedipine / toxicity
  • Optogenetics / methods*
  • Rats

Substances

  • Cardiotoxins
  • Nifedipine