Classifying the Electrophysiological Effects of Chronotropic Drugs on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes using Voltage Sensitive Dyes and Supervised Machine Learning

• DOI: 10.1016/j.bpj.2014.11.624
• Publication Date: 2015-01-27T12:50:23Z
• Authors: Christopher M. He...; Rupsa Datta; Bruce R. Conklin; Steven C. George; Enrico Gratton
• Keywords: Physical Sciences; Chemical Sciences; Biophysics; 0202 electrical engineering, electronic engineering, information engineering; 02 engineering and technology; Biological Sciences

The emergence of human induced pluripotent stem (hiPS) cell technology has expanded the possibilities for sourcing human cardiomyocytes (hiPS-CMs). Novel microscopy and analysis methods serve to accelerate development and validation of in vitro hiPS-CM models for drug screening. Voltage sensitive dyes (VSD) allow non-invasive, non-destructive, and longitudinal assessment of hiPS-CM electrophysiology at the sub-cellular membrane scale. In this study, we successfully use 2-photon microscopy to capture VSD signal at the cellular membrane scale generated from actively beating hiPS-CMs exposed to the chronotropic drugs, propranolol (10−5 M) and isoproterenol (10−7 M).