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Title: Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions and under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.
Authors:
ORCiD logo [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1] ;  [1] ;  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States). Dept. of Medicine
Publication Date:
Report Number(s):
LLNL-JRNL-714498
Journal ID: ISSN 1473-0197; LCAHAM
Grant/Contract Number:
AC52-07NA27344
Type:
Accepted Manuscript
Journal Name:
Lab on a chip (Print)
Additional Journal Information:
Journal Name: Lab on a chip (Print); Journal Volume: 17; Journal Issue: 10; Journal ID: ISSN 1473-0197
Publisher:
Royal Society of Chemistry
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
OSTI Identifier:
1361595