期刊
ACS NANO
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c04676
关键词
iPSC-cardiomyocytes; carbon nanomaterials; contractility; electrophysiology; drug testing; cardiac arrythmia
类别
资金
- Canadian Institutes of Health Research (CIHR) [453591]
- Hospital for Sick Children
- Canada Research Chairs Program (CRC Tier I)
- Ted Rogers Centre for Heart Research
- SickKids Foundation
- Wasser Family
In this study, a biosensing platform was developed using carbon-based nanomaterials for on-chip and simultaneous measurement of contractility and electrophysiology of cardiomyocytes. The platform was validated for disease modeling and drug testing through evaluation of cardiac functional properties and establishment of an in vitro model of drug-induced cardiac arrhythmia.
Heart beating is triggered by the generation and propagation of action potentials through the myocardium, resulting in the synchronous contraction of cardiomyocytes. This process highlights the importance of electrical and mechanical coordination in organ function. Investigating the pathogenesis of heart diseases and potential therapeutic actions in vitro requires biosensing technologies which allow for longterm and simultaneous measurement of the contractility and electrophysiology of cardiomyocytes. However, the adoption of current biosensing approaches for functional measurement of in vitro cardiac models is hampered by low sensitivity, difficulties in achieving multifunctional detection, and costly manufacturing processes. Leveraging carbon-based nanomaterials, we developed a biosensing platform that is capable of performing onchip and simultaneous measurement of contractility and electrophysiology of human induced pluripotent stem-cell-derived cardiomyocyte (iPSC-CM) monolayers. This platform integrates with a flexible thin-film cantilever embedded with a carbon black (CB)-PDMS strain sensor for high-sensitivity contraction measurement and four pure carbon nanotube (CNT) electrodes for the detection of extracellular field potentials with low electrode impedance. Cardiac functional properties including contractile stress, beating rate, beating rhythm, and extracellular field potential were evaluated to quantify iPSC-CM responses to common cardiotropic agents. In addition, an in vitro model of drug-induced cardiac arrhythmia was established to further validate the platform for disease modeling and drug testing.
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