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Issue 21, 2017
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Cardiac microphysiological devices with flexible thin-film sensors for higher-throughput drug screening

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Abstract

Microphysiological systems and organs-on-chips promise to accelerate biomedical and pharmaceutical research by providing accurate in vitro replicas of human tissue. Aside from addressing the physiological accuracy of the model tissues, there is a pressing need for improving the throughput of these platforms. To do so, scalable data acquisition strategies must be introduced. To this end, we here present an instrumented 24-well plate platform for higher-throughput studies of engineered human stem cell-derived cardiac muscle tissues that recapitulate the laminar structure of the native ventricle. In each well of the platform, an embedded flexible strain gauge provides continuous and non-invasive readout of the contractile stress and beat rate of an engineered cardiac tissue. The sensors are based on micro-cracked titanium–gold thin films, which ensure that the sensors are highly compliant and robust. We demonstrate the value of the platform for toxicology and drug-testing purposes by performing 12 complete dose–response studies of cardiac and cardiotoxic drugs. Additionally, we showcase the ability to couple the cardiac tissues with endothelial barriers. In these studies, which mimic the passage of drugs through the blood vessels to the musculature of the heart, we regulate the temporal onset of cardiac drug responses by modulating endothelial barrier permeability in vitro.

Graphical abstract: Cardiac microphysiological devices with flexible thin-film sensors for higher-throughput drug screening

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Supplementary files

Article information


Submitted
16 Jul 2017
Accepted
22 Sep 2017
First published
28 Sep 2017

Lab Chip, 2017,17, 3692-3703
Article type
Paper

Cardiac microphysiological devices with flexible thin-film sensors for higher-throughput drug screening

J. U. Lind, M. Yadid, I. Perkins, B. B. O'Connor, F. Eweje, C. O. Chantre, M. A. Hemphill, H. Yuan, P. H. Campbell, J. J. Vlassak and K. K. Parker, Lab Chip, 2017, 17, 3692
DOI: 10.1039/C7LC00740J

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