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

Johan U. Lind, Moran Yadid, Ian Perkins, Blakely B. O'Connor, Feyisayo Eweje, Christophe O. Chantre, Matthew A. Hemphill, Hongyan Yuan, Patrick H. Campbell, Joost J. Vlassak, Kevin K. Parker

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

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.

Original languageEnglish
Pages (from-to)3692-3703
Number of pages12
JournalLab on a Chip
Volume17
Issue number21
DOIs
StatePublished - 25 Oct 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Royal Society of Chemistry 2017.

Funding

This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which is supported by the National Science Foundation under NSF award no. 1541959. CNS is part of Harvard University. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UH3TR000522; U. S. Army Research Laboratory and the U. S. Army Research Office under Contract No. W911NF-12-2-0036; and the Harvard University Materials Research Science and Engineering Center (MRSEC), NSF Award number DMR-1420570. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office, Army Research Laboratory, the U.S. Government or the National Institutes of Health. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation hereon. Authors thanks K. Hudson and M. Rosnach for assistance with photography, as well as J. Ferrier and A. Cho for their assistance with 3D rendering and shadow-mask fabrications. Authors additionally thank F. S. Pasqualini, S. P. Sheehy, J. A. Goss, T. A. Busbee and T. Biering-Sorensen for helpful discussions.

FundersFunder number
U. S. Army Research Laboratory
U. S. Army Research OfficeW911NF-12-2-0036
National Science Foundation1541959
National Institutes of Health
National Center for Advancing Translational SciencesUH3TR000522
Materials Research Science and Engineering Center, Harvard UniversityDMR-1420570

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