Organs-on-Chips with combined multi-electrode array and transepithelial electrical resistance measurement capabilities

Ben M. Maoz, Anna Herland, Olivier Y.F. Henry, William D. Leineweber, Moran Yadid, John Doyle, Robert Mannix, Ville J. Kujala, Edward A. Fitzgerald, Kevin Kit Parker, Donald E. Ingber

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

Here we demonstrate that microfluidic cell culture devices, known as Organs-on-a-Chips can be fabricated with multifunctional, real-time, sensing capabilities by integrating both multi-electrode arrays (MEAs) and electrodes for transepithelial electrical resistance (TEER) measurements into the chips during their fabrication. To prove proof-of-concept, simultaneous measurements of cellular electrical activity and tissue barrier function were carried out in a dual channel, endothelialized, heart-on-a-chip device containing human cardiomyocytes and a channel-separating porous membrane covered with a primary human endothelial cell monolayer. These studies confirmed that the TEER-MEA chip can be used to simultaneously detect dynamic alterations of vascular permeability and cardiac function in the same chip when challenged with the inflammatory stimulus tumor necrosis factor alpha (TNF-α) or the cardiac targeting drug isoproterenol. Thus, this Organ Chip with integrated sensing capability may prove useful for real-time assessment of biological functions, as well as response to therapeutics.

Original languageEnglish
Pages (from-to)2294-2302
Number of pages9
JournalLab on a Chip
Volume17
Issue number13
DOIs
StatePublished - 27 Jun 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Royal Society of Chemistry.

Funding

This research was sponsored by the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Defense Advanced Research Projects Agency under Cooperative Agreement Number W911NF-12-2-0036. 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 Defense Advanced Research Projects Agency, or the U.S. Government. This work was performed in part at the Center for Nanoscale System (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. We acknowledge the technical assistance of M. Rosnach and B. Fountaine.

FundersFunder number
National Science Foundation1541959
Defense Advanced Research Projects AgencyW911NF-12-2-0036
Harvard University
Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University

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