Cell–cell communication plays a pivotal role in biological systems’ coordination and function. Electrical properties have been linked to specification and differentiation of stem cells into targeted progeny, such as neurons and cardiomyocytes. Currently, there is a critical need in developing new ways to complement fluorescent indicators, such as Ca2+-sensitive dyes, for direct electrophysiological measurements of cells and tissue. Here, we report a unique transparent and biocompatible graphene-based electrical platform that enables electrical and optical investigation of human embryonic stem cell-derived cardiomyocytes’ (hESC-CMs) intracellular processes and intercellular communication.
Graphene, a honeycomb sp2 hybridized two-dimensional carbon lattice, was synthesized using low pressure chemical vapor deposition system, and was tested for biocompatibility. Au and graphene microelectrode arrays (MEAs) were fabricated using well-established microfabrication methods. Au and graphene MEAs were interfaced with hESC-CMs to perform both optical and electrical recordings.
Optical imaging and Raman spectroscopy confirmed the presence of monolayer graphene. Viability assay showed biocompatibility of graphene. Electrochemical characterization proved graphene’s functional activity. Nitric acid treatment further enhanced the electrochemical properties of graphene. Graphene electrodes’ transparency enabled both optical and electrical recordings from hESC-CMs. Graphene MEA detected changes in beating frequency and field potential duration upon β-adrenergic receptor agonist treatment.
The transparent graphene platform enables the investigation of both intracellular and intercellular communication processes and will create new avenues for bidirectional communication (sensing and stimulation) with electrically active tissues and will set the ground for investigations reported diseases such as Alzheimer, Parkinson’s disease and arrhythmias.
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T. Cohen-Karni would like to thank the National Science Foundation (CBET1552833) and the Office of Naval Research (N000141712368). The authors would also like to thank Carnegie Mellon University Nanofabrication Facility, and the Department of Materials Science and Engineering Materials Characterization Facility (MCF).
Conflict of interest
Sahil K. Rastogi, Jacqueline Bliley, Daniel J. Shiwarski, Guruprasad Raghavan, Adam W. Feinberg and Tzahi Cohen-Karni declare that they have no conflicts of interest.
No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.
Tzahi Cohen-Karni is an assistant professor at the departments of Biomedical Engineering and Materials Science and Engineering in Carnegie Mellon University, Pittsburgh PA USA. He received both his B.Sc. degree in Materials Engineering and the B.A. degree in Chemistry from the Technion Israel Institute of Technology, Haifa, Israel, in 2004. His M.Sc. degree in Chemistry from Weizmann Institute of Science, Rehovot, Israel, in 2006 and his Ph.D. in Applied Physics from the School of Engineering and Applied Sciences, Harvard University, Cambridge MA, USA, in 2011. He was a Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellow at the Massachusetts Institute of Technology and Boston Children’s Hospital at the labs of Robert Langer and Daniel S. Kohane from 2011 to 2013. Dr. Cohen-Karni received the Gold Graduate Student Award from the Materials Research Society in 2009, and received the 2012 International Union of Pure and Applied Chemistry Young Chemist Award. In 2014, he was awarded the Charles E. Kaufman Foundation Young Investigator Research Award. In 2016, Dr. Cohen-Karni was awarded the NSF CAREER Award. In 2017, Dr. Cohen-Karni was awarded the Cellular and Molecular Bioengineering Rising Star Award, The Office of Naval Research Young Investigator Award and The George Tallman Ladd Research Award.
This article is part of the 2018 CMBE Young Innovators special issue.
Associate Editor William E. Bentley oversaw the review of this article.
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Rastogi, S.K., Bliley, J., Shiwarski, D.J. et al. Graphene Microelectrode Arrays for Electrical and Optical Measurements of Human Stem Cell-Derived Cardiomyocytes. Cel. Mol. Bioeng. 11, 407–418 (2018). https://doi.org/10.1007/s12195-018-0525-z
- Transparent electrodes
- Calcium imaging
- High spatial and temporal resolution