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Graphene Microelectrode Arrays for Electrical and Optical Measurements of Human Stem Cell-Derived Cardiomyocytes

  • Sahil Kumar Rastogi
  • Jacqueline Bliley
  • Daniel J. Shiwarski
  • Guruprasad Raghavan
  • Adam W. Feinberg
  • Tzahi Cohen-Karni
Article

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

Transparent electrodes Calcium imaging High spatial and temporal resolution Bioelectronics hESC-CM Graphene 

Notes

Acknowledgments

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.

Ethical Approval

No human studies were carried out by the authors for this article. No animal studies were carried out by the authors for this article.

Supplementary material

Supplementary material 1 (MP4 13959 kb)

Supplementary material 2 (MP4 18151 kb)

12195_2018_525_MOESM3_ESM.docx (10.3 mb)
Supplementary material 3 (DOCX 10526 kb)

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Copyright information

© Biomedical Engineering Society 2018

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringCarnegie Mellon UniversityPittsburghUSA
  2. 2.Department of Materials Science and EngineeringCarnegie Mellon UniversityPittsburghUSA
  3. 3.Division of Biology and Biological EngineeringCalifornia Institute of TechnologyPasadenaUSA

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