Simultaneous electrical recording of cardiac electrophysiology and contraction on chip
Abstract
Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions and under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.
- Authors:
-
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States). Dept. of Medicine
- Publication Date:
- Research Org.:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1361595
- Report Number(s):
- LLNL-JRNL-714498
Journal ID: ISSN 1473-0197; LCAHAM
- Grant/Contract Number:
- AC52-07NA27344
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Lab on a Chip
- Additional Journal Information:
- Journal Volume: 17; Journal Issue: 10; Journal ID: ISSN 1473-0197
- Publisher:
- Royal Society of Chemistry
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
Citation Formats
Qian, Fang, Huang, Chao, Lin, Yi-Dong, Ivanovskaya, Anna N., O'Hara, Thomas J., Booth, Ross H., Creek, Cameron J., Enright, Heather A., Soscia, David A., Belle, Anna M., Liao, Ronglih, Lightstone, Felice C., Kulp, Kristen S., and Wheeler, Elizabeth K. Simultaneous electrical recording of cardiac electrophysiology and contraction on chip. United States: N. p., 2017.
Web. doi:10.1039/C7LC00210F.
Qian, Fang, Huang, Chao, Lin, Yi-Dong, Ivanovskaya, Anna N., O'Hara, Thomas J., Booth, Ross H., Creek, Cameron J., Enright, Heather A., Soscia, David A., Belle, Anna M., Liao, Ronglih, Lightstone, Felice C., Kulp, Kristen S., & Wheeler, Elizabeth K. Simultaneous electrical recording of cardiac electrophysiology and contraction on chip. United States. https://doi.org/10.1039/C7LC00210F
Qian, Fang, Huang, Chao, Lin, Yi-Dong, Ivanovskaya, Anna N., O'Hara, Thomas J., Booth, Ross H., Creek, Cameron J., Enright, Heather A., Soscia, David A., Belle, Anna M., Liao, Ronglih, Lightstone, Felice C., Kulp, Kristen S., and Wheeler, Elizabeth K. Tue .
"Simultaneous electrical recording of cardiac electrophysiology and contraction on chip". United States. https://doi.org/10.1039/C7LC00210F. https://www.osti.gov/servlets/purl/1361595.
@article{osti_1361595,
title = {Simultaneous electrical recording of cardiac electrophysiology and contraction on chip},
author = {Qian, Fang and Huang, Chao and Lin, Yi-Dong and Ivanovskaya, Anna N. and O'Hara, Thomas J. and Booth, Ross H. and Creek, Cameron J. and Enright, Heather A. and Soscia, David A. and Belle, Anna M. and Liao, Ronglih and Lightstone, Felice C. and Kulp, Kristen S. and Wheeler, Elizabeth K.},
abstractNote = {Prevailing commercialized cardiac platforms for in vitro drug development utilize planar microelectrode arrays to map action potentials, or impedance sensing to record contraction in real time, but cannot record both functions on the same chip with high spatial resolution. We report a novel cardiac platform that can record cardiac tissue adhesion, electrophysiology, and contractility on the same chip. The platform integrates two independent yet interpenetrating sensor arrays: a microelectrode array for field potential readouts and an interdigitated electrode array for impedance readouts. Together, these arrays provide real-time, non-invasive data acquisition of both cardiac electrophysiology and contractility under physiological conditions and under drug stimuli. Furthermore, we cultured human induced pluripotent stem cell-derived cardiomyocytes as a model system, and used to validate the platform with an excitation–contraction decoupling chemical. Preliminary data using the platform to investigate the effect of the drug norepinephrine are combined with computational efforts. Finally, this platform provides a quantitative and predictive assay system that can potentially be used for comprehensive assessment of cardiac toxicity earlier in the drug discovery process.},
doi = {10.1039/C7LC00210F},
journal = {Lab on a Chip},
number = 10,
volume = 17,
place = {United States},
year = {Tue Apr 18 00:00:00 EDT 2017},
month = {Tue Apr 18 00:00:00 EDT 2017}
}
Web of Science
Works referenced in this record:
Human Stem Cell-Derived Cardiomyocytes in Cellular Impedance Assays: Bringing Cardiotoxicity Screening to the Front Line
journal, August 2014
- Peters, Matthew F.; Lamore, Sarah D.; Guo, Liang
- Cardiovascular Toxicology, Vol. 15, Issue 2
Image-based evaluation of contraction–relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology
journal, December 2014
- Hayakawa, Tomohiro; Kunihiro, Takeshi; Ando, Tomoko
- Journal of Molecular and Cellular Cardiology, Vol. 77
Theoretical and experimental determination of cell constants of planar-interdigitated electrolyte conductivity sensors
journal, March 1995
- Olthuis, W.; Streekstra, W.; Bergveld, P.
- Sensors and Actuators B: Chemical, Vol. 24, Issue 1-3
Dual effects of norepinephrine and mechanisms of baroreceptor stimulation.
journal, September 1987
- Munch, P. A.; Thoren, P. N.; Brown, A. M.
- Circulation Research, Vol. 61, Issue 3
Electromechanical integration of cardiomyocytes derived from human embryonic stem cells
journal, September 2004
- Kehat, Izhak; Khimovich, Leonid; Caspi, Oren
- Nature Biotechnology, Vol. 22, Issue 10
Local control of β-adrenergic stimulation: Effects on ventricular myocyte electrophysiology and Ca2+-transient
journal, May 2011
- Heijman, Jordi; Volders, Paul G. A.; Westra, Ronald L.
- Journal of Molecular and Cellular Cardiology, Vol. 50, Issue 5
Disorder in Excitation-Contraction Coupling of Cardiac Muscle from Cats with Experimentally Produced Right Ventricular Hypertrophy
journal, March 1971
- Kaufmann, Raimund L.; Homburger, Hermann; Wirth, Heike
- Circulation Research, Vol. 28, Issue 3
A cardiomyocyte-based biosensor for antiarrhythmic drug evaluation by simultaneously monitoring cell growth and beating
journal, November 2013
- Wang, Tianxing; Hu, Ning; Cao, Jiayue
- Biosensors and Bioelectronics, Vol. 49
A Non-invasive Platform for Functional Characterization of Stem-Cell-Derived Cardiomyocytes with Applications in Cardiotoxicity Testing
journal, April 2015
- Maddah, Mahnaz; Heidmann, Julia D.; Mandegar, Mohammad A.
- Stem Cell Reports, Vol. 4, Issue 4
Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes
journal, January 2014
- Zhu, Renjun; Blazeski, Adriana; Poon, Ellen
- Stem Cell Research & Therapy, Vol. 5, Issue 5
Measuring the Contractile Forces of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes With Arrays of Microposts
journal, April 2014
- Rodriguez, Marita L.; Graham, Brandon T.; Pabon, Lil M.
- Journal of Biomechanical Engineering, Vol. 136, Issue 5
Sarcoplasmic reticulum Ca2+ cycling protein phosphorylation in a physiologic Ca2+ milieu unleashes a high-power, rhythmic Ca2+ clock in ventricular myocytes: Relevance to arrhythmias and bio-pacemaker design
journal, January 2014
- Sirenko, Syevda; Maltsev, Victor A.; Maltseva, Larissa A.
- Journal of Molecular and Cellular Cardiology, Vol. 66
Dynamic monitoring of beating periodicity of stem cell-derived cardiomyocytes as a predictive tool for preclinical safety assessment: Microelectronic monitoring of functional cardiotoxicity
journal, February 2012
- Abassi, Yama A.; Xi, Biao; Li, Nan
- British Journal of Pharmacology, Vol. 165, Issue 5
Microsystems for biomimetic stimulation of cardiac cells
journal, January 2012
- Simmons, Chelsey S.; Petzold, Bryan C.; Pruitt, Beth L.
- Lab on a Chip, Vol. 12, Issue 18
Impedance-Based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell-Derived Cardiomyocytes
journal, December 2011
- Jonsson, Malin K. B.; Wang, Qing-Dong; Becker, Bruno
- ASSAY and Drug Development Technologies, Vol. 9, Issue 6
Impedance-Based Monitoring of Ongoing Cardiomyocyte Death Induced by Tumor Necrosis Factor-α
journal, March 2009
- Qiu, Yiling; Liao, Ronglih; Zhang, Xin
- Biophysical Journal, Vol. 96, Issue 5
The Effect of Norepinephrine on Cardiac Output, Arterial Blood Pressure, and Heart rate in dogs Treated with Chlorothiazide*†
journal, August 1962
- Eckstein, John W.; Abboud, Francois M.; Pereda, Santiago A.
- Journal of Clinical Investigation, Vol. 41, Issue 8
Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells
journal, October 2009
- Zwi, Limor; Caspi, Oren; Arbel, Gil
- Circulation, Vol. 120, Issue 15
Organs-on-chips at the frontiers of drug discovery
journal, March 2015
- Esch, Eric W.; Bahinski, Anthony; Huh, Dongeun
- Nature Reviews Drug Discovery, Vol. 14, Issue 4
Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development
journal, January 2013
- Mathur, Anurag; Loskill, Peter; Hong, SoonGweon
- Stem Cell Research & Therapy, Vol. 4, Issue Suppl 1
Defective Excitation-Contraction Coupling in Experimental Cardiac Hypertrophy and Heart Failure
journal, May 1997
- Gomez, A. M.
- Science, Vol. 276, Issue 5313
In vitro cardiac tissue models: Current status and future prospects
journal, January 2016
- Mathur, Anurag; Ma, Zhen; Loskill, Peter
- Advanced Drug Delivery Reviews, Vol. 96
In vitro Model for Assessing Arrhythmogenic Properties of Drugs Based on High-resolution Impedance Measurements
journal, January 2012
- Nguemo, Filomain; aric, Tomo; Pfannkuche, Kurt
- Cellular Physiology and Biochemistry, Vol. 29, Issue 5-6
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment
journal, August 2015
- Clements, Mike; Millar, Val; Williams, Angela S.
- Toxicological Sciences, Vol. 148, Issue 1
Impedance Characterization and Modeling of Electrodes for Biomedical Applications
journal, July 2005
- Franks, W.; Schenker, I.; Schmutz, P.
- IEEE Transactions on Biomedical Engineering, Vol. 52, Issue 7
Scalable Electrophysiological Investigation of iPS Cell-Derived Cardiomyocytes Obtained by a Lentiviral Purification Strategy
journal, January 2015
- Friedrichs, Stephanie; Malan, Daniela; Voss, Yvonne
- Journal of Clinical Medicine, Vol. 4, Issue 1
Intracellular recording of action potentials by nanopillar electroporation
journal, February 2012
- Xie, Chong; Lin, Ziliang; Hanson, Lindsey
- Nature Nanotechnology, Vol. 7, Issue 3
Structural heterogeneity promotes triggered activity, reflection and arrhythmogenesis in cardiomyocyte monolayers: Tissue structure, early after-depolarizations and reflection
journal, April 2011
- Auerbach, David S.; Grzȩda, Krzysztof R.; Furspan, Philip B.
- The Journal of Physiology, Vol. 589, Issue 9
Adrenergic Regulation of HCN4 Channel Requires Protein Association with β 2 -Adrenergic Receptor
journal, May 2012
- Greene, Derek; Kang, Seungwoo; Kosenko, Anastasia
- Journal of Biological Chemistry, Vol. 287, Issue 28
Blebbistatin: use as inhibitor of muscle contraction
journal, November 2007
- Farman, Gerrie P.; Tachampa, Kittipong; Mateja, Ryan
- Pflügers Archiv - European Journal of Physiology, Vol. 455, Issue 6
Ensembles of engineered cardiac tissues for physiological and pharmacological study: Heart on a chip
journal, January 2011
- Grosberg, Anna; Alford, Patrick W.; McCain, Megan L.
- Lab on a Chip, Vol. 11, Issue 24
Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment
journal, September 2016
- Zhang, Xiaoyu; Guo, Liang; Zeng, Haoyu
- Journal of Pharmacological and Toxicological Methods, Vol. 81
Microfluidic organs-on-chips
journal, August 2014
- Bhatia, Sangeeta N.; Ingber, Donald E.
- Nature Biotechnology, Vol. 32, Issue 8
Measuring cell-generated forces: a guide to the available tools
journal, April 2016
- Polacheck, William J.; Chen, Christopher S.
- Nature Methods, Vol. 13, Issue 5
Cardiac Repolarisation and Drug Regulation: Assessing Cardiac Safety 10 Years after the CPMP Guidance
journal, January 2007
- Shah, Rashmi R.
- Drug Safety, Vol. 30, Issue 12
Multi-electrode array technologies for neuroscience and cardiology
journal, February 2013
- Spira, Micha E.; Hai, Aviad
- Nature Nanotechnology, Vol. 8, Issue 2
Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues
journal, June 2016
- Dai, Xiaochuan; Zhou, Wei; Gao, Teng
- Nature Nanotechnology, Vol. 11, Issue 9
Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell–Derived Cardiac Myocyte Monolayers
journal, June 2012
- Lee, Peter; Klos, Matt; Bollensdorff, Christian
- Circulation Research, Vol. 110, Issue 12
Works referencing / citing this record:
High Performance Flexible Organic Electrochemical Transistors for Monitoring Cardiac Action Potential
journal, August 2018
- Liang, Yuanying; Ernst, Mathis; Brings, Fabian
- Advanced Healthcare Materials, Vol. 7, Issue 19
Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties
journal, January 2020
- Alassaf, Ahmad; Tansik, Gulistan; Mayo, Vera
- The Analyst, Vol. 145, Issue 1
Flat and microstructured polymeric membranes in organs-on-chips
journal, July 2018
- Pasman, Thijs; Grijpma, Dirk; Stamatialis, Dimitrios
- Journal of The Royal Society Interface, Vol. 15, Issue 144
Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics
journal, June 2019
- McAleer, Christopher W.; Long, Christopher J.; Elbrecht, Daniel
- Science Translational Medicine, Vol. 11, Issue 497
Reflective lens-free imaging on high-density silicon microelectrode arrays for monitoring and evaluation of in vitro cardiac contractility
journal, January 2018
- Pauwelyn, Thomas; Stahl, Richard; Mayo, Lakyn
- Biomedical Optics Express, Vol. 9, Issue 4
Multi-organ on a chip for personalized precision medicine
journal, August 2018
- Palaninathan, Vivekanandan; Kumar, Vimal; Maekawa, Toru
- MRS Communications, Vol. 8, Issue 03
Human-Derived Organ-on-a-Chip for Personalized Drug Development
journal, April 2019
- Jodat, Yasamin A.; Kang, Min G.; Kiaee, Kiavash
- Current Pharmaceutical Design, Vol. 24, Issue 45
Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials
journal, November 2019
- Barreto, Sara; Hamel, Leonie; Schiatti, Teresa
- Cells, Vol. 8, Issue 12