Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

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.

doi:10.1039/C7LC00210F

Title: Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

Journal Article · Tue Apr 18 00:00:00 EDT 2017 · Lab on a Chip

DOI:https://doi.org/10.1039/C7LC00210F· OSTI ID:1361595

^[1]; Huang, Chao ^[1]; Lin, Yi-Dong ^[2]; Ivanovskaya, Anna N. ^[1]; O'Hara, Thomas J. ^[1]; Booth, Ross H. ^[1]; Creek, Cameron J. ^[1]; Enright, Heather A. ^[1]; Soscia, David A. ^[1]; Belle, Anna M. ^[1]; Liao, Ronglih ^[2]; Lightstone, Felice C. ^[1]; Kulp, Kristen S. ^[1]; Wheeler, Elizabeth K. ^[1]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States). Dept. of Medicine

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.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1361595

Report Number(s):: LLNL-JRNL-714498; LCAHAM

Journal Information:: Lab on a Chip, Vol. 17, Issue 10; ISSN 1473-0197

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 77 works

Citation information provided by
Web of Science

References (38)

Human Stem Cell-Derived Cardiomyocytes in Cellular Impedance Assays: Bringing Cardiotoxicity Screening to the Front Line Peters, Matthew F.; Lamore, Sarah D.; Guo, Liang Cardiovascular Toxicology, Vol. 15, Issue 2 https://doi.org/10.1007/s12012-014-9268-9	journal	August 2014
Image-based evaluation of contraction–relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology Hayakawa, Tomohiro; Kunihiro, Takeshi; Ando, Tomoko Journal of Molecular and Cellular Cardiology, Vol. 77 https://doi.org/10.1016/j.yjmcc.2014.09.010	journal	December 2014
Theoretical and experimental determination of cell constants of planar-interdigitated electrolyte conductivity sensors Olthuis, W.; Streekstra, W.; Bergveld, P. Sensors and Actuators B: Chemical, Vol. 24, Issue 1-3 https://doi.org/10.1016/0925-4005(95)85053-8	journal	March 1995
Dual effects of norepinephrine and mechanisms of baroreceptor stimulation. Munch, P. A.; Thoren, P. N.; Brown, A. M. Circulation Research, Vol. 61, Issue 3 https://doi.org/10.1161/01.RES.61.3.409	journal	September 1987
Electromechanical integration of cardiomyocytes derived from human embryonic stem cells Kehat, Izhak; Khimovich, Leonid; Caspi, Oren Nature Biotechnology, Vol. 22, Issue 10 https://doi.org/10.1038/nbt1014	journal	September 2004
Local control of β-adrenergic stimulation: Effects on ventricular myocyte electrophysiology and Ca2+-transient Heijman, Jordi; Volders, Paul G. A.; Westra, Ronald L. Journal of Molecular and Cellular Cardiology, Vol. 50, Issue 5 https://doi.org/10.1016/j.yjmcc.2011.02.007	journal	May 2011
Disorder in Excitation-Contraction Coupling of Cardiac Muscle from Cats with Experimentally Produced Right Ventricular Hypertrophy Kaufmann, Raimund L.; Homburger, Hermann; Wirth, Heike Circulation Research, Vol. 28, Issue 3 https://doi.org/10.1161/01.RES.28.3.346	journal	March 1971
A cardiomyocyte-based biosensor for antiarrhythmic drug evaluation by simultaneously monitoring cell growth and beating Wang, Tianxing; Hu, Ning; Cao, Jiayue Biosensors and Bioelectronics, Vol. 49 https://doi.org/10.1016/j.bios.2013.04.039	journal	November 2013
A Non-invasive Platform for Functional Characterization of Stem-Cell-Derived Cardiomyocytes with Applications in Cardiotoxicity Testing Maddah, Mahnaz; Heidmann, Julia D.; Mandegar, Mohammad A. Stem Cell Reports, Vol. 4, Issue 4 https://doi.org/10.1016/j.stemcr.2015.02.007	journal	April 2015
Physical developmental cues for the maturation of human pluripotent stem cell-derived cardiomyocytes Zhu, Renjun; Blazeski, Adriana; Poon, Ellen Stem Cell Research & Therapy, Vol. 5, Issue 5 https://doi.org/10.1186/scrt507	journal	January 2014
Measuring the Contractile Forces of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes With Arrays of Microposts Rodriguez, Marita L.; Graham, Brandon T.; Pabon, Lil M. Journal of Biomechanical Engineering, Vol. 136, Issue 5 https://doi.org/10.1115/1.4027145	journal	April 2014
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 Sirenko, Syevda; Maltsev, Victor A.; Maltseva, Larissa A. Journal of Molecular and Cellular Cardiology, Vol. 66 https://doi.org/10.1016/j.yjmcc.2013.11.011	journal	January 2014
Dynamic monitoring of beating periodicity of stem cell-derived cardiomyocytes as a predictive tool for preclinical safety assessment: Microelectronic monitoring of functional cardiotoxicity Abassi, Yama A.; Xi, Biao; Li, Nan British Journal of Pharmacology, Vol. 165, Issue 5 https://doi.org/10.1111/j.1476-5381.2011.01623.x	journal	February 2012
Microsystems for biomimetic stimulation of cardiac cells Simmons, Chelsey S.; Petzold, Bryan C.; Pruitt, Beth L. Lab on a Chip, Vol. 12, Issue 18 https://doi.org/10.1039/c2lc40308k	journal	January 2012
Impedance-Based Detection of Beating Rhythm and Proarrhythmic Effects of Compounds on Stem Cell-Derived Cardiomyocytes Jonsson, Malin K. B.; Wang, Qing-Dong; Becker, Bruno ASSAY and Drug Development Technologies, Vol. 9, Issue 6 https://doi.org/10.1089/adt.2011.0396	journal	December 2011
Impedance-Based Monitoring of Ongoing Cardiomyocyte Death Induced by Tumor Necrosis Factor-α Qiu, Yiling; Liao, Ronglih; Zhang, Xin Biophysical Journal, Vol. 96, Issue 5 https://doi.org/10.1016/j.bpj.2008.11.036	journal	March 2009
The Effect of Norepinephrine on Cardiac Output, Arterial Blood Pressure, and Heart rate in dogs Treated with Chlorothiazide*† Eckstein, John W.; Abboud, Francois M.; Pereda, Santiago A. Journal of Clinical Investigation, Vol. 41, Issue 8 https://doi.org/10.1172/JCI104615	journal	August 1962
Cardiomyocyte Differentiation of Human Induced Pluripotent Stem Cells Zwi, Limor; Caspi, Oren; Arbel, Gil Circulation, Vol. 120, Issue 15 https://doi.org/10.1161/CIRCULATIONAHA.109.868885	journal	October 2009
Organs-on-chips at the frontiers of drug discovery Esch, Eric W.; Bahinski, Anthony; Huh, Dongeun Nature Reviews Drug Discovery, Vol. 14, Issue 4 https://doi.org/10.1038/nrd4539	journal	March 2015
Human induced pluripotent stem cell-based microphysiological tissue models of myocardium and liver for drug development Mathur, Anurag; Loskill, Peter; Hong, SoonGweon Stem Cell Research & Therapy, Vol. 4, Issue Suppl 1 https://doi.org/10.1186/scrt375	journal	January 2013
Defective Excitation-Contraction Coupling in Experimental Cardiac Hypertrophy and Heart Failure Gomez, A. M. Science, Vol. 276, Issue 5313 https://doi.org/10.1126/science.276.5313.800	journal	May 1997
In vitro cardiac tissue models: Current status and future prospects Mathur, Anurag; Ma, Zhen; Loskill, Peter Advanced Drug Delivery Reviews, Vol. 96 https://doi.org/10.1016/j.addr.2015.09.011	journal	January 2016
*In vitro* Model for Assessing Arrhythmogenic Properties of Drugs Based on High-resolution Impedance Measurements Nguemo, Filomain; aric, Tomo; Pfannkuche, Kurt Cellular Physiology and Biochemistry, Vol. 29, Issue 5-6 https://doi.org/10.1159/000188069	journal	January 2012
Bridging Functional and Structural Cardiotoxicity Assays Using Human Embryonic Stem Cell-Derived Cardiomyocytes for a More Comprehensive Risk Assessment Clements, Mike; Millar, Val; Williams, Angela S. Toxicological Sciences, Vol. 148, Issue 1 https://doi.org/10.1093/toxsci/kfv180	journal	August 2015
Impedance Characterization and Modeling of Electrodes for Biomedical Applications Franks, W.; Schenker, I.; Schmutz, P. IEEE Transactions on Biomedical Engineering, Vol. 52, Issue 7 https://doi.org/10.1109/TBME.2005.847523	journal	July 2005
Scalable Electrophysiological Investigation of iPS Cell-Derived Cardiomyocytes Obtained by a Lentiviral Purification Strategy Friedrichs, Stephanie; Malan, Daniela; Voss, Yvonne Journal of Clinical Medicine, Vol. 4, Issue 1 https://doi.org/10.3390/jcm4010102	journal	January 2015
Intracellular recording of action potentials by nanopillar electroporation Xie, Chong; Lin, Ziliang; Hanson, Lindsey Nature Nanotechnology, Vol. 7, Issue 3 https://doi.org/10.1038/nnano.2012.8	journal	February 2012
Structural heterogeneity promotes triggered activity, reflection and arrhythmogenesis in cardiomyocyte monolayers: Tissue structure, early after-depolarizations and reflection Auerbach, David S.; Grzȩda, Krzysztof R.; Furspan, Philip B. The Journal of Physiology, Vol. 589, Issue 9 https://doi.org/10.1113/jphysiol.2010.200576	journal	April 2011
Adrenergic Regulation of HCN4 Channel Requires Protein Association with β ₂ -Adrenergic Receptor Greene, Derek; Kang, Seungwoo; Kosenko, Anastasia Journal of Biological Chemistry, Vol. 287, Issue 28 https://doi.org/10.1074/jbc.M112.366955	journal	May 2012
Blebbistatin: use as inhibitor of muscle contraction Farman, Gerrie P.; Tachampa, Kittipong; Mateja, Ryan Pflügers Archiv - European Journal of Physiology, Vol. 455, Issue 6 https://doi.org/10.1007/s00424-007-0375-3	journal	November 2007
Ensembles of engineered cardiac tissues for physiological and pharmacological study: Heart on a chip Grosberg, Anna; Alford, Patrick W.; McCain, Megan L. Lab on a Chip, Vol. 11, Issue 24 https://doi.org/10.1039/c1lc20557a	journal	January 2011
Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment Zhang, Xiaoyu; Guo, Liang; Zeng, Haoyu Journal of Pharmacological and Toxicological Methods, Vol. 81 https://doi.org/10.1016/j.vascn.2016.06.004	journal	September 2016
Microfluidic organs-on-chips Bhatia, Sangeeta N.; Ingber, Donald E. Nature Biotechnology, Vol. 32, Issue 8 https://doi.org/10.1038/nbt.2989	journal	August 2014
Measuring cell-generated forces: a guide to the available tools Polacheck, William J.; Chen, Christopher S. Nature Methods, Vol. 13, Issue 5 https://doi.org/10.1038/nmeth.3834	journal	April 2016
Cardiac Repolarisation and Drug Regulation: Assessing Cardiac Safety 10 Years after the CPMP Guidance Shah, Rashmi R. Drug Safety, Vol. 30, Issue 12 https://doi.org/10.2165/00002018-200730120-00003	journal	January 2007
Multi-electrode array technologies for neuroscience and cardiology Spira, Micha E.; Hai, Aviad Nature Nanotechnology, Vol. 8, Issue 2 https://doi.org/10.1038/nnano.2012.265	journal	February 2013
Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues Dai, Xiaochuan; Zhou, Wei; Gao, Teng Nature Nanotechnology, Vol. 11, Issue 9 https://doi.org/10.1038/nnano.2016.96	journal	June 2016
Simultaneous Voltage and Calcium Mapping of Genetically Purified Human Induced Pluripotent Stem Cell–Derived Cardiac Myocyte Monolayers Lee, Peter; Klos, Matt; Bollensdorff, Christian Circulation Research, Vol. 110, Issue 12 https://doi.org/10.1161/CIRCRESAHA.111.262535	journal	June 2012

Cited By (8)

High Performance Flexible Organic Electrochemical Transistors for Monitoring Cardiac Action Potential Liang, Yuanying; Ernst, Mathis; Brings, Fabian Advanced Healthcare Materials, Vol. 7, Issue 19 https://doi.org/10.1002/adhm.201800304	journal	August 2018
Engineering anisotropic cardiac monolayers on microelectrode arrays for non-invasive analyses of electrophysiological properties Alassaf, Ahmad; Tansik, Gulistan; Mayo, Vera The Analyst, Vol. 145, Issue 1 https://doi.org/10.1039/c9an01339c	journal	January 2020
Flat and microstructured polymeric membranes in organs-on-chips Pasman, Thijs; Grijpma, Dirk; Stamatialis, Dimitrios Journal of The Royal Society Interface, Vol. 15, Issue 144 https://doi.org/10.1098/rsif.2018.0351	journal	July 2018
Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics McAleer, Christopher W.; Long, Christopher J.; Elbrecht, Daniel Science Translational Medicine, Vol. 11, Issue 497 https://doi.org/10.1126/scitranslmed.aav1386	journal	June 2019
Reflective lens-free imaging on high-density silicon microelectrode arrays for monitoring and evaluation of in vitro cardiac contractility Pauwelyn, Thomas; Stahl, Richard; Mayo, Lakyn Biomedical Optics Express, Vol. 9, Issue 4 https://doi.org/10.1364/boe.9.001827	journal	January 2018
Multi-organ on a chip for personalized precision medicine Palaninathan, Vivekanandan; Kumar, Vimal; Maekawa, Toru MRS Communications, Vol. 8, Issue 03 https://doi.org/10.1557/mrc.2018.148	journal	August 2018
Human-Derived Organ-on-a-Chip for Personalized Drug Development Jodat, Yasamin A.; Kang, Min G.; Kiaee, Kiavash Current Pharmaceutical Design, Vol. 24, Issue 45 https://doi.org/10.2174/1381612825666190308150055	journal	April 2019
Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials Barreto, Sara; Hamel, Leonie; Schiatti, Teresa Cells, Vol. 8, Issue 12 https://doi.org/10.3390/cells8121536	journal	November 2019

Similar Records

Effects of Electrical Stimulation on hiPSC-CM Responses to Classic Ion Channel Blockers

Journal Article · Mon Feb 10 00:00:00 EST 2020 · Toxicological Sciences · OSTI ID:1361595

Wei, Feng; Pourrier, Marc; Strauss, David G.; +2 more

Use of human stem cell derived cardiomyocytes to examine sunitinib mediated cardiotoxicity and electrophysiological alterations

Journal Article · Tue Nov 15 00:00:00 EST 2011 · Toxicology and Applied Pharmacology · OSTI ID:1361595

Mechanisms of QT prolongation by buprenorphine cannot be explained by direct hERG channel block

Journal Article · Fri Nov 06 00:00:00 EST 2020 · PLoS ONE · OSTI ID:1361595

Tran, Phu N.; Sheng, Jiansong; Randolph, Aaron L.; +10 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES

Title: Simultaneous electrical recording of cardiac electrophysiology and contraction on chip

Citation Formats

References (38)

Cited By (8)

Similar Records

Related Subjects