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浙江大学学报(工学版)
Journal of ZheJiang University (Engineering Science)  2025, Vol. 59 Issue (8): 1590-1597    DOI: 10.3785/j.issn.1008-973X.2025.08.005
    
Myocardial field potential and conduction monitoring based on flexible printed microelectrode array
Haohang FANG1(),Lingling LIU1,Acan JIANG1,Feng XU1,Changrui ZHANG1,Hang JIN1,Qiang GAO2,Bin LIN2,3,Songyue CHEN1,*(),Daoheng SUN1
1. Pen-Tung Sah Institute of Micro-Nano Science and Technology, Xiamen University, Xiamen 361102, China
2. Guangdong Provincial People’s Hospital, Guangzhou 510080, China
3. Guangdong Beating Origin Regenerative Medicine Limited Company, Foshan 528231, China
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Abstract  

A flexible printed microelectrode array (MEA) system was constructed to develop a platform suitable for field potential monitoring and drug screening of cardiac tissue. The platform was designed to record the electrophysiological activity and excitation conduction of human-derived cardiac tissue. Field potential signals were collected from 16 working electrodes by using a synchronous acquisition function. The analysis of excitation conduction revealed synchronized and rhythmic contractions within the tissue. Drug testing with isoproterenol and verapamil demonstrated the platform’s potential for pharmacological evaluation. These drugs significantly altered contraction frequency, field potential amplitude, and duration.

Key words： microelectrode array      excitation conduction      electrophysiological activity      monitoring platform      drug test     
Received: 11 July 2024      Published: 28 July 2025
CLC:  TP 212  
Fund:  国家自然科学基金资助项目（U2005214）；中国科技部国家重点研发计划资助项目（2022YFB4600600）；翔安创新实验室/传染病疫苗研发全国重点实验室科技资助项目（2023XAKJ0103064）.
Corresponding Authors: Songyue CHEN     E-mail: fanghaohang@stu.xmu.edu.cn;s.chen@xmu.edu.cn
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Articles by authors
Haohang FANG
Lingling LIU
Acan JIANG
Feng XU
Changrui ZHANG
Hang JIN
Qiang GAO
Bin LIN
Songyue CHEN
Daoheng SUN
Cite this article:

Haohang FANG,Lingling LIU,Acan JIANG,Feng XU,Changrui ZHANG,Hang JIN,Qiang GAO,Bin LIN,Songyue CHEN,Daoheng SUN. Myocardial field potential and conduction monitoring based on flexible printed microelectrode array. Journal of ZheJiang University (Engineering Science), 2025, 59(8): 1590-1597.

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https://www.zjujournals.com/eng/10.3785/j.issn.1008-973X.2025.08.005     OR     https://www.zjujournals.com/eng/Y2025/V59/I8/1590


基于柔性印刷微电极阵列的心肌场电位与传导监测

为了构建适用于心肌组织场电位监测与药物筛选的平台，搭建基于柔性印刷的微电极阵列的平台，用于监测人源心肌组织的电生理活动和兴奋传导. 利用同步采集功能，从16个工作电极采集心肌组织的场电位信号. 对心肌组织兴奋传导的分析揭示了心肌组织的同步性和节律性收缩. 通过异丙肾上腺素和维拉帕米的测试，证明了该平台在药物筛选中的应用潜力，这些药物显著影响了心肌组织的收缩频率、场电位幅度与场电位持续时间.


关键词： 微电极阵列,  兴奋传导,  电生理活动,  监测平台,  药物测试 
Fig.1 Design, process and biocompatibility verification of MEA device
Fig.2 Construction of electrophysiological detection platform
Fig.3 Test illustration and performance evaluation of acquisition system of electrophysiological detection platform
Fig.4 Myocardial tissue excitation conduction monitoring
Fig.5 Myocardial tissue field potential under action of different concentration of Isoproterenol
Fig.6 Myocardial tissue field potential under action of different concentration of Verapamil
[1]   DESTERE A, MERINO D, LAVRUT T, et al Drug-induced cardiac toxicity and adverse drug reactions, a narrative review[J]. Therapie, 2024, 79 (2): 161- 172
doi: 10.1016/j.therap.2023.10.008
[2]   HERRMANN J Adverse cardiac effects of cancer therapies: cardiotoxicity and arrhythmia[J]. Nature Reviews Cardiology, 2020, 17 (8): 474- 502
doi: 10.1038/s41569-020-0348-1
[3]   PANG L, SAGER P, YANG X, et al Workshop report FDA workshop on improving cardiotoxicity assessment with human-relevant platforms[J]. Circulation Research, 2019, 125 (9): 855- 867
doi: 10.1161/CIRCRESAHA.119.315378
[4]   CARDINALE D, CIPOLLA C M Assessment of cardiotoxicity with cardiac biomarkers in cancer patients[J]. Herz, 2011, 36 (4): 325- 332
doi: 10.1007/s00059-011-3453-4
[5]   SHARMA A, MCKEITHAN W L, SERRANO R, et al Use of human induced pluripotent stem cell-derived cardiomyocytes to assess drug cardiotoxicity[J]. Nature Protocols, 2018, 13 (12): 3018- 3041
doi: 10.1038/s41596-018-0076-8
[6]   YANG X L, PABON L, MURRY C E Engineering adolescence maturation of human pluripotent stem cell-derived cardiomyocytes[J]. Circulation Research, 2014, 114 (3): 511- 523
doi: 10.1161/CIRCRESAHA.114.300558
[7]   ZHAN H Q, XIA L, SHOU G F, et al Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study[J]. Journal of Zhejiang University: Science B, 2014, 15 (3): 225- 242
doi: 10.1631/jzus.B1300156
[8]   HUEBSCH N, CHARREZ B, NEIMAN G, et al Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips[J]. Nature Biomedical Engineering, 2022, 6 (4): 372- 388
doi: 10.1038/s41551-022-00884-4
[9]   HAN B, TREW M L, ZGIERSKI-JOHNSTON C M Cardiac conduction velocity, remodeling and arrhythmogenesis[J]. Cells, 2021, 10 (11): 2923
doi: 10.3390/cells10112923
[10]   GAO J, LIAO C Y, LIU S J, et al Nanotechnology: new opportunities for the development of patch-clamps[J]. Journal of Nanobiotechnology, 2021, 19 (1): 97
doi: 10.1186/s12951-021-00841-4
[11]   ST-PIERRE F, MARSHALL J D, YANG Y, et al High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor[J]. Nature Neuroscience, 2014, 17 (6): 884- 889
doi: 10.1038/nn.3709
[12]   MILLER E W, LIN J Y, FRADY E P, et al Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109 (6): 2114- 2119
[13]   O'SHEA C, WINTER J, KABIR S N, et al High resolution optical mapping of cardiac electrophysiology in pre-clinical models[J]. Scientific Data, 2022, 9 (1): 135
doi: 10.1038/s41597-022-01253-1
[14]   HELLWEG L, EDENHOFER A, BARCK L, et al A general method for the development of multicolor biosensors with large dynamic ranges[J]. Nature Chemical Biology, 2023, 19 (9): 1147- 1157
doi: 10.1038/s41589-023-01350-1
[15]   JOSHI J, RUBART M, ZHU W Q Optogenetics: background, methodological advances and potential applications for cardiovascular research and medicine[J]. Frontiers in Bioengineering and Biotechnology, 2020, 7: 466
doi: 10.3389/fbioe.2019.00466
[16]   KIM C K, ADHIKARI A, DEISSEROTH K Integration of optogenetics with complementary methodologies in systems neuroscience[J]. Nature Reviews Neuroscience, 2017, 18 (4): 222- 235
doi: 10.1038/nrn.2017.15
[17]   TRANTIDOU T, TERRACCIANO C M, KONTZIAMPASIS D, et al Biorealistic cardiac cell culture platforms with integrated monitoring of extracellular action potentials[J]. Scientific Reports, 2015, 5 (1): 11067
doi: 10.1038/srep11067
[18]   GUZMAN E, CHENG Z W, HANSMA P K, et al Extracellular detection of neuronal coupling[J]. Scientific Reports, 2021, 11 (1): 14733
doi: 10.1038/s41598-021-94282-6
[19]   XU L Q, HU C X, HUANG Q, et al Trends and recent development of the microelectrode arrays (MEAs)[J]. Biosensors and Bioelectronics, 2021, 175: 112854
doi: 10.1016/j.bios.2020.112854
[20]   KARUMBAIAH L, NORMAN S E, RAJAN N B, et al The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion[J]. Biomaterials, 2012, 33 (26): 5983- 5996
doi: 10.1016/j.biomaterials.2012.05.021
[21]   RIBEIRO A J S, ANG Y S, FU J D, et al Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness[J]. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112 (41): 12705- 12710
[22]   BOZKURT A, LAL A Low-cost flexible printed circuit technology based microelectrode array for extracellular stimulation of the invertebrate locomotory system[J]. Sensors and Actuators A: Physical, 2011, 169 (1): 89- 97
doi: 10.1016/j.sna.2011.05.015
[23]   CHOI J S, LEE H J, RAJARAMAN S, et al Recent advances in three-dimensional microelectrode array technologies for in vitro and in vivo cardiac and neuronal interfaces[J]. Biosensors and Bioelectronics, 2021, 171: 112687
doi: 10.1016/j.bios.2020.112687
[24]   BOEHLER C, CARLI S, FADIGA L, et al Tutorial: guidelines for standardized performance tests for electrodes intended for neural interfaces and bioelectronics[J]. Nature Protocols, 2020, 15 (11): 3557- 3578
doi: 10.1038/s41596-020-0389-2
[25]   LIN B, LIN X M, STACHEL M, et al Culture in glucose-depleted medium supplemented with fatty acid and 3, 3′, 5-Triiodo-L-Thyronine facilitates purification and maturation of human pluripotent stem cell-derived cardiomyocytes[J]. Frontiers in Endocrinology, 2017, 8: 253
doi: 10.3389/fendo.2017.00253
[26]   ZHU H Q, SCHARNHORST K S, STIEG A Z, et al Two dimensional electrophysiological characterization of human pluripotent stem cell-derived cardiomyocyte system[J]. Scientific Reports, 2017, 7 (1): 43210
doi: 10.1038/srep43210
[27]   SIRENKO O, CRITTENDEN C, CALLAMARAS N, et al Multiparameter in vitro assessment of compound effects on cardiomyocyte physiology using iPSC cells[J]. Journal of Biomolecular Screening, 2013, 18 (1): 39- 53
doi: 10.1177/1087057112457590
[28]   KITAGUCHI T, MORIYAMA Y, TANIGUCHI T, et al CSAHi study: detection of drug-induced ion channel/receptor responses, QT prolongation, and arrhythmia using multi-electrode arrays in combination with human induced pluripotent stem cell-derived cardiomyocytes[J]. Journal of Pharmacological and Toxicological Methods, 2017, 85: 73- 81
doi: 10.1016/j.vascn.2017.02.001
[29]   CLEMENTS M, THOMAS N High-throughput multi-parameter profiling of electrophysiological drug effects in human embryonic stem cell derived cardiomyocytes using multi-electrode arrays[J]. Toxicological Sciences, 2014, 140 (2): 445- 461
doi: 10.1093/toxsci/kfu084
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