Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential

Abstract Microelectrode arrays (MEAs) are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format. However, they typically lack the capability to record intracellular action potentials (APs). Recent studies have relied on costly fabrication of hig...

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Main Authors: Xingyuan Xu, Zhengjie Liu, Jing Liu, Chuanjie Yao, Xi Chen, Xinshuo Huang, Shuang Huang, Peng Shi, Mingqiang Li, Li Wang, Yu Tao, Hui-jiuan Chen, Xi Xie
Format: Article
Language:English
Published: Nature Publishing Group 2025-05-01
Series:Microsystems & Nanoengineering
Online Access:https://doi.org/10.1038/s41378-025-00887-6
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author Xingyuan Xu
Zhengjie Liu
Jing Liu
Chuanjie Yao
Xi Chen
Xinshuo Huang
Shuang Huang
Peng Shi
Mingqiang Li
Li Wang
Yu Tao
Hui-jiuan Chen
Xi Xie
author_facet Xingyuan Xu
Zhengjie Liu
Jing Liu
Chuanjie Yao
Xi Chen
Xinshuo Huang
Shuang Huang
Peng Shi
Mingqiang Li
Li Wang
Yu Tao
Hui-jiuan Chen
Xi Xie
author_sort Xingyuan Xu
collection DOAJ
description Abstract Microelectrode arrays (MEAs) are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format. However, they typically lack the capability to record intracellular action potentials (APs). Recent studies have relied on costly fabrication of high-resolution microelectrodes combined with electroporation for intracellular recordings, but the impact of microelectrode size on micro-electroporation and the quality of intracellular signal acquisition has yet to be explored. Understanding these effects could facilitate the design of microelectrodes of various sizes to enable lower-cost manufacturing processes. In this study, we investigated the influence of microelectrode size on intracellular AP parameters and recording metrics post-micro-electroporation through simulations and experiments. We fabricated microelectrodes of different sizes using standard photolithography techniques to record cardiomyocyte APs from various culture environments with coupled micro-electroporation. Our findings indicate that larger microelectrodes generally recorded electrophysiological signals with higher amplitude and better signal-to-noise ratios, while smaller electrodes exhibited higher perforation efficiency, AP duration, and single-cell signal ratios. This work demonstrates that the micro-electroporation technique can be applied to larger microelectrodes for intracellular recordings, rather than being limited to high-resolution designs. This approach may provide new opportunities for fabricating microelectrodes using alternative low-cost manufacturing techniques for high-quality intracellular AP recordings.
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spelling doaj-art-1cf4e993fdac42c99c68d2d5613d53d62025-08-20T03:48:02ZengNature Publishing GroupMicrosystems & Nanoengineering2055-74342025-05-0111111810.1038/s41378-025-00887-6Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potentialXingyuan Xu0Zhengjie Liu1Jing Liu2Chuanjie Yao3Xi Chen4Xinshuo Huang5Shuang Huang6Peng Shi7Mingqiang Li8Li Wang9Yu Tao10Hui-jiuan Chen11Xi Xie12State Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityState Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityThe First Affiliated Hospital of Sun Yat-Sen UniversityState Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityShanghai Namin Core Technology Co.State Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityState Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityDepartment of Biomedical Engineering, City University of Hong KongLaboratory of Biomaterials and Translational Medicine, Centre for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen UniversitySchool of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences)Laboratory of Biomaterials and Translational Medicine, Centre for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen UniversityState Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityState Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-Sen UniversityAbstract Microelectrode arrays (MEAs) are essential tools for studying the extracellular electrophysiology of cardiomyocytes in a multi-channel format. However, they typically lack the capability to record intracellular action potentials (APs). Recent studies have relied on costly fabrication of high-resolution microelectrodes combined with electroporation for intracellular recordings, but the impact of microelectrode size on micro-electroporation and the quality of intracellular signal acquisition has yet to be explored. Understanding these effects could facilitate the design of microelectrodes of various sizes to enable lower-cost manufacturing processes. In this study, we investigated the influence of microelectrode size on intracellular AP parameters and recording metrics post-micro-electroporation through simulations and experiments. We fabricated microelectrodes of different sizes using standard photolithography techniques to record cardiomyocyte APs from various culture environments with coupled micro-electroporation. Our findings indicate that larger microelectrodes generally recorded electrophysiological signals with higher amplitude and better signal-to-noise ratios, while smaller electrodes exhibited higher perforation efficiency, AP duration, and single-cell signal ratios. This work demonstrates that the micro-electroporation technique can be applied to larger microelectrodes for intracellular recordings, rather than being limited to high-resolution designs. This approach may provide new opportunities for fabricating microelectrodes using alternative low-cost manufacturing techniques for high-quality intracellular AP recordings.https://doi.org/10.1038/s41378-025-00887-6
spellingShingle Xingyuan Xu
Zhengjie Liu
Jing Liu
Chuanjie Yao
Xi Chen
Xinshuo Huang
Shuang Huang
Peng Shi
Mingqiang Li
Li Wang
Yu Tao
Hui-jiuan Chen
Xi Xie
Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential
Microsystems & Nanoengineering
title Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential
title_full Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential
title_fullStr Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential
title_full_unstemmed Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential
title_short Multi-sized microelectrode array coupled with micro-electroporation for effective recording of intracellular action potential
title_sort multi sized microelectrode array coupled with micro electroporation for effective recording of intracellular action potential
url https://doi.org/10.1038/s41378-025-00887-6
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