Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
Abstract Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca2+ imaging, and microelectrode array technologies...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-03-01
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| Series: | Microsystems & Nanoengineering |
| Online Access: | https://doi.org/10.1038/s41378-021-00247-0 |
| _version_ | 1818454150907691008 |
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| author | Jiaru Fang Xinwei Wei Hongbo Li Ning Hu Xingxing Liu Dongxin Xu Tao Zhang Hao Wan Ping Wang Xi Xie |
| author_facet | Jiaru Fang Xinwei Wei Hongbo Li Ning Hu Xingxing Liu Dongxin Xu Tao Zhang Hao Wan Ping Wang Xi Xie |
| author_sort | Jiaru Fang |
| collection | DOAJ |
| description | Abstract Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca2+ imaging, and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput, limited long-term assessment, or inability to synchronously and correlatively analyze electrical and mechanical signals. Here, we develop a high-content, dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized (EMS) biosensing system. This microfabricated EMS can record both firing potential (FP) and mechanical beating (MB) signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals (FP–MB) for further analysis. This system was applied to test typical ion channel drugs (lidocaine and isradipine), and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed. The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples. Furthermore, a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs. The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines. |
| first_indexed | 2024-12-14T21:50:19Z |
| format | Article |
| id | doaj.art-6e176150c0fb4195824557c98a5a73c8 |
| institution | Directory Open Access Journal |
| issn | 2055-7434 |
| language | English |
| last_indexed | 2024-12-14T21:50:19Z |
| publishDate | 2021-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Microsystems & Nanoengineering |
| spelling | doaj.art-6e176150c0fb4195824557c98a5a73c82022-12-21T22:46:16ZengNature Publishing GroupMicrosystems & Nanoengineering2055-74342021-03-017111210.1038/s41378-021-00247-0Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessmentJiaru Fang0Xinwei Wei1Hongbo Li2Ning Hu3Xingxing Liu4Dongxin Xu5Tao Zhang6Hao Wan7Ping Wang8Xi Xie9The First Affiliated Hospital of Sun Yat-Sen University; School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-sen UniversityBiosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang UniversityThe First Affiliated Hospital of Sun Yat-Sen University; School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-sen UniversityThe First Affiliated Hospital of Sun Yat-Sen University; School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-sen UniversityThe First Affiliated Hospital of Sun Yat-Sen University; School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-sen UniversityThe First Affiliated Hospital of Sun Yat-Sen University; School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-sen UniversitySchool of Biomedical Engineering, Sun Yat-sen UniversityBiosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang UniversityBiosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang UniversityThe First Affiliated Hospital of Sun Yat-Sen University; School of Electronics and Information Technology, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-sen UniversityAbstract Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca2+ imaging, and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput, limited long-term assessment, or inability to synchronously and correlatively analyze electrical and mechanical signals. Here, we develop a high-content, dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized (EMS) biosensing system. This microfabricated EMS can record both firing potential (FP) and mechanical beating (MB) signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals (FP–MB) for further analysis. This system was applied to test typical ion channel drugs (lidocaine and isradipine), and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed. The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples. Furthermore, a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs. The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.https://doi.org/10.1038/s41378-021-00247-0 |
| spellingShingle | Jiaru Fang Xinwei Wei Hongbo Li Ning Hu Xingxing Liu Dongxin Xu Tao Zhang Hao Wan Ping Wang Xi Xie Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment Microsystems & Nanoengineering |
| title | Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment |
| title_full | Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment |
| title_fullStr | Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment |
| title_full_unstemmed | Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment |
| title_short | Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment |
| title_sort | cardiomyocyte electrical mechanical synchronized model for high content dose quantitative and time dependent drug assessment |
| url | https://doi.org/10.1038/s41378-021-00247-0 |
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