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Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
Microsystems & Nanoengineering ( IF 7.3 ) Pub Date : 2021-03-25 , DOI: 10.1038/s41378-021-00247-0
Jiaru Fang 1 , Xinwei Wei 2 , Hongbo Li 1 , Ning Hu 1, 3 , Xingxing Liu 1 , Dongxin Xu 1 , Tao Zhang 4 , Hao Wan 2, 3 , Ping Wang 2, 3 , Xi Xie 1
Affiliation  

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.



中文翻译:

用于高内涵、剂量定量和时间依赖性药物评估的心肌细胞电-机械同步模型

心血管疾病已成为对人类健康的重大威胁。然而,药物开发是一个耗时且成本高昂的过程,很少有药物能够通过安全性和有效性的临床前评估。现有的用于药物临床前筛选的心肌细胞模型中的膜片钳、Ca 2+成像和微电极阵列技术存在通量低、长期评估有限或无法同步关联分析电信号和机械信号的问题。在这里,我们开发了一个基于机电同步(EMS)生物传感系统的高内涵、剂量定量和时间依赖性药物评估平台。这种微制造的 EMS 可以记录心肌细胞的激发电位 (FP) 和机械搏动 (MB) 信号,并从这两个信号 (FP-MB) 中提取各种特征参数以进行进一步分析。该系统用于测试典型离子通道药物(利多卡因和伊拉地平),并记录和分析心肌细胞对测试药物的动态反应。系统的高通量特性可以方便对大量样品进行同时实验。此外,还可以通过热图分析建立各种心脏药物的数据库,以便快速有效地筛选药物。EMS生物传感系统作为新药临床前开发的有力工具,前景广阔。

更新日期:2021-03-25
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