Fang Jiaru, Wei Xinwei, Li Hongbo, Hu Ning, Liu Xingxing, Xu Dongxin, Zhang Tao, Wan Hao, Wang Ping, Xie Xi
The 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 University, Guangzhou, 510006 China.
Biosensor National Special Laboratory, Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou, 310027 China.
Microsyst Nanoeng. 2021 Mar 25;7:26. doi: 10.1038/s41378-021-00247-0. eCollection 2021.
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, Ca 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.
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，很少有药物能通过临床前的安全性和有效性评估。现有的用于药物临床前筛选的心肌细胞模型中的膜片钳、钙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和相关分析电信号和机械信号等问题。在此，我们基于机电同步（EMS）生物传感系统开发了一个高内涵、剂量定量且随时间变化的药物评估平台。这种微制造的EMS可以记录心肌细胞的动作电位（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。该系统应用于测试典型的离子通道药物（利多卡因和伊拉地平），并记录和分析了心肌细胞对受试药物的动态反应。该系统的高通量特性有助于对大量样品同时进行实验。此外，通过热图分析可以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具有很大的前景。
