Liang Zhixiang, Li Huimin, Han Junlei, Chen Jun, Ding Jiemeng, Tang Wenteng, Wang Minghui, Meng Qi, Zhang Lei, Zhang Zetao, Wang Li
School of Mechanical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
Shandong Institute of Mechanical Design and Research, Jinan 250353, China.
Analyst. 2025 Jul 7;150(14):3188-3197. doi: 10.1039/d5an00315f.
Cardiovascular toxicity is a key safety indicator that has to be evaluated in the process of new drug development. To enable high-throughput and multiparametric assessment of cardiomyocyte function, we developed a 32-well high-throughput microelectrode array (MEA) platform integrated with electrical stimulation. Electrode surface modification with PEDOT:PSS-MWCNT nanocomposites significantly enhanced electrochemical performance and signal acquisition fidelity, reducing electrode impedance by 37-fold compared to unmodified Au electrodes. Notably, the built-in electrical stimulation effectively promoted electrophysiological and structural maturation of human iPSC-cardiomyocytes, demonstrated by a 15.47% increase in sarcomere length and 1.73-fold upregulation of connexin-43 expression. The platform's utility was further validated through cardiotoxicity assessment of two representative ion channel modulators, E-4031 (a selective hERG channel blocker) and verapamil (a clinically used calcium channel blocker). Collectively, this study presents an integrated platform that combines functional monitoring with cellular maturation enhancement, offering a powerful tool for cardiotoxicity screening and disease modeling.
心血管毒性是新药研发过程中必须评估的关键安全指标。为了实现对心肌细胞功能的高通量和多参数评估，我们开发了一种集成电刺激的32孔高通量微电极阵列（MEA）平台。用PEDOT:PSS-MWCNT纳米复合材料对电极表面进行修饰显著提高了电化学性能和信号采集保真度，与未修饰的金电极相比，电极阻抗降低了37倍。值得注意的是，内置的电刺激有效地促进了人诱导多能干细胞衍生心肌细胞（iPSC-心肌细胞）的电生理和结构成熟，肌节长度增加了15.47%，连接蛋白43表达上调了1.73倍。通过对两种代表性离子通道调节剂E-4031（一种选择性hERG通道阻滞剂）和维拉帕米（一种临床使用的钙通道阻滞剂）进行心脏毒性评估，进一步验证了该平台的实用性。总的来说，本研究提出了一个将功能监测与细胞成熟增强相结合的集成平台，为心脏毒性筛选和疾病建模提供了一个强大的工具。
