Yuan Qunchen, Qin Chunlian, Xu Dongxin, Qiu Yong, Hu Jiahao, Wan Hao, Hu Ning, Wang Ping
Biosensor National Special Laboratory, Key Laboratory for Biomedical Engineering of Education Ministry, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.
Innovation Center for Smart Medical Technologies & Devices, Binjiang Institute of Zhejiang University, Hangzhou, Zhejiang 310053, China.
ACS Sens. 2025 Jan 24;10(1):460-469. doi: 10.1021/acssensors.4c02755. Epub 2024 Dec 26.
Three-dimensional (3D) cardiomyocyte spheroids are essential models to replicate cardiac structural and functional features in vitro. However, conventional planar and rigid microelectrode arrays (MEAs) suffer from low-quality electrophysiological recording of 3D cultures, due to limited contact areas and weak coupling between cells and MEA chips. Herein, we developed a PEDOT: PSS-modified organic flexible and implantable MEA (OFI-MEA) coupled with a self-developed integrated biosensing platform to achieve high-throughput, long-term, and stable bidirectional internal electrophysiology in 3D cardiomyocyte spheroids. Electrostimulation enhanced the functional performance of the 3D cardiomyocytes, causing a remarkable 2.69-fold increase in frequency. Furthermore, time-frequency analysis of the multisite electrophysiological signals to highlight diverse cell activity patterns in the spheroids. It provides a powerful tool to record electrophysiological signals of 3D cardiomyocyte spheroids, allowing continuing evaluation of cardiac dynamics and regulation of electrical signals, providing a novel evaluation strategy for cardiac disease model construction, drug screening, and cardiological research.
三维（3D）心肌细胞球体是在体外复制心脏结构和功能特征的重要模型。然而，传统的平面刚性微电极阵列（MEA）由于接触面积有限以及细胞与MEA芯片之间的耦合较弱，在对3D培养物进行电生理记录时质量较低。在此，我们开发了一种聚（3,4-乙撑二氧噻吩）：聚苯乙烯磺酸盐（PEDOT：PSS）修饰的有机柔性可植入MEA（OFI-MEA），并结合自主研发的集成生物传感平台，以实现对3D心肌细胞球体的高通量、长期和稳定的双向内部电生理研究。电刺激增强了3D心肌细胞的功能性能，使频率显著增加了2.69倍。此外，通过对多部位电生理信号进行时频分析，突出了球体中不同的细胞活动模式。它为记录3D心肌细胞球体的电生理信号提供了一个强大的工具，能够持续评估心脏动力学和电信号调节，为心脏病模型构建、药物筛选和心脏病学研究提供了一种新的评估策略。
