Dou Wenkun, Malhi Manpreet, Cui Teng, Wang Minyao, Wang Tiancong, Shan Guanqiao, Law Junhui, Gong Zheyuan, Plakhotnik Julia, Filleter Tobin, Li Renke, Simmons Craig A, Maynes Jason T, Sun Yu
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario M5S 3G8, Canada.
Program in Molecular Medicine, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
ACS Nano. 2022 Jul 26;16(7):11278-11290. doi: 10.1021/acsnano.2c04676. Epub 2022 Jun 17.
Heart beating is triggered by the generation and propagation of action potentials through the myocardium, resulting in the synchronous contraction of cardiomyocytes. This process highlights the importance of electrical and mechanical coordination in organ function. Investigating the pathogenesis of heart diseases and potential therapeutic actions requires biosensing technologies which allow for long-term and simultaneous measurement of the contractility and electrophysiology of cardiomyocytes. However, the adoption of current biosensing approaches for functional measurement of cardiac models is hampered by low sensitivity, difficulties in achieving multifunctional detection, and costly manufacturing processes. Leveraging carbon-based nanomaterials, we developed a biosensing platform that is capable of performing on-chip and simultaneous measurement of contractility and electrophysiology of human induced pluripotent stem-cell-derived cardiomyocyte (iPSC-CM) monolayers. This platform integrates with a flexible thin-film cantilever embedded with a carbon black (CB)-PDMS strain sensor for high-sensitivity contraction measurement and four pure carbon nanotube (CNT) electrodes for the detection of extracellular field potentials with low electrode impedance. Cardiac functional properties including contractile stress, beating rate, beating rhythm, and extracellular field potential were evaluated to quantify iPSC-CM responses to common cardiotropic agents. In addition, an model of drug-induced cardiac arrhythmia was established to further validate the platform for disease modeling and drug testing.
心脏跳动是由动作电位在心肌中的产生和传播所触发的,从而导致心肌细胞的同步收缩。这一过程突出了器官功能中电和机械协调的重要性。研究心脏病的发病机制和潜在治疗作用需要生物传感技术,该技术能够长期同时测量心肌细胞的收缩性和电生理学。然而,目前用于心脏模型功能测量的生物传感方法存在灵敏度低、难以实现多功能检测以及制造过程成本高昂等问题。利用碳基纳米材料,我们开发了一种生物传感平台,该平台能够在芯片上同时测量人诱导多能干细胞衍生心肌细胞(iPSC-CM)单层的收缩性和电生理学。该平台与一个柔性薄膜悬臂集成,该悬臂嵌入了用于高灵敏度收缩测量的炭黑(CB)-聚二甲基硅氧烷应变传感器和用于检测低电极阻抗细胞外场电位的四个纯碳纳米管(CNT)电极。评估了包括收缩应力、跳动频率、跳动节律和细胞外场电位在内的心脏功能特性,以量化iPSC-CM对常见强心剂的反应。此外,还建立了药物诱导心律失常模型,以进一步验证该平台用于疾病建模和药物测试的能力。