Dou Wenkun, Daoud Abdelkader, Chen Xin, Wang Tiancong, Malhi Manpreet, Gong Zheyuan, Mirshafiei Fatemeh, Zhu Min, Shan Guanqiao, Huang Xi, 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.
Nano Lett. 2023 Mar 22;23(6):2321-2331. doi: 10.1021/acs.nanolett.3c00017. Epub 2023 Mar 9.
Emerging heart-on-a-chip technology is a promising tool to establish cardiac models for therapeutic testing and disease modeling. However, due to the technical complexity of integrating cell culture chambers, biosensors, and bioreactors into a single entity, a microphysiological system capable of reproducing controlled microenvironmental cues to regulate cell phenotypes, promote iPS-cardiomyocyte maturity, and simultaneously measure the dynamic changes of cardiomyocyte function is not available. This paper reports an ultrathin and flexible bioelectronic array platform in 24-well format for higher-throughput contractility measurement under candidate drug administration or defined microenvironmental conditions. In the array, carbon black (CB)-PDMS flexible strain sensors were embedded for detecting iPSC-CM contractility signals. Carbon fiber electrodes and pneumatic air channels were integrated to provide electrical and mechanical stimulation to improve iPSC-CM maturation. Performed experiments validate that the bioelectronic array accurately reveals the effects of cardiotropic drugs and identifies mechanical/electrical stimulation strategies for promoting iPSC-CM maturation.
新兴的芯片上心脏技术是一种很有前景的工具，可用于建立用于治疗测试和疾病建模的心脏模型。然而，由于将细胞培养室、生物传感器和生物反应器集成到一个单一实体中的技术复杂性，目前还没有一种能够再现可控微环境线索以调节细胞表型、促进诱导多能干细胞衍生心肌细胞（iPS-CM）成熟并同时测量心肌细胞功能动态变化的微生理系统。本文报道了一种24孔格式的超薄柔性生物电子阵列平台，用于在候选药物给药或特定微环境条件下进行更高通量的收缩性测量。在该阵列中，嵌入了炭黑（CB）-聚二甲基硅氧烷（PDMS）柔性应变传感器，用于检测iPSC-CM的收缩性信号。集成了碳纤维电极和气动空气通道，以提供电刺激和机械刺激，从而促进iPSC-CM的成熟。所进行的实验验证了该生物电子阵列能够准确揭示强心药物的作用，并确定促进iPSC-CM成熟的机械/电刺激策略。
