Dou Wenkun, Malhi Manpreet, Zhao Qili, Wang Li, Huang Zongjie, Law Junhui, Liu Na, Simmons Craig A, Maynes Jason T, Sun Yu
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8 Canada.
Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8 Canada.
Microsyst Nanoeng. 2022 Feb 28;8:26. doi: 10.1038/s41378-021-00344-0. eCollection 2022.
Emerging heart-on-a-chip platforms are promising approaches to establish cardiac cell/tissue models in vitro for research on cardiac physiology, disease modeling and drug cardiotoxicity as well as for therapeutic discovery. Challenges still exist in obtaining the complete capability of in situ sensing to fully evaluate the complex functional properties of cardiac cell/tissue models. Changes to contractile strength (contractility) and beating regularity (rhythm) are particularly important to generate accurate, predictive models. Developing new platforms and technologies to assess the contractile functions of in vitro cardiac models is essential to provide information on cell/tissue physiologies, drug-induced inotropic responses, and the mechanisms of cardiac diseases. In this review, we discuss recent advances in biosensing platforms for the measurement of contractile functions of in vitro cardiac models, including single cardiomyocytes, 2D monolayers of cardiomyocytes, and 3D cardiac tissues. The characteristics and performance of current platforms are reviewed in terms of sensing principles, measured parameters, performance, cell sources, cell/tissue model configurations, advantages, and limitations. In addition, we highlight applications of these platforms and relevant discoveries in fundamental investigations, drug testing, and disease modeling. Furthermore, challenges and future outlooks of heart-on-a-chip platforms for in vitro measurement of cardiac functional properties are discussed.
新兴的芯片上心脏平台是在体外建立心脏细胞/组织模型的有前景的方法,可用于心脏生理学研究、疾病建模、药物心脏毒性研究以及治疗发现。在获得完整的原位传感能力以全面评估心脏细胞/组织模型的复杂功能特性方面,仍然存在挑战。收缩强度(收缩性)和搏动规律性(节律)的变化对于生成准确的预测模型尤为重要。开发新的平台和技术来评估体外心脏模型的收缩功能对于提供有关细胞/组织生理学、药物诱导的变力反应以及心脏疾病机制的信息至关重要。在这篇综述中,我们讨论了用于测量体外心脏模型收缩功能的生物传感平台的最新进展,包括单个心肌细胞、心肌细胞的二维单层和三维心脏组织。从传感原理、测量参数、性能、细胞来源、细胞/组织模型配置、优点和局限性等方面对当前平台的特点和性能进行了综述。此外,我们强调了这些平台在基础研究、药物测试和疾病建模中的应用以及相关发现。此外,还讨论了用于体外测量心脏功能特性的芯片上心脏平台的挑战和未来展望。