Research Center for Intelligent Sensing Systems, Zhejiang Laboratory, Hangzhou, 311100, China.
Department of Obstetrics and Gynecology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan, 523059, China.
Biosens Bioelectron. 2022 Sep 15;212:114387. doi: 10.1016/j.bios.2022.114387. Epub 2022 May 20.
The development of new drugs is a lengthy process, while the observation of serious side effects, such as cardiotoxicity, can result in the drug to be withdrawn even after development, leading to heavy burden on human health and social economy. To assess the drug cardiotoxicity, the electrical and mechanical properties of cardiomyocytes are increasingly being used to investigate the mechanisms and potential toxicity of drugs. Conventional non-invasive and label-free recording strategies are not well suited to record the integrated electromechanical signals from the single cell in a high-throughput manner, whereas label-based recordings strategies suffer from phototoxicity and drug side effects, precluding their long-time detection. In this study, we established a new multimodal microelectrode biosensing system to achieve the simultaneous and dynamic interrogation of electromechanical signals from multisite single cardiomyocytes. This multimodal device can detect subtle changes in the electromechanical signals induced by ion channel drugs during the excitation-contraction coupling of cardiomyocytes. The use of electromechanical integrated single cell signals for drug assessment was compared with commercial drug assays, and our multimodal microelectrode biosensing system can afford record electromechanical integrated signals as well as efficiently identify the effects of ion channel-blocking drugs on the electrical and mechanical properties of cardiomyocytes. Our multimodal microelectrode biosensing system is a potential valuable platform in the fields of cardiology and pharmacology.
新药的研发是一个漫长的过程，而严重副作用（如心脏毒性）的观察可能导致药物在研发后被撤回，从而给人类健康和社会经济带来沉重负担。为了评估药物的心脏毒性，可以使用心肌细胞的电和机械特性来研究药物的机制和潜在毒性。传统的非侵入性和无标记记录策略不太适合高通量地记录单个细胞的整合机电信号，而基于标记的记录策略则存在光毒性和药物副作用的问题，无法进行长时间的检测。在本研究中，我们建立了一种新的多模态微电极生物传感系统，以实现多部位单细胞机电信号的同时和动态询问。该多模态装置可检测离子通道药物在心肌细胞兴奋-收缩偶联过程中引起的机电信号的细微变化。将机电整合的单细胞信号用于药物评估与商业药物检测进行了比较，我们的多模态微电极生物传感系统可以记录机电整合信号，并有效地识别离子通道阻断药物对心肌细胞电和机械特性的影响。我们的多模态微电极生物传感系统是心脏病学和药理学领域有前途的有价值平台。
