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基于优化机械搏动检测的单细胞心肌的通用且灵敏的药物评估生物传感平台。

Universal and Sensitive Drug Assessment Biosensing Platform Using Optimal Mechanical Beating Detection of Single Cardiomyocyte.

机构信息

State Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-sen University, Guangzhou 510006, China.

ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311200, China.

出版信息

ACS Nano. 2022 Sep 27;16(9):15484-15494. doi: 10.1021/acsnano.2c08049. Epub 2022 Sep 12.

Abstract

The preclinical assessment of efficacy and safety is essential for cardiovascular drug development in order to guarantee effective prevention and treatment of cardiovascular disease and avoid human health endangerment and a huge waste of resources. Rhythmic mechanical beating as one of the crucial cardiomyocyte properties has been exploited to establish a drug assessment biosensing platform. However, the conventional label-free biosensing platforms are difficult to perform high-throughput and high-resolution mechanical beating detection for a single cardiomyocyte, while label-based strategies are limited by pharmacologically adverse effects and phototoxicity. Herein, we propose a biosensing platform involving the multichannel electrode array device and the universal mechanical beating detection system. The platform can determine the optimal characteristic working frequency of different devices and dynamically interrogate the viability of multisite single cardiomyocytes to establish the optimized cell-based model for sensitive drug assessment. The subtle changes of mechanical beating signals induced by cardiovascular drugs can be detected by the platform, thereby demonstrating its high performance in pharmacological assessment. The universal and sensitive drug assessment biosensing platform is believed to be widely applied in cardiology investigating and preclinical drug screening.

摘要

临床前的疗效和安全性评估对于心血管药物的开发至关重要,这可以保证有效的心血管疾病预防和治疗,避免对人类健康的危害和资源的巨大浪费。节律性机械跳动作为心肌细胞的关键特性之一,已被用于建立药物评估生物传感平台。然而,传统的无标记生物传感平台难以对单个心肌细胞进行高通量和高分辨率的机械跳动检测,而基于标记的策略则受到药理学不良反应和光毒性的限制。在此,我们提出了一种涉及多通道电极阵列装置和通用机械跳动检测系统的生物传感平台。该平台可以确定不同设备的最佳特征工作频率,并动态询问多部位单细胞心肌细胞的活力,从而建立用于敏感药物评估的优化细胞模型。该平台可以检测心血管药物引起的机械跳动信号的细微变化,从而证明其在药理学评估中的优异性能。通用且敏感的药物评估生物传感平台有望在心脏病学研究和临床前药物筛选中得到广泛应用。

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