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使用基于高速阻抗检测技术的芯片心脏进行药物心脏安全性的高通量评估。

High-Throughput Assessment of Drug Cardiac Safety Using a High-Speed Impedance Detection Technology-Based Heart-on-a-Chip.

作者信息

Zhang Xi, Wang Tianxing, Wang Ping, Hu Ning

机构信息

Key Laboratory of Biomedical Engineering of Ministry of Education, Biosensor National Special Laboratory, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.

ACEA Biosciences (Hangzhou) Co., Ltd., High Throughput Drug Screening Center, Xihu Technology and Economy Park, Hangzhou 310030, China.

出版信息

Micromachines (Basel). 2016 Jul 19;7(7):122. doi: 10.3390/mi7070122.

Abstract

Drug cardiac safety assessments play a significant role in drug discovery. Drug-induced cardiotoxicity is one of the main reasons for drug attrition, even when antiarrhythmic drugs can otherwise effectively treat the arrhythmias. Consequently, efficient drug preclinical assessments are needed in the drug industry. However, most drug efficacy assessments are performed based on electrophysiological tests of cardiomyocytes in vitro and cannot effectively provide information on drug-induced dysfunction of cardiomyocyte beating. Here we present a heart-on-a-chip device for evaluating the drug cardiac efficacy using a high-speed impedance detection technology. Verapamil and doxorubicin were utilized to test this heart-on-a-chip, and multiple parameters of cardiomyocyte beating status are used to reveal the effects of drugs. The results show that drug efficacy or cardiotoxicity can be determined by this heart-on-a-chip. We believe this heart-on-a-chip will be a promising tool for the preclinical assessment of drug cardiac efficacy.

摘要

药物心脏安全性评估在药物研发中发挥着重要作用。药物性心脏毒性是药物研发失败的主要原因之一,即使抗心律失常药物在其他方面能够有效治疗心律失常。因此,制药行业需要高效的临床前药物评估。然而,大多数药物疗效评估是基于体外心肌细胞的电生理测试进行的,无法有效提供药物诱导的心肌细胞搏动功能障碍的信息。在此,我们展示了一种使用高速阻抗检测技术评估药物心脏疗效的芯片心脏装置。使用维拉帕米和阿霉素对该芯片心脏进行测试,并利用心肌细胞搏动状态的多个参数来揭示药物的作用。结果表明,该芯片心脏能够确定药物疗效或心脏毒性。我们相信,这种芯片心脏将成为药物心脏疗效临床前评估的一种有前景的工具。

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