项目名称： 基于多功能心肌细胞传感器的机电一体化离体检测及其药物应用的研究

项目编号： No.81501553

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 胡宁

作者单位： 浙江大学

项目金额： 18万元

中文摘要： 药物引起的心脏毒性是导致药物停止发展、限制使用和撤回的主因，因而在药物开发的早期，对药物进行心脏安全性分析有助于降低药物被撤回的可能性。本项目研制一种新型的多功能心肌细胞传感器，建立一种新型心肌细胞机电一体化同步检测的离体药物分析平台。该细胞研究分析平台以细胞传感器技术为基础，结合细胞胞外电位检测技术和细胞阻抗检测技术，实现对心肌细胞电兴奋和收缩的同步检测。在此基础上，构建新型的心肌细胞传感器，从而获取新型的机电一体化参数，建立新型的离体心肌细胞模型。在离体模型建立和测试过程中，采用各种典型的离子通道工具药物，研究药物与新型模型的参数变化的相互联系，从而建立药物的机电一体化特异性模型和评价方法。本项目将为药物心脏分析提供一种无标记、非侵入式、长时、高通量、多参数联合的心肌细胞离体研究平台，成为现有药物心脏安全性分析方法的有效补充和发展。

中文关键词： 微电极阵列；集成化；生物传感系统；药物筛选

英文摘要： Drug-induced cardiotoxicity is the main reason of drug development stop, usage limitation and withdrawal, so in the early stage of drug development, the drug cardiac safety assessment is helpful to reduce the probability of drug withdrawal. In this project, a new in vitro drug analysis platform is established for electromechanical integration simultaneous detection of cardiomyocytes using a new multifunction cardiomyocyte-based biosensor. This cellular study platform is based on the cell-based biosensor technology to realize the excitation and contraction simultaneous detection of cardiomyocytes, employing extracellular potential detection technology and cellular impedance detection technology. Based on these methods, a novel cardiomyocyte-based biosensor and in vitro cardiomyocyte model are constructed with new electromechanical integration parameters. To build and test in vitro model, typical ion-channel drugs are employed to study the relationship between drug and model parameter changes to establish drugs the electromechanical integration specific model and assessment method. This project will provide a label-free, non-invasive, long-term, high-throughput, and multiparameter-combined cardiomyocyte in vitro study platform for drug cardiac safety analysis, and will be an effective complement and development for present available drug cardiac safety analysis methods.

英文关键词： Microelectrode array;Integration;Biosensing system;Drug Screening