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微电极阵列在药物发现和基础研究中的生物学应用。

Biological application of microelectrode arrays in drug discovery and basic research.

作者信息

Stett Alfred, Egert Ulrich, Guenther Elke, Hofmann Frank, Meyer Thomas, Nisch Wilfried, Haemmerle Hugo

机构信息

NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Markwiesenstr. 55, 72770, Reutlingen, Germany.

出版信息

Anal Bioanal Chem. 2003 Oct;377(3):486-95. doi: 10.1007/s00216-003-2149-x. Epub 2003 Aug 16.

DOI:10.1007/s00216-003-2149-x
PMID:12923608
Abstract

Electrical activity of electrogenic cells in neuronal and cardiac tissue can be recorded by means of microelectrode arrays (MEAs) that offer the unique possibility for non-invasive extracellular recording from as many as 60 sites simultaneously. Since its introduction 30 years ago, the technology and the related culture methods for electrophysiological cell and tissue assays have been continually improved and have found their way into many academic and industrial laboratories. Currently, this technology is attracting increased interest owing to the industrial need to screen selected compounds against ion channel targets in their native environment at organic, cellular, and sub-cellular level. As the MEA technology can be applied to any electrogenic tissue (i.e., central and peripheral neurons, heart cells, and muscle cells), the MEA biosensor is an ideal in vitro system to monitor both acute and chronic effects of drugs and toxins and to perform functional studies under physiological or induced pathophysiological conditions that mimic in vivo damages. By recording the electrical response of various locations on a tissue, a spatial map of drug effects at different sites can be generated, providing important clues about a drug's specificity. In this survey, examples of MEA biosensor applications are described that have been developed for drug screening and discovery and safety pharmacology in the field of cardiac and neural research. Additionally, biophysical basics of recording and concepts for analysis of extracellular electrical signals are presented.

摘要

神经元和心脏组织中电生细胞的电活动可以通过微电极阵列(MEA)进行记录,微电极阵列提供了同时从多达60个位点进行非侵入性细胞外记录的独特可能性。自30年前引入以来,用于电生理细胞和组织检测的技术及相关培养方法不断改进,并已进入许多学术和工业实验室。目前,由于在有机、细胞和亚细胞水平的天然环境中筛选针对离子通道靶点的特定化合物的工业需求,这项技术正吸引着越来越多的关注。由于MEA技术可应用于任何电生组织(即中枢和外周神经元、心脏细胞和肌肉细胞),MEA生物传感器是一种理想的体外系统,可监测药物和毒素的急性和慢性效应,并在模拟体内损伤的生理或诱导病理生理条件下进行功能研究。通过记录组织上不同位置的电反应,可以生成药物在不同位点作用的空间图谱,为药物的特异性提供重要线索。在本次综述中,描述了MEA生物传感器在心脏和神经研究领域用于药物筛选与发现以及安全药理学方面的应用实例。此外,还介绍了记录的生物物理基础以及细胞外电信号分析的概念。

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