Biological application of microelectrode arrays in drug discovery and basic research.
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.
Stett
Alfred
A
NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Markwiesenstr. 55, 72770, Reutlingen, Germany.
Egert
Ulrich
U
Guenther
Elke
E
Hofmann
Frank
F
Meyer
Thomas
T
Nisch
Wilfried
W
Haemmerle
Hugo
H
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects; D006801:Humans; D008839:Microelectrodes; D009206:Myocardium / Q000166:cytology; D009474:Neurons / Q000502:physiology; D009924:Organ Culture Techniques