Impedance-based assays along the life span of adherent mammalian cells in vitro: From initial adhesion to cell death

Impedance-based monitoring of adherent cells has gained increasing acceptance in many areas of biomedical research and drug discovery, as it provides a noninvasive and label-free experimental tool to continuously monitor cell behavior in response to biological, chemical, or physical stimuli. It is based on growing cells on thin-film electrodes that are deposited on the bottom of regular cell cultureware and monitoring the electrical impedance of these electrodes as a function of frequency and time. Tailored hardware, data acquisition modes, electrode designs, and assay procedures have been developed for a fully automated and time-resolved observation of various cell phenotypes and phenotypic changes disclosed in cell-matrix adhesion, proliferation, differentiation, cell migration, signal transduction, or cell death. Impedance-based cell analysis is performed under regular cell culture conditions and applied for short-term and long-term observation of cell behavior. This review will recapitulate the physical principles of the measurement and highlight its applications not without critical assessment of its limitations. The most prominent impedance-based assays will be explained and discussed with reference to an extended literature survey of the field.