Impedimetric Monitoring of Cell‐Based Assays

Abstract

Abstract Electrochemical impedance measurements (electric cell‐substrate impedance sensing, ECIS) have been established as a label‐free and noninvasive experimental tool to monitor and quantify the behaviour of adherent cells grown on planar gold‐film electrodes while they are exposed to chemical, biological or physical stimuli/stressors. Owing to the noninvasiveness of the measurement, impedance‐based cell observation provides continuous information about the cell response in real time. Different data acquisition modes in combination with tailored electrode layouts are used to assess the time courses of several fundamental processes in cell physiology such as cell adhesion, cell proliferation, cell migration, intracellular signal transduction or cell death. Experiments are performed entirely automated and computer‐controlled under regular cell culture conditions. State‐of‐the‐art instrumentation allows for the parallel analysis of up to 384 samples. Its multimodality and throughput suggest that ECIS can play a similar role for the analysis of cell‐based assays as flow cytometry. Key Concepts Electric cell‐substrate impedance sensing (ECIS) is a noninvasive experimental technique to monitor adherent cells in vitro along different types of biomedical or bioanalytical assays with a time resolution that is adjustable from milliseconds to hours. To perform ECIS‐based assays, the cells are grown on planar gold‐film electrodes deposited on the surface of a regular cell culture dish. ECIS is compatible with regular cell culture conditions, fully automated and software controlled. The approach is sensitive to (1) the fractional coverage of the electrode surface and (2) the three‐dimensional shape of the cells attached to the electrode. ECIS is significantly more sensitive for cell shape changes than optical microscopy. On the basis of this generic sensitivity, different assays have been developed to monitor cell adhesion to biomaterial surfaces, cell proliferation, cell migration, cell death or the stimulation of cell‐surface receptors. The scope of available assay formats has been further extended using elevated electric fields for well‐defined cell manipulation integrated into continuous, impedance‐based cell monitoring (e.g. in situ electroporation).