An Emerging Impedance Sensor Based on Cell-Protein Interactions: Applications in Cell Biology and Analytical Biochemistry

Electric cell-substrate impedance sensing (ECIS) is described for real time monitoring of cell behavior including attachment, motility, and cytotoxicity in a continuous fashion. This emerging technology subjects cells growing on microelectrodes to small ac electric fields. Cells interact differently with various proteins used to precoat the gold electrode. Initial intact extracellular matrix protein binding to cells is often mediated through adhesion receptors in the integrin family with fibronectin as the commonest coating protein. Upon the attachment and spreading of cells, the impedance increases because the cells act as insulating particles to restrict the current flow. An intriguing feature is the fluctuation in the measured impedance, which is always associated with living cells and persists even if the cell layer becomes fully confluent. This behavior is attributed to vertical motions or micromotions of the cells, an indication of cell viability and morphology change. ECIS presents a novel way to assess wound healing and serves as an alternative to animal testing for drug screening and toxicology studies. The size of the electrode can be reduced to 25-50 μm to open up an exciting possibility for monitoring single cell events. Microfabrication will allow up to several hundred different individual culture wells containing the detecting electrodes to be fabricated on a single chip. In this context, the methodology becomes a truly powerful and high throughput analytical device.