Instantaneous, quantitative single-cell viability assessment by electrical evaluation of cell membrane integrity with microfabricated devices

Cell viability determination is an important process in life science. The loss of physical integrity in the plasma membrane is one of the major indications of cell death. Cell viability is thus usually determined through examination of membrane integrity with colorometric or fluorescent dyes. It occurred to us that when cell membrane loses the ability to exclude macromolecule dyes, its permeability to ions should also change, which could result in change in the electrical properties of the cell membrane. Therefore, evaluating the electrical properties of cell membrane should provide an indication on membrane integrity. We have designed and fabricated a chip to measure electrical currents that flow through single cells. For the purpose of detecting cell viability, the electrical measurements were correlated with conventional fluorescent dye assays that are typically used to distinguish between dead and live cells. Our experiments on human prostate carcinoma cells demonstrated that the electrical currents flow through live cells and membrane-impaired cells were substantially different., The dynamic processes of cell damage induced by various concentrations of Triton X100(TM), a cell lysing compound, have also been investigated. Our experimental results suggest that evaluation of cell membrane integrity by electrical measurements provides a simple, quantitative and instantaneous method for cell viability determination, which could be very useful in fundamental cell death study as well as cell-based biosensors for toxic-detection. (C) 2003 Elsevier Science B.V. All rights reserved.