Electrochemical cellular biosensor combined with fluorescence microscopy: An investigation of subtle changes in response of cells to a drug

Abstract

This study presents the combination of electrochemical cell based biosensor and fluorescence microscopy on a single platform to track biomolecular processes contributing to the morphology changes of the cells. Initial experiments demonstrate that using interdigitated electrodes where the gold microfingers were comparable in width and spacing to a single cell have the optimal sensitivity in the final electrochemical cell based-sensing device. This was determined by measuring the cell index, based on the impedance analysis of bare and cell-covered microelectrodes. The fabrication of the electrodes on a glass substrate enabled the capture of high-resolution fluorescence microscopy images of single cells and related intracellular calcium release inside the HeLa cells via a window incorporated into the gold microelectrode design. As an illustration of the enhanced capability of the combined approach over traditional impedance cellular assay, the opto-electric assay was utilized as a functional readout for G protein couple receptor activation. The simultaneous examinations of cells stimulated with histamine demonstrated an association between time courses of changes in cytosolic calcium concentration and reductions in cell-cell adhesions.