PROJECT SUMMARY Electrical activities in cells play key roles in many important biological processes, including brain signal pro- cessing, cardiac functions, wound healing and other developmental processes. Currently, the most widely used experimental tool for studying the cellular electrical activities measures a local electrical current or voltage with a microelectrode or micropipette. While sensitive, it lacks spatial resolution and can be invasive. Developing a non-invasive and sensitive technology that can image small electrical signals in cells with high spatial and tem- poral resolutions has been a long-standing goal. This renewal project develops a plasmonic-based electrical impedance microscope (P-EIM) for label-free imaging of electrical signals in cells. The microscope converts an electrical signal to a plasmonic signal, which is imaged optically. Building on the success of substantial prelimi- nary studies, the PI propose to develop a new capability of P-EIM for studying cellular electrical activities, vali- date its performance using reference technologies, and establish key applications, including imaging action potential propagations in neurons, drug induced ion channel activity changes, and potential distributions in cells during wound healing processes. The success of this project will lead to a new tool for studying electrical activities in cells with temporal and spatial resolutions that are not possible with the existing technologies. This new label-free imaging tool will provide new insights into the roles of electrical activities in biological processes, and a new method for screening drugs targeting neuronal and cardiac functions, wound healing and other de- velopmental processes.