Described are interdigitated electrodes, which may optionally be plasmonic, useful for in vitro biosensing applications. Such devices may significantly reduce undesired background noise by separating the excitation source (light) from the detection signal (current), and thereby, leading to higher sensitivity for bioanalysis compared with conventional interdigitated electrodes. Also described are methods of making such interdigitated electrodes, which allow a substrate, which may optionally be plasmonic, to be tuned not only to maximize the targeted interaction of the cells with the nanoscale geometry, but also for the excitation wavelength to minimize biological sample interference.