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Detecting and identifying infectious agents and potential pathogens in complex environments and characterizing their mode of action is a critical need. Traditional diagnostics have targeted a single characteristic, e.g. spectral response, surface receptor, mass, intrinsic conductivity, etc. However, advances in detection technologies have identified emerging approaches in which multiple modes of action are combined to obtain enhanced performance characteristics. Particularly appealing in this regard, electrophotonic devices capable of coupling light to electron translocation have experienced rapid recent growth and offer significant advantages for diagnostics. In this chapter, we explore three specific promising approaches that combine electronics and photonics: (a) assays based on closed bipolar electrochemistry coupling electron transfer to color or fluorescence (b) sensors based on localized surface plasmon resonances, and (c) emerging nanophotonics approaches, such as those based on zero-mode waveguides and metamaterials.