Project Summary Linking infectious agent diagnostics to clinical decision-making at the point-of-care, requires a fast, highly sensitive and simple to use method that takes into account the infrastructure and workflow in clinical settings of both developing and developed regions. In addition, being able to distinguish among multiple potential infectious pathogens in a single test is of great importance as many pathogens cause similar symptoms. The goal of this phase I proposal is to develop and validate a highly sensitive biosensor diagnostic platform allowing naked eye detection of viral antigens at ? 1pM concentration in human serum. Our initial focus will be on antigens from hemorrhagic fever viruses including Ebola and Dengue that are classified as Category A NIAID priority pathogens. The proposed diagnostic platform integrates three key features i) high efficiency capture and isolation of biomarkers ii) surface enrichment on sensing surfaces and iii) label-free naked eye detection at low concentrations. The sensitivity of the nanohole sensor is based on two important scientific discoveries: (i) Extraordinary Light Transmission (EOT) effect, and (ii) highly dispersive plasmonic Fano resonances that eliminates the need for powered operated light sources or optical detectors. Recombinant viral proteins spiked in commercially available human serum will be used to evaluate the sensitivity, specificity and reliability of this diagnostic platform. At the end of this phase I grant a working nanophotonic prototype will provide the basis for advancing this novel viral diagnostic platform for phase II development.