A holy grail in point-of-care diagnostics is to develop tests that perform on par with the central laboratory, in terms of robustness, multi-analyte capability, precision, and sensitivity. Oxonica has developed a series of nanoscale optical detection tags based on surface enhanced Raman scattering (SERS) that can potentially meet these criteria. These glass-coated, molecule-loaded gold nanoparticles are excited in the near-infrared, allowing detection in whole blood, and as many as a dozen different types can be simultaneously quantified using a handheld reader. Construction and optimization of these novel nanomaterials comprise classic problems in surface chemistry; the first half of this talk will focus on the techniques and tools we have used to prepare what are arguably the most robust and well-characterized SERS substrates ever made. The second half of the talk will focus on several diagnostic applications. (1) As a proof-of-concept, we have developed a multiplexed, quantitative lateral flow immunoassay (LFI) for Flu A, Flu B, and RSV. (2) We have developed an in-the-tube, no-wash assay for cardiac markers, and evaluated performance in serum, plasma, and whole blood. (3) We have demonstrated in vivo imaging of SERS nanotags in live animals. These applications underscore the range of possibilities opened up by chemical control of optical properties at the nanoscale.