Plasmon-enhanced ultrasensitive and minimally-invasive bio-diagnostics

Detection, imaging, and quantification of low abundant biomolecules within biological fluids, cells, and tissues is of fundamental importance but remains extremely challenging in biomedical research as well as clinical diagnostics. We have designed and synthesized an ultrabright fluorescent nanoconstruct, termed “plasmonic-fluor”, as an “add-on” bio-label to dramatically improve the signal-to-noise ratio of a wide variety of existing fluorescence bioassays without altering or complicating the conventional assay workflow or read-out devices. We demonstrate that these novel nanoconstructs can be readily utilized in a broad range of bioanalytical methods, including fluorophore-linked immunosorbent assays, multiplexed bead-based immunoassays, lateral flow assays, immuno-microarrays, flow cytometry, and immunocytochemistry, to attain more than 1000-fold improvement in the limit-of-detection and dynamic range. Harnessing plasmonic-fluors, we also demonstrate minimally-invasive and ultrasensitive quantification of target protein biomarkers in interstitial fluid through microneedle-assisted in vivo sampling and subsequent on-needle analysis.