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Strategies for Enabling Surface-Enhanced Raman Spectroscopy of Small Human Performance Biomarkers

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Surface-enhanced Raman scattering (SERS) spectroscopy has been demonstrated to be a powerful analytical tool. Its chemical specificity, rapidity, and portability make it an attractive technique for biosensing, but its application to this field has been limited by the fundamental distance dependence of the surface-enhancement effect. Many biological molecules of interest do not spontaneously adsorb to noble metal nanostructures, excluding them from the scope of molecules that SERS can interrogate. This dissertation addresses two ways to circumvent this limitation and detect, by SERS, small biological molecules relevant to human performance: 1) the use of noble metal-affinitive capture agents that either bring the molecule of interest close to the surface-enhancing substrate or act as spectral indicators of analyte capture, and 2) physicochemical trapping by polymer-halted nanoparticle aggregation. The successful SERS detection by physicochemical trapping of dopamine, epinephrine, norepinephrine, serotonin, and histamine is reported, as is a generalizable protocol for detecting weakly metal-affinitive molecules by SERS with a high signal-to-noise ratio and spectral consistency into nM concentrations. The suitability of seven capture agents for cortisol and one for dopamine for SERS was evaluated. None enabled SERS detection of their respective analytes. The results instead led to insights into the sensitivity of the capture agents and recommendations for successfully implementing single-stranded DNA aptamers as SERS capture agents for the detection of small molecules.

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