Analyte Detection Schemes Using Functionalized Nanomaterials and Surface-Enhanced Raman Scattering

Controlling the nanoparticle surface environment is integral for precise drug-delivery systems, selective molecular-capture methods, and analytical techniques relying on plasmon resonance amplification, such as surface-enhanced Raman scattering (SERS). Despite the scientific community’s widespread interest in nanotechnology, few commercial products employ nanomaterials in disease diagnostics and therapeutics. One reason for this is the lack of shelf-stable and robust ligands that will remain adhered to the nanoparticle in complex, physiological environments. Thiol ligands are the current standard for functionalizing metal nanoparticle surfaces, particularly silver and gold. A rich chemistry toolkit has been developed for attaching biomolecules to nanoparticles via thiols. Thiol ligands, however, are prone to degradation via oxidation in ambient conditions and biologically relevant conditions. The first section of this dissertation introduces an alternative ligand for nanoparticle systems: N-heterocyclic carbenes (NHCs). In this section, we demonstrate the robustness of NHC ligands on a variety of gold surfaces with thorough characterization of the NHC-gold interaction using SERS, x-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). In addition, we develop a benchtop method for appending NHCs to aqueous nanoparticles without the need for air-sensitive techniques or external reductants. For the first time, we employ amide coupling on a nanoparticle surface using an NHC ligand and track the reaction sequence at each step with SERS, supplemented by theoretical calculations. Last, we perform foundational stability studies of the NHC-Au interaction in five commonly used biological media and demonstrate that an imidazolinium NHC motif may provide enhanced stability in extreme acidic environments.

Handling large data sets with SERS presents many challenges given the complicated nature of the spectra and the common need to focus the laser on nanoparticle aggregates for optimized signal. The second section of this dissertation focuses on the construction of a metabolite spectral database for metabolomics studies using SERS. We present SERS spectra for 63 metabolites from a commercially available set of standards. In addition, we introduce a targeted analysis approach which could be employed in the future to handle large data sets for SERS studies.

The last section briefly discusses a citizen science project, U-Watch, aimed at engaging middle school students with an authentic scientific investigation. In this case, we were interested in studying trace heavy metal contamination in drinking water from many geographical regions in the continental United States. In addition, U-Watch was the first citizen science project to employ a teacher residency program to develop an audience-appropriate curriculum package.