Engineering the Surface Chemistries of Plasmonic Nanoparticles for Biosensing Applications

Plasmonic nanoparticles (PNs) have unique optical properties that make them particularly attractive for biosensing applications. These properties arise due the localized surface plasmon resonance (LSPR) on their surface which occurs upon light excitation that is typically in the visible region of the electromagnetic spectrum. The absorbing and scattering properties of PNs are derived from the LSPR and are tunable based on the nanoparticle shape, size, and local dielectric environment. Furthermore, the LSPR on PNs enables fluorophores in close proximity (<10 nm) to be quenched through a nanosurface energy transfer (NSET) mechanism. In this dissertation, PNs are utilized to construct three novel biosensing modalities: The first by modulating the shape of PNs in response to enzyme inhibitors; the second by controlling the aggregation state of PNs in response to enzymes that are upregulated in cancers; and the third by turning “on” and “off” the fluorescence of dyes ligated to PNs in response to cell-death signaling enzymes. Specifically, in chapter one the optical properties of plasmonic gold nanorods (AuNRs) are explored in the context of their aspect ratio (length/width) to construct a colorimetric sensor. The LSPR of the AuNRs was highly sensitive to changes in aspect ratio and resulted in a visible color change in solution when incubated with a trypsin inhibitor. The second chapter shows how gold PNs with a thin layer of silver change color in different aggregation states. The aggregation state was determined by how much the PN crosslinker, a cysteine containing peptide/substrate, was digested by trypsin. In chapter three, the surface chemistry of gold nanoparticles is engineered to present self-assembling, coiled-coil peptides. One of the coiled-coil peptides in the pair on the PN surface was conjugated with a fluorophore and turns “on” once released upon digestion by the enzyme caspase-3