The primary focus of the work described in this dissertation is the coupling of PEBBLE (Photonic Explorers for Biomedical use by Biologically Localized Embedding) nanosensors with new sensing technologies.

Included in this body of work is the application of fluorescence anisotropy based measurements to PEBBLE nanosensors, in order to measure analyte concentrations. The advantage of the fluorescence anisotropy technique is that it is a self-referencing measurement; therefore the process of designing fluorescence based nanosensors is streamlined. Separate measurements were performed on poly (acrylamide) PEBBLEs with embedded Calcium Green and Newport Green indicator dyes in order to sense Ca²⁺_(aq.) and Zn²⁺ _(aq.), respectively. A sol-gel PEBBLE with the embedded [Ru(dpp) ₃]²⁺ indicator dye was used to make O₂ measurements in a sealed gas-tight optical cell.

A second sensing technique investigated utilizes a new photoacoustic based sensing method that utilizes the pH-sensitive fluorescent indicator dye SNARF-5F. In the experiment, the photoacoustic response of a series of solutions, with the indicator dye dissolved in buffers that ranged in pH from 6 to 9, was consistent with the trend that one would expect based on the absorption of the SNARF-5F dye as a function of pH. This proof-of-principle experiment demonstrates the possibility of creating an in vivo nanoplatform for sensing analyte concentrations in whole, intact tissue using photoacoustic detection.

A silver nanoprism colloid was investigated as a potential Surface-Enhanced Raman Scattering (SERS) substrate, with the analyte 4-mercaptopyridine (4-MPy). This analyte was chosen as a test molecule because it could be utilized to develop a SERS based pH nanosensor with the nanoprism colloid. It had been discovered that, while the poly (vinyl pyrrolidone) (PVP) organic capping agent interfered with the acquisition of the SERS signal on the nanoprism colloid, this approach is feasible.