Plasmon resonance coupling as a tool for detecting epidermal growth factor receptor expression in cancer
Optical molecular imaging has burgeoned into a major field within biomedicine, and technologies that incorporate surface plasmon resonance effects have become a major focus within this field. Plasmon resonance has been defined as the collective oscillation of the conduction band electrons in certain metals (such as gold) in response to an electric field, such as an impinging wave of light. We show that elastic light scattering due to the plasmon resonance of nanometer-sized gold particles makes them powerful tools for optical imaging of epidermal growth factor receptor (EGFR) expression -- a major biomarker for carcinogenesis. Optical technologies in general are poised as cheap, flexible ways to aid in diagnosis and treatment of disease. In addition to supplying a bright, stable optical scattering signal and a convenient conjugation platform for targeting molecules, these materials display a unique behavior termed "plasmon coupling". This term refers to the dramatic optical property changes brought about by the presence of other nearby nanoparticles. These changes include a dramatic red-shifting in their peak plasmon resonance wavelength, as well as a non-linear, per-particle increase in the overall scattered power. We show that such conditions exist in cells and are primarily due to intricate protein trafficking mechanisms as part of the EGFR life-cycle. The observed variations in plasmon coupling can give clues as to the nanoscale organization of these important proteins. In addition, the resulting optical property changes result in a large, molecular-specific contrast enhancement due to the shifting of the resonance closer to the near infrared region, where biological tissues tend to be most transparent. Despite this enhancement, however, many tissues contain large endogenous signals, as well as barriers to delivery of both light and the nanoparticles. As such, we also show an example of a multifaceted approach for further increasing the apparent molecular-specific optical signals in imaging of EGFR expression by using an oscillating magnetic field. This serves to encode the signal from magnetically susceptible plasmonic nanoparticles, making their extraction from the background possible. Overall, the studies presented in this dissertation should serve to stimulate further investigations into a wide variety of technologies, techniques, and applications.