Polarization-Sensitive Optical Coherence Tomography to Study Diffusion of Plasmonic Gold Nanorods- a Novel Tool for Optical Bioimaging

Optical Coherence Tomography (OCT) is an imaging tool that performs micron-resolution, non-invasive, cross-sectional imaging by measuring the echoes of backscattered light. In this thesis, a custom-designed polarization-sensitive OCT (PS-OCT) system is discussed, which is implemented in using plasmonic gold nanorods (GNRs) as diffusion probes. PS-OCT imaging is undertaken in Newtonian fluids and validation of rotational and translational diffusion of GNRs with the Stokes-Einstein relation is presented via analysis of the autocorrelations of the OCT signals. Diffusion of GNRs in non-Newtonian fluids is also studied and the frequency-dependent viscoelasticity is also explored using generalized Stokes-Einstein relation. Furthermore, diffusion of GNRs in the "correlation length >= probe" regime is discussed in low concentration polymer solutions. Biological samples such as porous extracellular matrix (ECM) and in vitro mucus are explored using PEGylated GNRs as diffusion probes with PS-OCT imaging. The diffusion of GNRs was found to be sensitive to changes in the ECM induced either by ECM-remodeling fibroblasts or by changes in the ECM concentration. In mucus, the diffusion of GNRs was observed to be slowed down by less than 7-fold compared to the solvent, suggesting that the GNRs are able to readily navigate between the mucus mesh and avoid being readily trapped, thereby illustrating the potential GNRs hold in drug-delivery across the mucus barrier to the epithelial layers in lung airways. The capability of OCT to map diffusing GNRs and speckle fluctuations resulting from other motile activities in biological samples is also presented. A longitudinal study of mammary epithelial cells cultured in 3D with fibroblasts, to study normal and pre-malignant architectural cues, carried out using the custom-designed OCT system is also presented in detail. The integration of PS-OCT imaging with the measurement of diffusing GNRs in biological samples enables OCT to perform functional imaging to supplement its excellent structural imaging capability. This thesis presents a platform for extending the reach of OCT imaging to the exciting fields of microrheology and bio-rheology, which holds tremendous promise in the assessment of micro- and nano- scale viscoelasticity of biological samples using GNRs as probes.Doctor of Philosoph