Transepidermal delivery and diffusion of optical skin clearing agents for reduction of light scattering in biological tissue and its clinical applications

The research results contained in this dissertation relate to the novel field of engineered tissue optics. Biological tissue such as skin is highly opaque due to multiple light scattering. However, it has been shown that certain hyper-osmotic chemicals can temporarily render turbid tissues such as skin optically transparent by reducing light scattering. The mechanisms involved in this process are believed to be a combination of dehydration and index matching. In order to capitalize on the non-invasive nature of light-tissue interactions for diagnostic and therapeutic purposes, hyper-osmotic optical clearing agents need to be delivered transepidermally. The first part of this dissertation is devoted to investigation of different methods to temporarily reduce the natural skin barrier posed by the stratum corneum in order to allow topically applied optical clearing agents to diffuse into epidermis and dermis. Methods such as needle-free injection gun, micro-needles, Er:YAG surface ablation, use of a 980 nm diode laser and mild surface abrasion using sandpaper were investigated. The second part of this dissertation investigated the effects of optical tissue clearing on tissue structure and influence on blood flow. Various imaging modalities such as optical coherence tomography (OCT), microscopy, confocal microscopy as well as transmission electron microscopy were employed to deduce how tissue structural changes can explain the temporary reduction of light scattering.