The motivation of this study lies in the necessity for a microfocal therapy to specifically target diseased areas in vascular pathologies such as age-related macular degeneration (AMD). AMD is the most common cause of legal blindness among people over the age of 60 in developed countries. This degenerative condition affects the macula, the central region of the retina, severely impairing detailed vision and hindering everyday activities. Worldwide, 25-30 million people live with some form of AMD. Among them, ~10% suffer from the more advanced and damaging form, wet-AMD, which causes rapid and severe loss of central vision. To date, there is no cure or long-term alternative for this degenerative disease despite intensive research efforts. With recent developments in biophysical tools and experimental procedures, in this study, we demonstrate a highly-localized therapeutic option: two-photon (2-photon) photodynamic therapy (PDT) that could be advantageous for the cure of wet-AMD, either alone or in combination with recently discovered anti-angiogenic therapies. This new approach offers selective targeting of the diseased area, thus minimizing damage to the surrounding sensitive healthy eye tissues, which is a major concern with the clinically-used, standard wide-beam, one-photon (1-photon) PDT. The objective of the research was to test the feasibility of microfocal 1-photon and the inherently localized 2-photon PDT, their optimization and also to evaluate the efficacy of existing 1-photon and novel 2-photon photosensitizers. In this thesis, I illustrated the in vitro (endothelial cell monolayer) and in vivo (window chamber mouse (WCM)) models that can be used to quantitatively compare the 2-photon efficiency of photosensitizers. Using the in vitro model, I compared the 2-photon efficacy of clinically used 1-photon PDT drugs Photofrin and Visudyne, and showed that the Visudyne is an order of magnitude better 2-photon photosensitizer than Photofrin. With the WCM model, I demonstrated a novel designer 2-photon photosensitizer is 20 times more efficient than Visudyne for single vessel occlusion. I also generated the drug and light dose reciprocity curve for localized single-vessel microfocal PDT. This is a necessary step towards applying the method to the relevant ocular models of AMD, which is the next phase for this research.

Introduction: Currently, there are no objective techniques to assess burn depth. An early assessment of burn depth would enable accurate management decisions, which would improve patient outcomes. Near infrared (NIR) technology has shown promise as a non-invasive monitor of oxygenation and perfusion, and its potential to assess the depth of burn injuries has been investigated clinically over the past five years. The purpose of the thesis was to determine the capacity of NIR technology to differentiate acute thermal injuries. Methods: Burn sites (n=5) and control sites (n=5) were created on the dorsum of sixteen animals with brass rods held at constant pressure and heated to 100°C and 37.5°C respectively. NIR data was collected from the burns and control sites pre-burn, immediately post-burn, and 1, 12, 24, 36, 48 and 96 hours after the burn injury. Biopsies of the burn and control sites were acquired at each time point and used to confirm the depth of injury. NIR data was processed for the content of water, oxy-, deoxy- and methemoglobin. Results: Oxyhemoglobin and total hemoglobin decreased as burn depth increased. The proportion of oxy- and deoxyhemoglobin to total hemoglobin showed that the ratio of oxy- to deoxyhemoglobin decreased as burn injury increased. Methemoglobin levels as a ratio of total hemoglobin also showed that as the severity of injury increased the proportion of methemoglobin also increased. Finally, superficial partial thickness injuries (3 s and 12 s) showed early peak levels of water, which rapidly declined towards baseline. The deep partial thickness injuries (20 s and 30 s) do not experience peak levels and retain water over the course of the experiment. The full thickness injuries water levels remain close or below baseline levels throughout the experiment. Conclusion: NIR spectroscopy could distinguish burn depth using water, oxy-, met- and total hemoglobin as separate entities. The presence of methemoglobin in the burn wounds is a novel finding that has not been described previously in burn literature.

The study and applications of surface plasmon polaritons (SP) – also known as plasmonics – has attracted the interest of a wide range of researchers in various fields such as biology, physics, and engineering. Unfortunately, the large propagation losses of the SP severely limit the usefulness of plasmonics for many practical applications. In this dissertation a new wave guiding mechanism is proposed in order to address the large propagation losses of the plasmonic guides. Possible applications of this guiding scheme are also investigated. The proposed hybrid plasmonic waveguide (HPWG) consists of a metal layer separated from a high index slab by a low index spacer. A detailed analysis is carried out to clarify the wave guiding mechanism and it is established that the mode guided by the HPWG results from the coupling of a SP mode and a dielectric waveguide mode. A two dimensional HPWG is proposed and the effects of various parameters on the HPWG performance are analyzed in detail. This structure offers the possibility of integrating plasmonic devices on a silicon platform. The proposed waveguide supports two different modes: a hybrid TM mode and a conventional TE mode. The hybrid TM mode is concentrated in the low index layer, whereas the conventional TE mode is concentrated in the high index region. This polarization diversity is used to design a TM- and a TE-pass polarizer and a polarization independent coupler on a silicon-on-insulator (SOI) platform. Moreover, the performance of a HPWG bend is investigated and is compared with plasmonic waveguide bends. The proposed devices are very compact and outperform previously reported designs. The application of HPWG for biosensing is also explored. By utilizing the polarization diversity, the HPWG biosensor can overcome some of the limitations of plasmonic sensors. For example, unlike plasmonic sensors, the HPWG biosensor can remove the interfering bulk and surface effects.

Quantum cryptography, or quantum key distribution (QKD), provides a means of unconditionally secure communication. The security is in principle based on the fundamental laws of physics. Security proofs show that if quantum cryptography is appropriately implemented, even the most powerful eavesdropper cannot decrypt the message from a cipher. The implementations of quantum crypto-systems in real life may not fully comply with the assumptions made in the security proofs. Such discrepancy between the experiment and the theory can be fatal to the security of a QKD system. In this thesis we address a number of these discrepancies. A perfect single-photon source is often assumed in many security proofs. However, a weak coherent source is widely used in a real-life QKD implementation. Decoy state protocols have been proposed as a novel approach to dramatically improve the performance of a weak coherent source based QKD implementation without jeopardizing its security. Here, we present the first experimental demonstrations of decoy state protocols. Our experimental scheme was later adopted by most decoy state QKD implementations. In the security proof of decoy state protocols as well as many other QKD protocols, it is widely assumed that a sender generates a phase-randomized coherent state. This assumption has been enforced in few implementations. We close this gap in two steps: First, we implement and verify the phase randomization experimentally; second, we prove the security of a QKD implementation without the coherent state assumption. In many security proofs of QKD, it is assumed that all the detectors on the receiver's side have identical detection efficiencies. We show experimentally that this assumption may be violated in a commercial QKD implementation due to an eavesdropper's malicious manipulation. Moreover, we show that the eavesdropper can learn part of the final key shared by the legitimate users as a consequence of this violation of the assumptions.

Pillar-array based optical cavities have unique properties, e.g., having a large and connected low dielectric index space (normally air space), exhibiting a large band gap for transverse magnetic modes, having a large percent of electric field energy in air and standing on a substrate. These properties make them well suitable for applications such as optical sensing and terahertz quantum cascade lasers. However there has been rare research in it due to the common belief that pillar arrays have excessive leakage to the substrate. With careful design, we provided several methods to reduce such a leakage and experimentally proved a high quality factor (Q) pillar-array based cavity is practical. We also explored the usage of such a cavity for optical sensing. Numerical methods such as finite-difference time-domain and plane-wave expansion were used in the design of the cavity. Then in microwave spectrum, cavities consisting of dielectric rods were used to test the validity of the theory. Additionally, we observed that a high-Q cavity for modes above light line is feasible and it is very suitable to measure the optical absorption of materials introduce inside the mode volume. Finally in the optical domain, pillar arrays were fabricated in Si/SiO2 material system and measured. Q as high as 27,600 was shown and when applying accurate refractive indices, for every delta n = 0.01, the peak wavelength shifted as large as 3.5 nm, testifying the ultra sensitivity of the cavity to the environmental dielectric change.

Conventional step-index silica fibers do not possess a second-order optical nonlinearity due to symmetry concerns. However, through the process of poling, the generation of a frozen-in DC field $E^{DC}$, and in turn, a non-zero second-order nonlinearity $\chi^{(2)} = 3\chi^{(3)}E^{DC}$, can be created in optical fibers. In this thesis, I measure the individual $\chi^{(2)}$ tensor elements of birefringent periodically poled fiber via second-harmonic generation and sum-frequency generation experiments. The symmetry of the $\chi^{(2)}$ tensor is consistent with that of the $\chi^{(3)}$ for isotropic media. This is the first study that characterizes all the $\chi^{(2)}$ tensor elements in birefringent poled fiber. Furthermore, I investigate the intermix of the $\chi^{(2)}$ tensor elements by twisting the fiber, which results in the generation of new second-harmonic signals not observed in untwisted fiber. The conversion efficiencies and spectral positions of these new signals can be varied by twisting the fiber.

Optical methods can provide useful tissue characterization tools. For this project, two-photon microscopy and polarized light examinations (polarimetry) were used to assess the organizational state of myocardium in healthy, infarcted, and stem-cell regenerated states. Two-photon microscopy visualizes collagen through second-harmonic generation and myocytes through two-photon excitation autofluorescence, providing information on the composition and structure/organization of the tissue. Polarimetry measurements yield a value of linear retardance that can serve as an indicator of tissue anisotropy, and with a dual-projection method, information about the anisotropy axis orientation can also be extracted. Two-photon microscopy results reveal that stem-cell treated tissue retains more myocytes and structure than infarcted myocardium, while polarimetry findings suggest that the injury caused by temporary ligation of a coronary artery is less severe and more diffuse that than caused by a permanent ligation. Both these methods show potential for tissue characterization.

Conventional step-index silica fibers do not possess a second-order optical nonlinearity due to symmetry concerns. However, through the process of poling, the generation of a frozen-in DC field $E^{DC}$, and in turn, a non-zero second-order nonlinearity $\chi^{(2)} = 3\chi^{(3)}E^{DC}$, can be created in optical fibers. In this thesis, I measure the individual $\chi^{(2)}$ tensor elements of birefringent periodically poled fiber via second-harmonic generation and sum-frequency generation experiments. The symmetry of the $\chi^{(2)}$ tensor is consistent with that of the $\chi^{(3)}$ for isotropic media. This is the first study that characterizes all the $\chi^{(2)}$ tensor elements in birefringent poled fiber. Furthermore, I investigate the intermix of the $\chi^{(2)}$ tensor elements by twisting the fiber, which results in the generation of new second-harmonic signals not observed in untwisted fiber. The conversion efficiencies and spectral positions of these new signals can be varied by twisting the fiber.

Optical methods can provide useful tissue characterization tools. For this project, two-photon microscopy and polarized light examinations (polarimetry) were used to assess the organizational state of myocardium in healthy, infarcted, and stem-cell regenerated states. Two-photon microscopy visualizes collagen through second-harmonic generation and myocytes through two-photon excitation autofluorescence, providing information on the composition and structure/organization of the tissue. Polarimetry measurements yield a value of linear retardance that can serve as an indicator of tissue anisotropy, and with a dual-projection method, information about the anisotropy axis orientation can also be extracted. Two-photon microscopy results reveal that stem-cell treated tissue retains more myocytes and structure than infarcted myocardium, while polarimetry findings suggest that the injury caused by temporary ligation of a coronary artery is less severe and more diffuse that than caused by a permanent ligation. Both these methods show potential for tissue characterization.

Quantum cryptography, or quantum key distribution (QKD), provides a means of unconditionally secure communication. The security is in principle based on the fundamental laws of physics. Security proofs show that if quantum cryptography is appropriately implemented, even the most powerful eavesdropper cannot decrypt the message from a cipher. The implementations of quantum crypto-systems in real life may not fully comply with the assumptions made in the security proofs. Such discrepancy between the experiment and the theory can be fatal to the security of a QKD system. In this thesis we address a number of these discrepancies. A perfect single-photon source is often assumed in many security proofs. However, a weak coherent source is widely used in a real-life QKD implementation. Decoy state protocols have been proposed as a novel approach to dramatically improve the performance of a weak coherent source based QKD implementation without jeopardizing its security. Here, we present the first experimental demonstrations of decoy state protocols. Our experimental scheme was later adopted by most decoy state QKD implementations. In the security proof of decoy state protocols as well as many other QKD protocols, it is widely assumed that a sender generates a phase-randomized coherent state. This assumption has been enforced in few implementations. We close this gap in two steps: First, we implement and verify the phase randomization experimentally; second, we prove the security of a QKD implementation without the coherent state assumption. In many security proofs of QKD, it is assumed that all the detectors on the receiver's side have identical detection efficiencies. We show experimentally that this assumption may be violated in a commercial QKD implementation due to an eavesdropper's malicious manipulation. Moreover, we show that the eavesdropper can learn part of the final key shared by the legitimate users as a consequence of this violation of the assumptions.