Call number: LD2668 .T4 1965 S535 / Master of Science

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This dissertation is divided into two separate parts covering my research in two different fields of optics. Part I consists of chapters 1-3 and covers experiments on periodically poled lithium niobate while Part II consists of chapters 4-6 and covers various spectroscopic methods designed for the application of in vivo blood analysis. Chapter 1 serves as a brief introduction to periodically poled lithium niobate and its fabrication process. In chapter 2, the key results of Part I, derived from a series of experiments on poling of thinned lithium niobate, are presented. Building upon these experiments, chapter 3 concludes Part I with a study on poling of crystal ion sliced lithium niobate. Part II begins with chapter 4, which describes a spectroscopic approach for non-invasive blood analysis in vivo. In chapter 5, experiments analyzing aqueous glucose solutions with mid-infrared and Raman spectroscopy are discussed. Chapter 6 concludes this dissertation with the design and demonstration of a innovative stimulated Raman spectroscopy system. In Part I, ferroelectric poling fabrication procedures were developed, optimized, and implemented for periodic poling of thinned lithium niobate. The free-standing samples of thickness from 500 μm down to 25 μm were thinned by chemical mechanical planarization and annealed before poling. Domain structure was investigated as a function of sample thickness using Raman, scanning electron, atomic force, and optical microscopy, and broadening of poled domains was consistently found to vary with sample thickness in a strong linear correlation. Domain broadening was reduced by 38% as the thickness of the poled sample was reduced from 500 to 25 μm. Micro Raman probe measurements showed a thickness-dependent contrast in Raman active mode intensity between poled and unpoled regions, with the thinner samples having a higher intensity contrast. To explore poling on even thinner free-standing samples, crystal ion sliced lithium niobate thin films of 10 μm in thickness were fabricated. Chemical mechanical planarization of the ion-implanted layer and annealing was performed to prepare the thin films for poling. Ferroelectric poling of the crystal ion sliced samples was attempted, but unsuccessful, suggesting that alternative fabrication processes may be necessary for poling of crystal ion sliced thin films. In Part II, several disparate experiments were conducted to progress towards a common overarching goal of developing a spectroscopic method for non-invasive whole blood analysis and metabolite monitoring. A portable visible and near-infrared spectroscopy system for in vivo blood spectral identification was developed and demonstrated in a clinical setting. A custom-designed clip attached the illumination and collection optics to opposite sides of the patients’ fifth fingertip, and applied gentle pressure, gradually pushing a small quantity of blood away from the measurement site, and inducing a time-dependent change in the effective path length of blood. Time-dependent visible and near-infrared spectra were measured from the collected transmitted and scattered light. A maximum likelihood model was developed to leverage the time-dependent spectral component and identify the spectrum of blood, isolating it from that of surrounding tissue. A second set of experiments were conducted to develop a model for predicting glucose concentrations from measured mid-infrared transmission and spontaneous Raman scattering spectra. Partial least squares regression models were trained, validated, and tested on the spectra of aqueous 0-10 mM glucose solutions measured by both spectroscopic modalies. The models proved to be accurate predictors of glucose concentration as the mean squared error of the model based on mid-infrared spectra ranged from 0.10 - 0.74 mM, and that of the Raman-based model ranged from 0.26 - 0.93 mM. Finally, an LED-based stimulated Raman system was innovated to improve upon the relatively weak spontaneous Raman signal in a cost-effective manner. Stimulated Raman gain using a broadband LED Stokes source was demonstrated in the measuring of vibrational spectra of aqueous 0-10 mM glucose solutions. Scattered light was detected via photomultiplier tube and measured using either a photon counter or a lock-in amplifier in two alternative versions of the system. Both stimulated and spontaneous Raman spectra were collected with each instrument for a total of four measurement modalities. The stimulated Raman spectra measured with the photon counter showed up to 100% higher intensity for some glucose modes compared to the corresponding spontaneous Raman spectra, but also had significantly greater noise. For the spectra measured with the lock-in amplifier, the glucose modes of the stimulated Raman spectra were only 20-30% higher in intensity than those of the spontaneous Raman spectra, but had similar levels of noise. Partial least squares regression models based on spectra measured by each modality were developed and compared. The model based on stimulated Raman spectra measured with the lock-in amplifier had the strongest predictive power of all modalities and predicted the concentrations of the aqueous 0-10 mM glucose solutions with a mean squared error as low as 9.96x10-4 mM, an order of magnitude lower than that of the model based on spontaneous Raman spectra.

M.S. / Applied Physics / A new method of measuring the level of 8-methoxypsoralen in blood serum was developed for the reasons of speed, accuracy, and cost. This new method uses laser induced fluorescence of the psoralen to determine the concentration in serum. The fluorescence is analyzed with an optical multichannel analyzer coupled to an intensified photodiode array detector. Research was first attempted on samples with ethanol as the solvent to confirm that the method would work. Sample concentrations of 8-methoxypsoralen in serum are determined by comparing the fluorescence signal obtained from previously known concentrations. Levels down to 200ng per milliliter of serum can be measured with this technique.

The arterioles of the cat sartorius muscle dilate when arterial pressure is reduced. It has been suggested that this dilation is due to a decrease in blood flow which in turn decreases oxygen delivery and increases tissue production of vasodilator substances. The latter diffuse into the vicinity of the arterioles and cause vascular relaxation. This vascular dilation acts to maintain blood flow through the tissue near the control level at a time when perfusion pressure is reduced. This phenomenon, called autoregulation of blood flow, has been observed in most organs of the body. In the following experiments, we attempted to test the hypothesis that a fall in the oxygen level of the tissue is responsible for blood flow autoregulation. We did this by studying the response of cat sartorius arterioles to arterial pressure reduction under conditions where the muscle was supplied with oxygen from the environment in addition to that normally supplied by the blood. Tissue PO₂ was altered by placing the isolated, auto-perfused cat sartorius muscle in contact with silicone fluid equilibrated with a 0% to 20% oxygen gas mixture. As oxygen tension in the bathing fluid was increased, the preponderant response was a decrease in arteriolar diameter, blood velocity and arteriolar volume flow. To illustrate, 8% of the arterioles constricted by an average of 10% and 18% when the muscle was exposed to oxygen tensions of 66 and 132 mmHg, respectively. When blood flow autoregulation was investigated, it was found that elevated oxygen tension in the bathing fluid abolished any significant arteriolar dilation or flow autoregulation in the majority of arterioles studied. In addition, the elevated oxygen environment caused complete cessation of blood flow in many of the smaller arterioles (< 15μ in diameter). The results of this study strongly suggest that the O₂ level of the tissue is an important determinant in local blood flow regulation.

In recent years the study of serum glycoproteins has advanced rapidly. Much of this interest in serum protein-carbohydrate complexes has been inspired by findings that many physiological and pathological conditions are associated with elevated serum protein bound carbohydrates. Paper electrophoFesis has been used in many studies of the serum glycoproteins of the human and experimental animals. Reports on the electrophoretic distribution of serum glycoproteins in most animals, however, are lacking. [...]

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Previous studies of serum adenosine deaminase have neglected consideration of the two molecular forms of this enzyme that exist in human tissues. The purpose of this study was to survey the distribution of these forms in normal and pathological human sera. Both molecular forms were present in normal serum, though the small form predominated. This form also predominates in lymphocytes, erythrocytes, and in tissues with high specific activity of this enzyme. The ratio of the two forms is different for plasma and serum and can change with sample storage. The activity of the small form varied over a wider range than the activity of the large form in normal serum. Many pathological samples showed an altered distribution of the two forms. This study demonstrates the potential usefulness of serum forms of adenosine deaminase for distinguishing some pathological conditions.

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The investigation was concerned with characterizing effects of this tumor line on lipid metabolism in DBA/1J mice and serum protein levels and cellular changes in DBA/1J and Swiss white mice. Total lipids, lipid phosphorus, neutral lipids, and changes in fatty acids were determined in liver, spleen, skin and tumor of DBA/1J mice bearing the lymphosarcoma at various days after injection of tumor cells.