This dissertation describes the design, fabrication and testing of an oblique incidence diffuse reflectance spectrometry (OIDRS) system for in-vivo and noninvasive detection of epithelial cancer. Two probes were fabricated using micromachining technology, which plays a significant role in the probe development by enabling device miniaturization, low-cost fabrication and precise assembly. The fist probe was developed and clinically tested for skin cancer detection. This probe consists of three source fibers, two linear array of collection fibers and four micromachined positioning devices for accurate alignment of the fibers. The spatially resolved diffuse reflectance spectra from 167 pigmented and 78 non-pigmented skin abnormalities were measured and used to design a set of classifiers to separate them into benign or malignant ones. These classifiers perform with an overall classification rate of 91%. The absorption and reduced scattering coefficient spectra were estimated to link the anatomic and physiologic properties of the lesions with the optical diagnosis. The melanoma cases presented larger average absorption and reduced scattering spectra than the dysplastic and benign ones. A second probe was designed to demonstrate the feasibility of a miniaturized ?side viewing? optical sensor probe for OIDRS. The sensor probe consists of a lithographically patterned polymer waveguides chip and two micromachined positioning substrates. This miniaturize probe was used to measure twenty ex-vivo esophageal samples. Two statistical classifiers were designed to separate the esophageal cases. The first one distinguishes benign and low dysplastic from high dysplastic and cancerous lesions. The second classifier separates benign lesions from low dysplastic ones. Both classifiers generated a classification rate of 100%.

<p>The visible wavelength range has proven to be a useful spectral window for observing biophotonic events such as absorption in materials (oxy-hemoglobin and deoxy-hemoglobin), light scattering in biological tissue, and biochemical and fluorescence reactions. Diffuse reflectance spectroscopy (DRS) is a technique that utilizes the diffuse reflectance spectra from turbid media (e.g. biological tissue) to quantify the optical properties (e.g. absorption and scattering) of those media. DRS in the visible wavelength range can be utilized to optically differentiate between healthy and cancerous tissue, and thus has applications in intra-operative tumor margin assessment. </p><p>The footprint of conventional DRS systems used for intra-operative tissue margin assessment prohibits their widespread use inside the surgical suite, where space is at a premium. Conventional quantitative DRS imaging systems utilize unwieldy fiber probes, cooled CCD cameras, and imaging spectrographs for imaging tissue margins. These system components not only increase system size, limiting their use inside the surgical suite, but also limit imaging resolution, imaging speed, and increase overall system cost. </p><p>Silicon is an attractive candidate for the development of compact, customized photodetector elements for biophotonic imaging applications such as intra-operative tumor margin assessment using DRS. This thesis deals with the design and development of a customized DRS imaging probe composed of custom silicon imaging arrays for intra-operative breast tumor margin assessment. The first generation of the customized imaging probe consisted of a 4x4 array of annular epitaxial Si pn junction photodiodes (PDs) with a measured responsivity of 0.28 A/W - 0.37 A/W for &#955;= 470 nm - 600 nm, and a measured dark current density of 1.456 nA/cm2 - 4.48 nA/cm2. The imaging array was used to detect diffuse reflectance when placed in direct contact with tissue. A quartz light delivery tube coupled to a xenon lamp was optimized to deliver light to the tissue through the holes of the annular imaging array across a 256 mm2 imaging area. The pixel-to-pixel spacing in the imaging array was 4.5 mm, the highest resolution reported to date for a multi-pixel DRS probe. This resolution was limited by pixel-to-pixel optical crosstalk, which was theoretically calculated and experimentally characterized, to validate the theoretical model for future designs. This first generation probe was successfully tested on diffuse reflectance standards, tissue-mimicking phantoms, animal tissue, and human breast tissue, and yielded an SNR of 30 dB - 55 dB on all measured specimens. </p><p>The next generation of the customized imaging probe consisted of a 4x4 array of annular thin-film Si pn junction PDs heterogeneously bonded to a transparent Pyrex substrate, to enable integration with a guided wave light delivery system. The 4x4 thin-film PD array design and development was prototyped using a 1x2 thin-film PD array heterogeneously bonded to a Pyrex substrate. The responsivity and dark current of the thin-film PDs in the 1x2 array were measured to be 0.19 A/W - 0.34 A/W for &#955;= 470 nm - 600 nm and 0.63 nA/cm2, respectively. The process for the 1x2 thin-film PD array was scaled to fabricate a 4x4 array of thin-film PDs for DRS, and the 4x4 array was optically and electrically characterized. These heterogeneously bonded thin-film single crystal Si PDs have the highest uncooled responsivity to dark current density ratio (greater than 0.30 - 0.54 cm2/nW for &#955;= 470 nm - 600 nm) reported to date, to the best of our knowledge. The 1x2 array of thin-film PDs were also heterogeneously bonded to a flexible substrate without any degradation in PD optical and electrical characteristics, opening the door towards conformal tissue imaging.</p> / Dissertation

The study of surface and interface structure of thin film devices is becoming increasingly important in industrial applications today. In this thesis, the technique of grazing incidence x-ray scattering (GEXS) is developed and its validity examined for many different materials. In addition, the technique of Born wave analysis introduced by Lagally has been extended, showing that in certain cases surface roughness can be obtained without full simulations of the data. GEXS measurements performed on float glass revealed that the density of the tin and air sides were 2.7 ± 1 and 2.3 ± 1 g/cc respectively across the entire ribbon. For all samples studied a surface layer on the order of a few nanometers was in evidence. When similar measurements were made on container glass it was seen to be layer free. In addition, excellent agreement was found between the roughness deduced from the simulations and the Born wave analysis. In all samples, the surface roughness deduced from the diffuse scatter was less than that from the specular, indicating that a vertical density gradient was present. When x-ray scattering measurements were performed on CVD layers deposited on glass it was noted that two sets of Yoneda wings existed in the diffuse scatter. From these it was concluded that lateral density variations existed in the SnO(_2) layer which were on the order of 0.5mm in diameter. Furthermore, excellent specular simulations were obtained. These indicated that the control of both layer thickness and interface roughness between samples was on the Angstrom level. Specular and diffuse x-ray scattering measurements were performed on Cu/Co multilayers grown on sapphire using a Nb buffer. Here the effect of anomalous dispersion was employed in order to highlight the scattering from the Cu/Co interfaces. From these data Born wave analysis was used to characterise the roughness of the samples. It was found that little change took place for anneals of 45 minutes at temperatures up to 300 C. In addition, it would appear that the measured OMR bore no relationship to the component of uncorrelated roughness within the samples. GIXS measurements perfumed on Cu/Co multilayers grown on Si, using a Cu(_3)Si buffer, revealed an asymmetry in the diffuse scatter, which was attributed to terracing within the layers. Simulations were obtained to the data using a slight modification of the fractal model for several scattering vectors with a single set of parameters. From this, a model of step bunching has been proposed which allows the diffuse scatter to be described using such a fractal surface. Diffuse x-ray scattering studies performed on Al(_2)O(_3), which had been ground in different ways, indicted that the surface density as measured from the Yoneda wings followed the bearing area as measured from optical techniques. Comparisons performed between these results and those from optical microscopy and surface acoustic wave techniques allowed a model to be proposed which was consistent with all the findings. Finally, GIXS measurements were performed on GaAs which had been subjected to various polishing techniques. Simulations revealed that a nanometer scale surface layer was present on all samples. Born wave analysis was successfully applied to the diffuse scatter and the effect of surface layers on the deduced roughness was investigated. In addition, symmetric and asymmetric triple axis diffraction studies revealed that the distribution of strains was independent of the type of polishing used whereas the tilts were not. A model has been proposed in which the surface consists of unstrained mosaic blocks separated by cracks.

Neutrino astronomy has the potential to greatly improve our understanding of the high-energy universe. An unresolved, diffuse, flux of neutrinos is sensitive to the properties of the population of cosmic accelerators in the universe. Data from 2008 and 2009 collected with the IceCube in-ice detector in a 40-string configuration were searched for an all-flavor ultra high-energy diffuse flux of astrophysical neutrinos. Data were divided into three streams based on signal and background event topology. Robustness was prioritized and a good agreement between real and simulated background data was observed. The search was optimized to give a high sensitivity to a neutrino flux with energy spectrum E-2 and energy greater than 1 PeV. The data sample used in the search for signal had a live time of 345.7 days and the estimated background was 1.2 ± 0.5 events. Taking systematic and statistical uncertainties into account, the sensitivity ΦS was estimated at E2 ΦS = 1.15 · 10-8 GeV cm-2 s-1 sr-1 assuming a 1:1:1 ratio between neutrino flavors at Earth. The full data sample was unblinded once the analysis procedure was fixed and approved by the IceCube collaboration. Three events survived the final filter level. The surviving events look like reasonable neutrino candidate events. Assuming a background only hypothesis, the probability of seeing three or more events is 10%. The resulting 90% confidence level upper limit ΦUL is the most strict to date with E2 ΦUL = 2.32 · 10-8 GeV cm-2 s-1 sr-1. The central 90% signal energy interval is 282 TeV to 214 PeV, and signal acceptance is distributed as 32% muon neutrinos, 39% electron neutrinos and 29% tau neutrinos. Several models for a diffuse extragalactic neutrino flux were excluded.

Univ., Diss.--Hannover, 1996.

Up to 20% of breast cancer patients who undergo presurgical (neoadjuvant) chemotherapy have no response to treatment. Standard-of-care imaging modalities, including MRI, CT, mammography, and ultrasound, measure anatomical features and tumor size that reveal response only after months of treatment. Recently, non-invasive, near-infrared optical markers have shown promise in indicating the efficacy of treatment at the outset of the chemotherapy treatment. For example, frequency domain Diffuse Optical Spectroscopic Imaging (DOSI) can be used to characterize the optical scattering and absorption properties of thick tissue, including breast tumors. These parameters can then be used to calculate tissue concentrations of chromophores, including oxyhemoglobin, deoxyhemoglobin, water, and lipids. Tumors differ in hemoglobin concentration, as compared with healthy background tissue, and changes in hemoglobin concentration during neoadjuvant chemotherapy have been shown to correlate with efficacy of treatment. Using DOSI early in treatment to measure chromophore concentrations may be a powerful tool for guiding neoadjuvant chemotherapy treatment. Previous frequency-domain DOSI systems have been limited by large device footprints, complex electronics, high costs, and slow acquisition speeds, all of which complicate access to patients in the clinical setting. In this work a new digital DOSI (dDOSI) system has been developed, which is relatively inexpensive and compact, allowing for use at the bedside, while providing unprecedented measurement speeds. The system builds on, and significantly advances, previous dDOSI setups developed by our group and, for the first time, utilizes hardware-integrated custom board-level direct digital synthesizers (DDS) and analog to digital converters (ADC) to generate and directly measure signals utilizing undersampling techniques. The dDOSI system takes high-speed optical measurements by utilizing wavelength multiplexing while sweeping through hundreds of modulation frequencies in tens of milliseconds. The new dDOSI system is fast, inexpensive, and compact without compromising accuracy and precision.

Made available in DSpace on 2014-06-11T19:29:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-10-23Bitstream added on 2014-06-13T20:19:25Z : No. of bitstreams: 1 faria_mlvc_me_botfm.pdf: 1185934 bytes, checksum: 4bb33f2f589bd619c63c31dc300156d7 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O problema que motivou esse trabalho foi a dificuldade, por parte dos profissionais da saúde, em acolher o sofrimento psíquico nas Unidades Básicas de Saúde (UBS) e nas unidades da Estratégia de Saúde da Família (ESF). Neste trabalho investigamos se esta dificuldade se deve a inadequação epistemológica do paradigma vigente na medicina para lidar com estas questões. Usando uma metodologia baseada em revisão de literatura tradicional, analisamos a utilização do termo paradigma na produção científica brasileira dos últimos dez anos, armazenada na base de dados SciELO. Após busca pelas palavraschave paradigma e medicina e seleção prévia, 17 textos foram escolhidos. Realizamos então análises linguísticas e um levantamento da temática emergente. A análise linguística foi realizada através do levantamento da frequência de uso de termos relevantes nos textos e do grafo de co-ocorrências construído utilizando estes termos. Posteriormente os artigos foram organizados conforme seu foco principal, em três grupos: teórico, ensino médico e prática médica. Levantou-se então a temática emergente de cada grupo. Os textos discutiram algumas das ideias de Kuhn, enfatizando características do paradigma médico hegemônico, sinais de crise desse paradigma e a necessidade de um novo paradigma para lidar com as demandas da atenção primária. Vários artigos apresentaram experiências inovadoras implantadas em Unidades de Saúde e exemplos de mudanças nos currículos de cursos de medicina. O sofrimento psíquico é reconhecido como anomalia paradigmática e a integralidade é caracterizada como um problema epistemológico para o paradigma vigente. As bases teóricas do SUS podem ser consideradas como uma revolução científica, no acepção de Kuhn. A promoção da saúde é um novo e promissor paradigma pois enfatiza a integralidade do cuidado, a prevenção... / The motivation for this work was the difficulties faced by health professionals to treat patients with psychic suffering in Health Basic Units (HBU) and in Strategies for Family Health. In this work, we investigate if these difficulties were due to epistemological deficiencies of the present medicine paradigm. Using a methodology based on bibliographic review, we analyzed the use of the word paradigm in Brazilian scientific articles in SciELO database on the last ten years. Initially we browsed for the keywords: paradigm and medicine and selected 17 texts. We then performed some computational linguistic analyses: we measured the words frequency and constructed the co-occurrences graph of the 50 most commonly used words. Afterwards we organized the articles according to their focus in three classes: theoretical, medical education, and medical practice. We then determined the emerging themes for each class. The texts discussed some of Kuhn’s ideas and emphasized characteristics of the hegemonic paradigm for medicine, crisis signs for this paradigm and the need of a paradigm shift to deal with primary care. Several articles presented innovative experiences carried out on Health Units and examples of changes on the curricula of medicine courses. The psychic suffering is considered a paradigmatic anomaly and integrality is characterized as an epistemological problem to the present paradigm. The Unified Health System (UHS) theoretical basis can be considered a scientific revolution in Kuhn perspective. Health promotion is a new and promising paradigm since it emphasizes integrality in the medical care, prevention, and commitment with quality of life and stimulates the community participation. Our analysis shows that the authors are of the opinion that many of the challenges faced by Brazilian health system are originated from epistemological questions. Although UHS is a theoretical breakthro... (Complete abstract click electronic access below)

Carbon fiber based composites are an essential material in weight-critical applications such as in the aerospace industry. However, these materials are susceptible to damage such as matrix microcracking and fiber/matrix debonding (diffuse damage), which occurs at stresses much lower than the failure stress. A T700/M21 [0/90]s laminate was tensile loaded to introduce diffuse damage and prepared for a study on the initiation of transverse microcracks. The material was tensile loaded in a [+45/-45]s orientation to induce diffuse damage. A diffuse damage indicator was developed by measuring the decrease in shear stiffness. Samples with diffuse damage levels of 0, 0.05, 0.10, 0.15, 0.20, and 0.25 were prepared to be tensile tested in a [0/90]s orientation to induce microcracks. A successful development of the microcracking test procedure was performed. The edge of the material was studied with optical microscopy and x-ray to establish the structure of the fiber bundle geometry when undamaged. A sample containing microcracks was treated with diiodomethane dye penetrant, which successfully highlighted microcracks during x-ray imaging. The application time was not sufficient to produce consistent x-ray images over time, so a 45 minute soak time was recommended instead. The same damaged sample was subjected to a tomographic scan without a dye penetrant and while unloaded. Transverse microcracks were successfully identified from the data, although the results were not clean enough and likely omitted some smaller microcracks. Results are expected to be cleaner if performed during tensile testing. Future tensile testing will quantify the induced crack density of samples containing various degrees of initial diffuse damage, either using x-rays with a dye penetrant or using x-ray microtomography.

No description available.

Optical biopsy is a medical technique that uses light to perform non-invasive analysis of tissue in-situ. This technology has many applications in the medical profession, opening up exciting new possibilities for surgical guidance and diagnosis of malignancies and other conditions. Optical biopsy allows a medical professional to perform near instantaneous, real time analysis of tissue composition without the need to physically remove tissue from the body, as required in traditional biopsy. A technique frequently used for this purpose is diffuse reflectance spectroscopy (DRS): collection and analysis of the spectrum of light reflected from a material. Another technique frequently used for optical biopsy is laser induced fluorescence spectroscopy (LIFS): analysis of the fluorescence spectrum returned by a material when illuminated at a specific wavelength. This thesis discusses the design and construction of a spatially resolved DRS system intended for use in a dual modality DRS and time resolved LIFS optical biopsy instrument for clinical analysis of brain tissue. This instrument is specifically intended for use in the surgical removal of malignant gliomas: infiltrating tumours associated with a poor patient prognosis. Theoretical simulation based studies were used to optimize the design of a compact, dual modality fibre optic probe for use in the system and a novel algorithm was developed to allow recovery of the optical properties of tissue from reflectance spectra obtained with this probe. This probe was manufactured and a corresponding spectrometer based system was created for the acquisition of diffuse reflectance spectra. Components were designed to allow sterilization and thus clinical use in an operating room environment. A laboratory trial of this system demonstrated its range and ability to recover the optical properties of lipid emulsion optical phantoms. / Thesis / Doctor of Philosophy (PhD)