O presente trabalho trata-se do desenvolvimento de uma cavidade Laser de estado sólido e geração de segundo harmônico, para fins oftalmológicos. A cavidade faz parte de um projeto maior que se refere a um fotocoagulador portátil, utilizado em diversos protocolos clínicos relacionados às doenças da retina e câmara anterior, como retinopatia diabética, retinopatia da prematuridade, glaucoma, edema macular e descolamento de retina. A cavidade proposta é composta por três espelhos dispostos em uma arquitetura em V. Um laser de diodo bombeia um cristal de Nd:YAG para a geração de laser em 1064nm que passa por um cristal de KTP para a geração de segundo harmônico em 532nm (laser verde). O sistema de acoplamento indexado à cavidade acopla até 90% da potência de saída em uma fibra óptica com núcleo de 100\'mü\'m. A cavidade projetada e implementada, produz um feixe com comprimento de onda de 532nm (laser verde), largura de banda de 0,5nm, potência máxima em torno de 2,5W na saída da fibra óptica e pulsos com duração máxima de 3s, que são requisitos para os tratamentos oftalmológicos associados a este tipo de equipamento. É importante destacar que a cavidade foi projetada e desenvolvida inteiramente com tecnologia nacional, sendo o primeiro trabalho desenvolvido no Brasil, que se tornou efetivamente um equipamento final para uso clínico. Além do projeto da cavidade laser, são descritos neste trabalho os sistemas mecânico e eletrônico, que possibilitaram seu funcionamento na integração do fotocoagulador. O fotocoagulador foi testado em pacientes voluntários da Escola Paulista de Medicina da UNIFESP, apresentando resultados comparáveis aos sistemas importados. / This work presents the research and the development of a solid state laser cavity with second harmonic generation for ophthalmological purpose. The laser cavity is part of a major project intended to produce a handle photocoagulator. This medical equipment is applied in several clinical protocols related to retinal and anterior chamber pathologies, such as diabetic retinopathy, retinopathy of prematurity, glaucoma, macular edema and retinal detachment. The present cavity is composed by three mirrors disposed in a V shape architecture. One laser diode pumps the Nd:YAG crystal to generate the 1064nm laser that is converted by second harmonic generation in 532nm through the KTP crystal (green laser). The coupling system attached in the cavity is able to collimate until 90% of the laser beam inside a optical fiber with 100 \'mü\'m core. The developed cavity produces a beam with wavelength of 532nm, spectral width of 0.5nm, maximum power around 2.5W in the end of the optical fiber and maximum pulse duration of 3s. Those parameters are requirements for ophthalmological treatments related to this kind of equipment. It is important to declare that the cavity was projected and developed in Brazil. This is the first work in this country that becomes effectively a device to clinical application. Besides the cavity design project, in this work also describes the mechanical and electronic sub systems that was responsible to the laser control and photocoagulator assembler. This product was tested in patients eyes from UNIFESP (Escola Paulista de Medicina), and showed similar results compared to the systems on the market.

La nanophotonique non-linéaire offre une opportunité unique pour ouvrir de nouvelles voies vers des applications dans les détecteurs, les ordinateurs et la cryptographie quantique. Cependant, la faiblesse intrinsèque de la réponse non-linéaire des milieux de taille inférieure au micromètres limite fortement l’efficacité des sources optique à cette échelle. Combiner l'exaltation du champ électromagnétique dans les métaux (appelée résonance plasmonique) et l'efficacité non-linéaire de nanocristaux non-centosymétriques apparait extrêmement souhaitable et constitue le cœur de ce projet. Dans ce cadre, le travail présenté dans cette thèse consiste en une approche numérique quantitative des processus linéaires et non-linéaires (génération de second harmonique et de paires de photons) mis en jeu dans les nanostructures hybrides afin de pouvoir « accorder » les résonances plasmoniques et optimiser le couplage lumière-matière. L’étude menée prédit une exaltation par plusieurs ordres de grandeur des processus non linéaires modélisés au sein de particules composites. / Nonlinear nanophotonics offers a unique opportunity to open new path toward a wide range of pratical applications in sensors, quantum computers, cryptography devices. The main challenge is to enhance nonlinear response of nanosized particles in order to integrate them in optical components. On this purpose, we want to combine the electromagnetic field enhancement in metals (due to a phenomenon called plasmonic resonances) with non linear efficiency of non centrosymmetric nanocrystals.In this thesis, we present a numerical approach for simulating linear and non linear optical processes (second harmonic generation and spontaneous numerical down conversion) in hybrid nanostructures in order to “ tune “ plasmonic resonances and optimize light/matter coupling. The study predicts an enhancement by several orders of magnitude of the non linear phenomena modeled in composite nano particles.

O presente trabalho trata-se do desenvolvimento de uma cavidade Laser de estado sólido e geração de segundo harmônico, para fins oftalmológicos. A cavidade faz parte de um projeto maior que se refere a um fotocoagulador portátil, utilizado em diversos protocolos clínicos relacionados às doenças da retina e câmara anterior, como retinopatia diabética, retinopatia da prematuridade, glaucoma, edema macular e descolamento de retina. A cavidade proposta é composta por três espelhos dispostos em uma arquitetura em V. Um laser de diodo bombeia um cristal de Nd:YAG para a geração de laser em 1064nm que passa por um cristal de KTP para a geração de segundo harmônico em 532nm (laser verde). O sistema de acoplamento indexado à cavidade acopla até 90% da potência de saída em uma fibra óptica com núcleo de 100\'mü\'m. A cavidade projetada e implementada, produz um feixe com comprimento de onda de 532nm (laser verde), largura de banda de 0,5nm, potência máxima em torno de 2,5W na saída da fibra óptica e pulsos com duração máxima de 3s, que são requisitos para os tratamentos oftalmológicos associados a este tipo de equipamento. É importante destacar que a cavidade foi projetada e desenvolvida inteiramente com tecnologia nacional, sendo o primeiro trabalho desenvolvido no Brasil, que se tornou efetivamente um equipamento final para uso clínico. Além do projeto da cavidade laser, são descritos neste trabalho os sistemas mecânico e eletrônico, que possibilitaram seu funcionamento na integração do fotocoagulador. O fotocoagulador foi testado em pacientes voluntários da Escola Paulista de Medicina da UNIFESP, apresentando resultados comparáveis aos sistemas importados. / This work presents the research and the development of a solid state laser cavity with second harmonic generation for ophthalmological purpose. The laser cavity is part of a major project intended to produce a handle photocoagulator. This medical equipment is applied in several clinical protocols related to retinal and anterior chamber pathologies, such as diabetic retinopathy, retinopathy of prematurity, glaucoma, macular edema and retinal detachment. The present cavity is composed by three mirrors disposed in a V shape architecture. One laser diode pumps the Nd:YAG crystal to generate the 1064nm laser that is converted by second harmonic generation in 532nm through the KTP crystal (green laser). The coupling system attached in the cavity is able to collimate until 90% of the laser beam inside a optical fiber with 100 \'mü\'m core. The developed cavity produces a beam with wavelength of 532nm, spectral width of 0.5nm, maximum power around 2.5W in the end of the optical fiber and maximum pulse duration of 3s. Those parameters are requirements for ophthalmological treatments related to this kind of equipment. It is important to declare that the cavity was projected and developed in Brazil. This is the first work in this country that becomes effectively a device to clinical application. Besides the cavity design project, in this work also describes the mechanical and electronic sub systems that was responsible to the laser control and photocoagulator assembler. This product was tested in patients eyes from UNIFESP (Escola Paulista de Medicina), and showed similar results compared to the systems on the market.

In this thesis, we demonstrate, theoretically, that, by depositing a regular fused-silica fiber with optical nonlinear molecules, strong and thermodynamically stable SHG can be obtained. Our experiments also provide strong evidence for the theory. Start from the basic Maxwell equation, we derive the SHG efficiency that the excited power translates into the SHG signal. According to the SHG efficiency equation, a small radius and a long length will help to result in a high SHG efficiency, which also increases with the excited power. We fabricate silica fiber tapers with radius less than 5 μm through either wet etching or heating while stretching. Through improving the stretching setup, and adroitly manipulating both the stretching rate and the heating temperature, we are able to control the taper loss less than 1 dB. Then we dip taper part into cationic solution and anionic solution alternatively to have ISAM/CHISAM film on it. By improving the surface quality of film around a silica fiber taper, we are able to control film loss of PAH/PR film to less than 2 dB for 5 bilayers. We set up a SHG measurement stage for a nonlinear fiber, and develop a measurement method during the experiments. We have shown that by depositing (PAH/PB)10 films around a fiber taper with a diameter around 5 µm, we can obtain high SHG signal. The ratio of the obtained SHG signal to the excitation power for such a nonlinear fiber is more than 10 times of that of a 125 µm single mode fiber with the same length. Our experiment result provides strong evidence that centrosymmetric material can be used as SHG material. / Master of Science

No description available.

The main issue of this master thesis is investigation of new compounds of aminopyrazine and 3-amino-1,2,4-triazine in consideration of their potential usage in the field of nonlinear optics. The focus of this thesis was finishing of characterisation of an adduct of aminopyrazine and boric acid prepared as a part of previous bachelor thesis, as well as preparation of salts and cocrystals combining 3-amino-1,2,4-triazine with selected acids. Prepared materials were characterised mainly by the means of vibrational spectroscopy and x-ray diffraction analysis. Prediction of nonlinear optical properties of selected molecules and interpretation of recorded vibrational spectra was based on quantum chemical calculations. Finally, measurements of second harmonic generation efficiency of selected powder samples were performed.

Collagen is an important structural protein in living organisms and plays an indispensable role in connecting cells and tissues, such as in musculature, bone, and ligament. The stability and conformation of collagen are, however, strongly influenced by ambient temperature and constitutes an interesting subject of study. Thermally induced conformation change of collagen has been investigated by techniques such as differential scanning calorimetry (DSC) and second harmonic generation. DSC is a powerful method in uncovered important thermal dynamics properties including phase change, enthalpy, and thermal stability of the collagen. However, due to its collective nature, no localized information can be found. For comparison, second harmonic generation, which reflects structural symmetry, can be combined with laser scanning microscopy to investigate localized variation. It has been shown in previous studies that the thermal stability of collagen is strongly influenced by the water content within collagen. For comparison, we are investigating the conformational change of collagen under a vacuum stat with second harmonic microscopy so as to isolate environmental effects, particularly those from water and oxygen. In this way, we have found the conformational change of collagen takes place at a much higher temperature and activation energy. Additionally, the high spatial resolution achieved also allows many further possibilities.

Application of the nonlinear optical microscopy (NLOM) for investigation of biological samples has, to date, primarily focused upon the qualitative analysis of images. The general consensus is that the nonlinear optical (NLO) techniques provide enough bio- chemical information when compared to, for example, visible light microscopy. Herein, it is presented a detailed study where a set of tools for quantitative extraction of infor- mation from NLO images were developed and tested for the analysis of complex tissue assemblies. Two-photon excited autofluorescence (TPEF), second-harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS) were used for the charac- terization of atherosclerotic plaques. Our NLO-based image analysis of animal arteries affected by atherosclerotic plaque accumulation revealed that images of the healthy regions of the artery can be readily distinguished by marked differences in morphology, due to a fluorescent signal generated from the presence of generally intact elastic layer. Regions affected by lesions were dominated by lipid-rich cells and collagen fibers; the elastic layer was disrupted and the presence of fluorescent particles were also detected. Next, the potential of using information extracted from NLO images lead us to the development of a new optical index for plaque burden (OIPB). Through the OIPB, it was possible to investigate and to classify the plaque severity regarding the already established and currently used definition during clinical analyses. Extrapolating to and anticipating future applications, several methods for extracting specific information from images acquired by each NLOM modality were developed and tested. Texture analysis, particle-specific features, fractal analysis and directionality of components within the images were successfully adapted and tailored to better extract relevant information from the NLO images. Even though the methods presented in this thesis were mostly tested in images from arterial plaques, there is strong evidence that all tools presented here are capable of tracking changes that occur in many medical conditions and applications.

As queimaduras causam alterações na estrutura anatômica da pele associadas a trauma. As queimaduras podem ser classificadas em lesões de primeiro, segundo e terceiro grau. As queimaduras de terceiro grau têm sido grande foco de pesquisas em busca de tratamentos mais conservadores e de maior rapidez no reparo para um resultado funcional e estético satisfatório. O tratamento convencional consiste no uso de medicamentos tópicos e no enxerto de pele natural ou sintética. Alternativamente, a terapia laser utiliza o processo de ablação para remoção do tecido queimado necrosado, devido ao não contato mecânico, à rapidez na aplicação e alcance a áreas de difícil acesso. Deste modo, a proposta deste estudo é avaliar a viabilidade de utilizar lasers de femtossegundos de altíssima intensidade como coadjuvante no tratamento de pacientes queimados. Para o estudo, foram utilizados 25 ratos da raça Wistar, divididos em grupos de 5 animais: grupos pele sadia, pele queimada, dois tipos de tratamento (desbridamento cirúrgico ou ablação a laser de femtossegundos) e em quatro tempos de acompanhamento do processo cicatricial. Três regiões do dorso dos animais foram expostas a fonte de vapor causando queimadura de terceiro grau. No terceiro dia após a queimadura, uma das regiões foi ablacionada com laser de altíssima intensidade de pulsos ultracurtos ( λ = 785nm, 90 fs, 2 kHz e 10 μJ/pulso); outra recebeu o desbridamento cirúrgico; e a última foi considerada o controle de queimadura. As regiões foram analisados por tomografia por coerência óptica (OCT), histologia, reflectância total atenuada por espectroscopia no infravermelho usando transformada de Fourier (μATR-FTIR), microscopia de fluorescência por excitação de dois fótons (TPEFM) e a técnica de geração de segundo harmônico (SHG), nos dias 3, 5, 7 e 14 após os tratamentos. Os resultados mostraram que nas condições de irradiação utilizadas foi possível obter remoção de debris de queimadura de terceiro grau. As técnicas utilizadas para caracterização do tecido permitiram verificar que em todos os tratamentos houve a promoção da reparação tecidual. No décimo quarto dia, a curva de regeneração mostrou que o coeficiente de atenuação do tecido ablacionado a laser converge para os valores da pele sadia, porém as fibras de colágeno ainda não atingiram a mesma organização das fibras presentes na pele sadia. / Burns cause changes in the anatomical structure of the skin associated with trauma. The severity of the burn injury is divided into first, second and third-degree burns. The third-degree burns have been a major focus of research in search of more conservative treatments and faster results in repair for a functional and cosmetically acceptable. The conventional treatment is the use of topical natural or synthetic skin graft. An alternative therapy is the laser ablation process for burned tissue necrosis removal due to the no mechanical contact, fast application and access to difficult areas. The purpose of this study is to evaluate the feasibility of using high intensity femtosecond lasers as an adjunct treatment of burned patients. For this study, 65 Wistar rats were divided into groups of five animals: healthy skin, burned skin, two types of treatment (surgical debridement or femtosecond laser ablation) and four different times in the healing process monitoring. Three regions of the back of the animals were exposed to steam source causing third-degree burn. On the third day after the burn, one of the regions was ablated with high intensity ultrashort laser pulses (λ = 785 nm, 90 fs, 2 kHz and 10 μJ/ pulse), the other received surgical debridement, and the last was considered the burn control. The regions were analyzed by optical coherence tomography (OCT), histology, attenuated total reflectance infrared spectroscopy using Fourier transform (μ-ATR-FTIR), two-photon excitation fluorescence microscopy (TPEFM) and second harmonic generation technique (SHG) on days 3, 5, 7 and 14 pos-treatments. The results showed that with the laser irradiation conditions used it was possible to remove debris from third degree burn. The techniques used to characterize the tissue allowed to verify that all treatments promoted wound healing. On the fourteenth day, the regeneration curve showed that the attenuation coefficient of laser ablated tissue converges to the values of healthy skin, but collagen fibers have not yet reached the same organization of those in the healthy skin

As queimaduras causam alterações na estrutura anatômica da pele associadas a trauma. As queimaduras podem ser classificadas em lesões de primeiro, segundo e terceiro grau. As queimaduras de terceiro grau têm sido grande foco de pesquisas em busca de tratamentos mais conservadores e de maior rapidez no reparo para um resultado funcional e estético satisfatório. O tratamento convencional consiste no uso de medicamentos tópicos e no enxerto de pele natural ou sintética. Alternativamente, a terapia laser utiliza o processo de ablação para remoção do tecido queimado necrosado, devido ao não contato mecânico, à rapidez na aplicação e alcance a áreas de difícil acesso. Deste modo, a proposta deste estudo é avaliar a viabilidade de utilizar lasers de femtossegundos de altíssima intensidade como coadjuvante no tratamento de pacientes queimados. Para o estudo, foram utilizados 25 ratos da raça Wistar, divididos em grupos de 5 animais: grupos pele sadia, pele queimada, dois tipos de tratamento (desbridamento cirúrgico ou ablação a laser de femtossegundos) e em quatro tempos de acompanhamento do processo cicatricial. Três regiões do dorso dos animais foram expostas a fonte de vapor causando queimadura de terceiro grau. No terceiro dia após a queimadura, uma das regiões foi ablacionada com laser de altíssima intensidade de pulsos ultracurtos ( λ = 785nm, 90 fs, 2 kHz e 10 μJ/pulso); outra recebeu o desbridamento cirúrgico; e a última foi considerada o controle de queimadura. As regiões foram analisados por tomografia por coerência óptica (OCT), histologia, reflectância total atenuada por espectroscopia no infravermelho usando transformada de Fourier (μATR-FTIR), microscopia de fluorescência por excitação de dois fótons (TPEFM) e a técnica de geração de segundo harmônico (SHG), nos dias 3, 5, 7 e 14 após os tratamentos. Os resultados mostraram que nas condições de irradiação utilizadas foi possível obter remoção de debris de queimadura de terceiro grau. As técnicas utilizadas para caracterização do tecido permitiram verificar que em todos os tratamentos houve a promoção da reparação tecidual. No décimo quarto dia, a curva de regeneração mostrou que o coeficiente de atenuação do tecido ablacionado a laser converge para os valores da pele sadia, porém as fibras de colágeno ainda não atingiram a mesma organização das fibras presentes na pele sadia. / Burns cause changes in the anatomical structure of the skin associated with trauma. The severity of the burn injury is divided into first, second and third-degree burns. The third-degree burns have been a major focus of research in search of more conservative treatments and faster results in repair for a functional and cosmetically acceptable. The conventional treatment is the use of topical natural or synthetic skin graft. An alternative therapy is the laser ablation process for burned tissue necrosis removal due to the no mechanical contact, fast application and access to difficult areas. The purpose of this study is to evaluate the feasibility of using high intensity femtosecond lasers as an adjunct treatment of burned patients. For this study, 65 Wistar rats were divided into groups of five animals: healthy skin, burned skin, two types of treatment (surgical debridement or femtosecond laser ablation) and four different times in the healing process monitoring. Three regions of the back of the animals were exposed to steam source causing third-degree burn. On the third day after the burn, one of the regions was ablated with high intensity ultrashort laser pulses (λ = 785 nm, 90 fs, 2 kHz and 10 μJ/ pulse), the other received surgical debridement, and the last was considered the burn control. The regions were analyzed by optical coherence tomography (OCT), histology, attenuated total reflectance infrared spectroscopy using Fourier transform (μ-ATR-FTIR), two-photon excitation fluorescence microscopy (TPEFM) and second harmonic generation technique (SHG) on days 3, 5, 7 and 14 pos-treatments. The results showed that with the laser irradiation conditions used it was possible to remove debris from third degree burn. The techniques used to characterize the tissue allowed to verify that all treatments promoted wound healing. On the fourteenth day, the regeneration curve showed that the attenuation coefficient of laser ablated tissue converges to the values of healthy skin, but collagen fibers have not yet reached the same organization of those in the healthy skin