O Câncer nas últimas décadas tem se tornado um evidente problema de saúde pública mundial. Os números de novos casos que surgem a cada ano e as altas taxas de mortalidade levam os pesquisadores a procurar formas de conter o avanço dessa doença. A principal forma de tratamento e que possui a maior incidência de cura é o uso de quimioterápicos, que são substâncias químicas utilizadas isoladas ou em combinação, com o objetivo de tratar as neoplasias malignas. Entretanto eles atuam sem especificidade, não destruindo seletivamente e exclusivamente as células tumorais o que causa graves efeitos colaterais aos pacientes. Com o intuito de aumentar a seletividade do tratamento, diminuir a toxicidade e aumentar o poder de cura o presente trabalho utiliza duas abordagens para o combate do câncer, a nanotecnologia (uso de sistemas de liberação de fármacos) e a hipertermia. Foram preparadas, caracterizadas e avaliadas quanto à atividade antitumoral in vitro nanocápsulas contendo o agente quimioterápico selol (composto semi-sintético provindo do óleo de girassol e que possui selênio na sua estrutura) e fluído magnético iônico (composto por nanopartículas magnéticas de maghemita, ?-Fe2O3. Ao total foram preparadas quatro diferentes formulações pelo método de nanoprecipitação descrito por Fessi com algumas modificações. As nanocápsulas apresentaram um tamanho de partícula máximo de 230,5 nm (± 4,5), com índice de polidispersividade < 0,267 (± 0,05) e potencial zeta que variou de -54,4 mV (± 3,4) a -28,6 mV (± 4,3). Foram realizadas análises da morfologia das nanocápsulas através de microscopia eletrônica de transmissão que confirmaram o tamanho nanométrico do sistema preparado. Todas as formulações demonstraram ser estáveis durante o tempo 3 meses quando armazenadas a temperatura de 4oC. Nos estudos celulares foram utilizadas as linhagens B16- F10 (melanoma murino) e OSCC (carcinoma epidermóide de boca humano), sendo que as mesmas mostraram diferentes comportamentos quando incubadas com as formulações em diferentes concentrações. Na linhagem B16-F10 foi observado um maior efeito de morte causado pelo selol (a viabilidade celular chegou a 52,5 % ± 8,4), já quando o campo magnético foi utilizado não foi possível observar um aumento da morte celular. No estudos com a linhagem OSCC, a mesma demonstrou resistência quando foi tratada com selol e na ausência de campo magnético, já quando o campo magnético foi utilizado a viabilidade celular chegou a 33,3% (± 0,3), indicando um forte efeito hipertêmico nesta linhagem. Mais estudos devem ser realizados para entendermos o efeito do sistema preparado perante diferentes linhagens celulares, no entanto podemos confirmar o sucesso no preparo do mesmo e a capacidade de causar morte de diferentes células neoplásicas, o que indica uma importante arma para atuar futuramente no combate do câncer. / In the latest decades, cancer has become a clear public health problem worldwide. The neoplastic diseases increase each year and high mortality rates lead researchers to develop new approaches able to contain the progress of this disease. The main treatment type which has the highest incidence of cure is based on chemotherapeutic agents used alone or in combination. However, they act without specificity and selectively destroying both tumor and normal cells causing serious side effects to patients. In order to enhance the selectivity of the treatment decreasing toxicity and increase the healing power, the present study employs two approaches to treat the cancer, nanotechnology (the use of drug delivery systems) and hyperthermia (magnetic fluid). Nanocapsules containing the chemotherapeutic agent selol (semi-synthetic compound coming from sunflower oil and that has selenium in its structure) and maghemite magnetic nanoparticles (?-Fe2O3) were prepared, characterized, and evaluated in respect with their in vitro antitumor activity. Four different formulations were prepared by the nanoprecipitation method described by Fessi et al. with some modifications. The nanocapsules presented a particle size up to 230.5 nm (±4.5) with polydispersity index of 0.267 (±0.05), and zeta potential ranged from - 54.4 mV (±3.4) to - 28.6 mV (±4.3). The transmission electron microscopy analysis of nanocapsules confirmed the nanometric size system prepared. All formulations proved to be stable during 3 months as stored at 4°C. The cell lines studied were B16-F10 (murine melanoma) and OSCC (oral squamous cell carcinoma). These cell lines showed different behavior after incubation at different formulation concentrations. For cytotoxicty study on B16-F10 cells, it was observed a strong effect caused by Selol (cell viability reached 52.5% ±8.4). On the other hand, there was no cytotoxic effect on B16-F10 cells (p > 0.05) under magnetic field application. OSCC cell line showed a resistance to treatment with selol and in the absence of AC magnetic field. However, after magnetic field activation the cell viability reached 33.3% (±0.3) indicating a strong hyperthermic effect on OSCC cells. Therefore, it has been confirmed nanocapsules containing selol and magnetic fluid are able to destroy B16-F10 or OSCC neoplastic cells indicating an important weapon for future work in the treatment against cancer.

Magnetic fluid flow by thermomagnetic convection with and without buoyancy was studied in experiments and computational simulations. A mineral oil based ferro magnetic fluid was subjected to varying magnetic fields to induce thermomagnetic convection. As such fluids are mainly developed to increase heat transfer for cooling the fundamental effects on magnetic fluid flow was investigated using various magnetic field distributions. Computational simulations of natural and thermomagnetic convection are based on a Finite-Element technique and considered a constant magnetic field gradient, a realistic magnetic field generated by a permanent magnet and alternating magnetic fields. The magnetic field within the fluid domain was calculated by the magneto-static Maxwell equations and considered in an additional magnetic body force known as the Kelvin body force by numerical simulations. The computational model coupled the solutions of the magnetic field equations with the heat and fluid flow equations. Experiments to investigate thermomagnetic convection in the presence of terrestrial gravity used infrared thermography to record temperature fields that are validated by a corresponding numerical analysis. All configurations were chosen to investigate the response of the magnetic fluid to the applied body forces and their competition by varying the magnetic field intensity and its spatial distribution. As both body forces are temperature dependent, situations were analysed numerically and experimentally to give an indication of the degree by which heat transfer may be enhanced or reduced. Results demonstrate that the Kelvin body force can be much stronger than buoyancy and can induce convection where buoyancy is not able to. This was evident in a transition area if parts of a fluid domain are not fully magnetically saturated. Results for the transition from natural convection to thermomagnetic convection suggest that the domain of influence of the Kelvin body force is aligned with the dominance of the respective body force. To characterise the transition a body force ratio of the Kelvin body force to buoyancy was developed that identified the respective driving forces of the convection cells. The effects on heat transfer was quantified by the Nusselt number and a suitable Rayleigh number. A modified Rayleigh number was used when both body forces were active to define an effective body force by taking the relative orientation of both forces into account. Results for the alternating magnetic field presented flow fields that altered with the frequency of the applied magnetic field but with varying amplitude. This affected the heat transfer that alternated with the frequency but failed to respond instantaneously and a phase lag was observed which was characterised by three different time scales.

Adaptive optics (AO) systems make use of active optical elements, namely wavefront correctors, to improve the resolution of imaging systems by compensating for complex optical aberrations. Recently, magnetic fluid deformable mirrors (MFDM) were proposed as a novel type of wavefront correctors that offer cost and performance advantages over existing wavefront correctors. These mirrors are developed by coating the free surface of a magnetic fluid with a thin reflective film of nano-particles. The reflective surface of the mirrors can be deformed using a locally applied magnetic field and thus serves as a wavefront corrector. MFDMs have been found particularly suitable for ophthalmic imaging systems where they can be used to compensate for the complex aberrations in the eye that blur the images of the internal parts of the eye. However, their practical implementation in clinical devices is hampered by the lack of effective methods to control the shape of their deformable surface. The research work reported in this thesis presents solutions to the surface shape control problem in a MFDM that will make it possible for such devices to become integral components of retinal imaging AO systems. The first major contribution of this research is the development of an accurate analytical model of the dynamics of the mirror surface shape. The model is developed by analytically solving the coupled system of fluid-magnetic equations that govern the dynamics of the surface shape. The model is presented in state-space form and can be readily used in the development of surface shape control algorithms. The second major contribution of the research work is a novel, innovative design of the MFDM. The design change was prompted by the findings of the analytical work undertaken to develop the model mentioned above and is aimed at linearizing the response of the mirror surface. The proposed design also allows for mirror surface deflections that are many times higher than those provided by the conventional MFDM designs. A third contribution of this thesis involves the development of control algorithms that allowed the first ever use of a MFDM in a closed-loop adaptive optics system. A decentralized proportional-integral (PI) control algorithm developed based on the DC model of the wavefront corrector is presented to deal mostly with static or slowly time-varying aberrations. To improve the stability robustness of the closed-loop AO system, a decentralized robust proportional-integral-derivative (PID) controller is developed using the linear-matrix-inequalities (LMI) approach. To compensate for more complex dynamic aberrations, an Hinf controller is designed using the mixed-sensitivity Hinf design method. The proposed model, design and control algorithms are experimentally tested and validated.

Adaptive optics (AO) systems make use of active optical elements, namely wavefront correctors, to improve the resolution of imaging systems by compensating for complex optical aberrations. Recently, magnetic fluid deformable mirrors (MFDM) were proposed as a novel type of wavefront correctors that offer cost and performance advantages over existing wavefront correctors. These mirrors are developed by coating the free surface of a magnetic fluid with a thin reflective film of nano-particles. The reflective surface of the mirrors can be deformed using a locally applied magnetic field and thus serves as a wavefront corrector. MFDMs have been found particularly suitable for ophthalmic imaging systems where they can be used to compensate for the complex aberrations in the eye that blur the images of the internal parts of the eye. However, their practical implementation in clinical devices is hampered by the lack of effective methods to control the shape of their deformable surface. The research work reported in this thesis presents solutions to the surface shape control problem in a MFDM that will make it possible for such devices to become integral components of retinal imaging AO systems. The first major contribution of this research is the development of an accurate analytical model of the dynamics of the mirror surface shape. The model is developed by analytically solving the coupled system of fluid-magnetic equations that govern the dynamics of the surface shape. The model is presented in state-space form and can be readily used in the development of surface shape control algorithms. The second major contribution of the research work is a novel, innovative design of the MFDM. The design change was prompted by the findings of the analytical work undertaken to develop the model mentioned above and is aimed at linearizing the response of the mirror surface. The proposed design also allows for mirror surface deflections that are many times higher than those provided by the conventional MFDM designs. A third contribution of this thesis involves the development of control algorithms that allowed the first ever use of a MFDM in a closed-loop adaptive optics system. A decentralized proportional-integral (PI) control algorithm developed based on the DC model of the wavefront corrector is presented to deal mostly with static or slowly time-varying aberrations. To improve the stability robustness of the closed-loop AO system, a decentralized robust proportional-integral-derivative (PID) controller is developed using the linear-matrix-inequalities (LMI) approach. To compensate for more complex dynamic aberrations, an Hinf controller is designed using the mixed-sensitivity Hinf design method. The proposed model, design and control algorithms are experimentally tested and validated.

Ce travail explore expérimentalement en géométrie microfluidique, des instabilités sous champ de fluides magnétiques aqueux, aux propriétés bien caractérisées et dont les nanoparticules sont stabilisées électrostatiquement.La micro-convexion magnétique observée à l'interface miscible entre le fluide magnétique et l'eau est étudiée quantitativement dans une cellule de Hele-Shaw sous champ magnétique homogène, en particulier par vélocimétrie par image de particules. Les résultats sont comparés aux prédictions théoriques et à des simulations numériques. Au delà de la caractérisation des champs critiques, il est observé qu'une augmentation du champ H accélère la croissance des doigts, comme H2, tandis que la figure de digitation n'est pas modifiée. Une application au mélange en microfluidique est ici envisagée. L'étude de la micro-convexion a révélé une diffusion effective de coefficient beaucoup plus grand que celui des nanoparticules, tel que prédit par la formule de Stockes-Einstein ou obtenu par des mesures directes. Des explorations expérimentales montrent que cette diffusion effective provient d'un écoulement lié à la différence de densité des deux fluides. La diffusion semble influencée par les agents qui stabilisent les nanoparticules. Des gouttes de liquide magnétique concentré co-existant avec une phase diluée sont obtenues par séparation de phase induite par ajout de sel et/ou application d'un champ magnétique. Leur déformation sous champ permet de suivre l'évolution temporelle de la phase concentrée métastable. Dans un champ magnétique précessant à l'angle magique, les gouttes se comportent comme en champ tournant, sauf en ce qui concerne leur déformation initiale. / Magnetic field induced instabilities of magnetic fluids in microfluidic environment are investigated experimentally. Electrically stabilized water-based magnetic nanocolloids are used and throughout characterized.Magnetic micro-convection, observed at a miscible magnetic fluid-water interface in a Hele-Shaw cell in homogeneous field, is studied quantitatively and compared with theoretical predictions and numerical simulations, micro-convective flows being characterized by particle image velocimetry. Besides the critical field determination, it is shown that an increase of the magnetic field H speeds up the finger growth, which scales as H2, while the size of the fingering pattern is not changed. An application towards mixing enhancement in microfluidics is considered.The micro-convection study reveals a much larger effective diffusion coefficient of the nanoparticles than expected from Stokes - Einstein relation and standard determinations. Investigations with the same setup and with continuous microfluidics show that the effective diffusion mostly arises from a flow induced by the density difference between the miscible fluids. Additionally, the diffusion coefficient seems to be influenced by the particle stabilizing agents.Drops of a concentrated magnetic phase in co-existence with a dilute one are formed by phase separation after salt addition to the magnetic fluid and/or the application of a magnetic field. Their under-field shape deformations allow investigating the time evolution of the concentrated phase. Experiments show that in a precessing field at magic angle, the drops behave as in a rotating field except the initial shape deformation before quick elongation.

Made available in DSpace on 2014-07-29T15:12:48Z (GMT). No. of bitstreams: 1 Dissertacao - Wesley Renato Viali.pdf: 3929545 bytes, checksum: b4e900de56f7f751a05beaeb0b326f0b (MD5) Previous issue date: 2009-03-18 / In this work maghemite nanoparticles were synthesized by co-precipitating Fe2+ and Fe3+ in alkaline medium. The freshly prepared magnetite was oxidized by two different routes: by bubbling O2 through an acid suspension of magnetite nanoparticles or by hydrothermal treatment of magnetite with ferric nitrate/nitric acid solution. After oxidation, the nanoparticles were covered with oleic acid and the grafting coefficient was evaluated according to the oxidation method and pH employed in the adsorption experiments. The covered particles were dispersed in mineral and vegetable insulating oils, resulting in magnetic fluids whose colloidal stability was investigated in regard to the following parameters: dilution, heating, water content, chemical composition of insulating oils and addition of oleic acid. The nanoparticles were characterized by X-ray diffratometry, thermogravimetric and differential thermal analyses and infrared spectroscopy. The Fe3+/Fe2+ molar ratio in the solids was determined by UV-Vis spectrometry. The magnetic fluids were characterized regarding the volume fraction of nanoparticles, the water content, and their colloidal stability was monitored by dynamic light scattering measurements and visual observations. The results obtained from the analyses indicated that the oxidized magnetite nanoparticles (5 to 10 nm) have inverse spinel structure and Fe3+/Fe2+ molar ratio varied from 20 to 70, depending on the oxidation method and employed conditions. The grafting coefficient varied from 2,1 to 4,8, reflecting the oleic acid adsorption conditions, and the further treatments. It was also observed that by controlling the experimental conditions, a grafting coefficient very close to a Langmuir s monolayer can be achieved, together with a decrease in the amount of physisorbed species which contribute negatively to the colloidal stability. The study of colloidal stability showed that dilution, heating and XVII water content have a great influence in the sedimentation of diluted magnetic fluids, when they are diluted with minerals insulating oils. It was verified that the magnetic fluids diluted with vegetable insulating oil showed very high colloidal stability in the accelerated thermal aging experiment / Neste trabalho foram preparadas nanopartículas de maghemita pelo método da coprecipitação de íons Fe3+ e Fe2+ em meio básico. A magnetita inicialmente obtida foi oxidada utilizando-se gás oxigênio ou solução de nitrato férrico/ácido nítrico. Após a oxidação, as nanopartículas foram revestidas com ácido oleico e a eficiência deste processo foi avaliada em função do método de oxidação e do pH de adsorção. As partículas revestidas foram dispersas em óleos isolantes dos tipos naftênico, parafínico ou vegetal, resultando em fluidos magnéticos cujas estabilidades coloidais foram avaliadas em função dos seguintes parâmetros: diluição, aquecimento, teor de água, natureza do meio dispersante e adição de ácido oleico. As nanopartículas foram caracterizadas por difratometria de raios X, análise termogravimétrica e térmica diferencial e espectroscopia de infravermelho. A razão Fe3+/Fe2+ nos sólidos foi determinada por espectrofotometria no visível. Os fluidos magnéticos foram caracterizados quanto à fração volumétrica de nanopartículas e ao teor de água, e sua estabilidade coloidal foi acompanhada por espalhamento dinâmico de luz e por medidas visuais de turbidez. Os resultados das análises e experimentos indicaram que as nanopartículas de magnetita oxidada (5 a 10 nm) apresentaram estrutura espinélio inverso e razão Fe3+/Fe2+ desde 20 até 70, dependendo do método e condições de oxidação empregadas. O coeficiente de revestimento variou de 2,1 a 4,8, refletindo tanto as condições utilizadas nos procedimentos de adsorção do ácido oleico, como também os tratamentos subseqüentes. Demonstrou-se que através do controle das condições experimentais pode-se obter um revestimento muito próximo ao de uma monocamada de Langmuir, bem como reduzir a quantidade de XV espécies moleculares fisissorvidas que contribuem negativamente para a estabilidade coloidal. O estudo da estabilidade coloidal mostrou que a diluição, o aquecimento e o teor de água favorecem a sedimentação dos fluidos magnéticos quando estes são diluídos em óleos isolantes naftênico e parafínico. Verificou-se que os fluidos magnéticos em óleo vegetal quando em frações volumétricas baixas apresentaram alta estabilidade coloidal em experimentos de envelhecimento acelerado

O principal interesse neste estudo foi a proposição de uma nova classe de material que permite a ação combinada da Terapia Fotodinâmica (TFD) e da Hipertermia (HPT), projetadas para trabalhar sinergicamente, que possa levar a uma considerável regressão de tumores neoplásicos após mínimas doses de dissipação de calor e/ou fotossensitização luminosa. Esta nova classe de material se baseia em um lipossoma de longo tempo de circulação associado ao fármaco fotossensibilizador (FS) zinco ftalocianina (ZnPC), na presença de fluido magnético (FM) constituído por nanopartículas de ferrita de cobalto (CoFe2O4) recobertas com ácido cítrico. As propriedades fotofísicas (em meio orgânico e em meio lipossomal) e os estudos fotobiológicos em células da linhagem B-16 foram desenvolvidos para avaliar as propriedades da ZnPC na ausência e na presença de FM. As propriedades fotofísicas da ZnPC em meio orgânico e lipossomal, na ausência e na presença de FM, foram realizadas empregando-se técnicas de espectroscopia no estado estacionário e resolvido no tempo. Foi possível determinar importantes parâmetros que elucidaram o potencial fotodinâmico da partícula mista ZnPC/FM com um apropriado sistema de liberação, confirmando sua viabilidade para aplicação em estudos in vitro e in vivo. A interação de fluidos magnéticos biocompatíveis (FMBs) com a macromolécula biológica, a soro albumina bovina (BSA), foi estudada por meio da determinação da constante de ligação (Kb) e do número de sítios de ligação (n),. Este formalismo aplicado para nanopartículas magnéticas usadas em aplicações biológicas foi realizado pela primeira vez neste rabalho. As toxicidades da ZnPC, do FM e da partícula mista ZnPC/FM, em meio homogêneo e lipossomal, na ausência e na presença de luz e/ou campo magnético, foram estudadas. Na última parte deste trabalho iniciou-se o desenvolvimento de um modelo tumoral subcutâneo na região dorso-lateral de camundongos C57BL6J. Este é considerado o primeiro passo para a transferência dos resultados fotobiológicos no desenvolvimento de um tratamento clínico proposto para a terapia de humanos. Os nossos resultados demonstraram que o complexo ZnPC/FM em meio lipossomal apresenta propriedades fotofísicas e fotobiológicas úteis, ativados pela luz e campo magnético, como uma geração de fármacos atuando sinergicamente pela TFD e pela HPT. / The main goal in this study was to introduce a new material class that allows the combined action of Photodunamic therapy (PDT) and Hyperthermia therapy (HPT), designed to work in a synergetic ways, leading to an expected enhancement of the tumor damage after minimum drug doses and based on heat dissipation and /or light photosensitization. This new material class is a ?stealth? liposome associated with the photosensitizer drug zinc phthalocyanine (ZnPC), in the presence of a magnetic fluid (MF) based on nanoparticles of cobalt-ferrite (CoFe2O4) surface-coated with citric acid. Photophysical properties (in organic and liposomal medium) and photobiological studies in B-16 tumor cell lines were developed to evaluate the properties of the ZnPC in the absence and in the presence of MF. The photophysical properties of the ZnPC in organic and liposomal medium, were realize using spectroscopy techniques in the steady state and by time resolved studies. It was possible to quantify important parameters that elucidated and confirm the photodynamic potential of the ZnPC/MF complex as an appropriate drug delivery system, confirming its viability for application in vitro and in vivo studies. The interaction of the biocompatible magnetic fluids (FMBs) with the biological macromolecule, serum albumin proteins (BSA),was investigated through the determination of the binding constant (Kb) as well as the binding stoichiometry of the complex (n). This is the first time that this formalism was applicable to magnetic nanoparticles used in biological application. The toxicities of the ZnPC, the MF and also for the combined particle (the ZnPC/MF complex), in homogeneous and liposomal medium, in the absence and in the light presence and/or magnetic field were studied, and all the parameters that will allow the used of this synergic compound have been defined. In the last part of this work it was also started the establishment of one animal model by development of subcutaneous tumoral skin cancer in the back-lateral area of C57BL6J mice. This are the first step in the transfer of the photobiological results to the development of a clinical trial proposal for human therapy Our results demonstrated that the ZnPC/MF complex in liposome medium showed useful photophysical and photobiological properties, acting by light activation and AC magnetic field as a new generation of synergic drugs for TFD and cellular HPT.

O Câncer nas últimas décadas tem se tornado um evidente problema de saúde pública mundial. Os números de novos casos que surgem a cada ano e as altas taxas de mortalidade levam os pesquisadores a procurar formas de conter o avanço dessa doença. A principal forma de tratamento e que possui a maior incidência de cura é o uso de quimioterápicos, que são substâncias químicas utilizadas isoladas ou em combinação, com o objetivo de tratar as neoplasias malignas. Entretanto eles atuam sem especificidade, não destruindo seletivamente e exclusivamente as células tumorais o que causa graves efeitos colaterais aos pacientes. Com o intuito de aumentar a seletividade do tratamento, diminuir a toxicidade e aumentar o poder de cura o presente trabalho utiliza duas abordagens para o combate do câncer, a nanotecnologia (uso de sistemas de liberação de fármacos) e a hipertermia. Foram preparadas, caracterizadas e avaliadas quanto à atividade antitumoral in vitro nanocápsulas contendo o agente quimioterápico selol (composto semi-sintético provindo do óleo de girassol e que possui selênio na sua estrutura) e fluído magnético iônico (composto por nanopartículas magnéticas de maghemita, ?-Fe2O3. Ao total foram preparadas quatro diferentes formulações pelo método de nanoprecipitação descrito por Fessi com algumas modificações. As nanocápsulas apresentaram um tamanho de partícula máximo de 230,5 nm (± 4,5), com índice de polidispersividade < 0,267 (± 0,05) e potencial zeta que variou de -54,4 mV (± 3,4) a -28,6 mV (± 4,3). Foram realizadas análises da morfologia das nanocápsulas através de microscopia eletrônica de transmissão que confirmaram o tamanho nanométrico do sistema preparado. Todas as formulações demonstraram ser estáveis durante o tempo 3 meses quando armazenadas a temperatura de 4oC. Nos estudos celulares foram utilizadas as linhagens B16- F10 (melanoma murino) e OSCC (carcinoma epidermóide de boca humano), sendo que as mesmas mostraram diferentes comportamentos quando incubadas com as formulações em diferentes concentrações. Na linhagem B16-F10 foi observado um maior efeito de morte causado pelo selol (a viabilidade celular chegou a 52,5 % ± 8,4), já quando o campo magnético foi utilizado não foi possível observar um aumento da morte celular. No estudos com a linhagem OSCC, a mesma demonstrou resistência quando foi tratada com selol e na ausência de campo magnético, já quando o campo magnético foi utilizado a viabilidade celular chegou a 33,3% (± 0,3), indicando um forte efeito hipertêmico nesta linhagem. Mais estudos devem ser realizados para entendermos o efeito do sistema preparado perante diferentes linhagens celulares, no entanto podemos confirmar o sucesso no preparo do mesmo e a capacidade de causar morte de diferentes células neoplásicas, o que indica uma importante arma para atuar futuramente no combate do câncer. / In the latest decades, cancer has become a clear public health problem worldwide. The neoplastic diseases increase each year and high mortality rates lead researchers to develop new approaches able to contain the progress of this disease. The main treatment type which has the highest incidence of cure is based on chemotherapeutic agents used alone or in combination. However, they act without specificity and selectively destroying both tumor and normal cells causing serious side effects to patients. In order to enhance the selectivity of the treatment decreasing toxicity and increase the healing power, the present study employs two approaches to treat the cancer, nanotechnology (the use of drug delivery systems) and hyperthermia (magnetic fluid). Nanocapsules containing the chemotherapeutic agent selol (semi-synthetic compound coming from sunflower oil and that has selenium in its structure) and maghemite magnetic nanoparticles (?-Fe2O3) were prepared, characterized, and evaluated in respect with their in vitro antitumor activity. Four different formulations were prepared by the nanoprecipitation method described by Fessi et al. with some modifications. The nanocapsules presented a particle size up to 230.5 nm (±4.5) with polydispersity index of 0.267 (±0.05), and zeta potential ranged from - 54.4 mV (±3.4) to - 28.6 mV (±4.3). The transmission electron microscopy analysis of nanocapsules confirmed the nanometric size system prepared. All formulations proved to be stable during 3 months as stored at 4°C. The cell lines studied were B16-F10 (murine melanoma) and OSCC (oral squamous cell carcinoma). These cell lines showed different behavior after incubation at different formulation concentrations. For cytotoxicty study on B16-F10 cells, it was observed a strong effect caused by Selol (cell viability reached 52.5% ±8.4). On the other hand, there was no cytotoxic effect on B16-F10 cells (p > 0.05) under magnetic field application. OSCC cell line showed a resistance to treatment with selol and in the absence of AC magnetic field. However, after magnetic field activation the cell viability reached 33.3% (±0.3) indicating a strong hyperthermic effect on OSCC cells. Therefore, it has been confirmed nanocapsules containing selol and magnetic fluid are able to destroy B16-F10 or OSCC neoplastic cells indicating an important weapon for future work in the treatment against cancer.

Ferrofluids are stable colloidal homogeneous mixtures of nano-size single-domain ferromag¬netic particles covered by surfactant layer, and suspended in a carrier fluid compatible with the surfactant. Physical properties of ferrofluid allows one to control it externally using magnetic field without being in direct contact with it. The thesis presents a novel mechanism to pump ferrofluid based on the principle of variable reluctance, in an external magnetic field. The static and dynamic pressure behavior of ferrofluid in a switched DC magnetic field gives an insight into the variable reluctance behavior of ferrofluid. A ferrofluid pump based on the prin¬ciple of variable reluctance of ferrofluid subjected to an external magnetic field, is developed and hence the pump is named as Variable Reluctance Ferrofluid Pump (VRFP). Three configurations of VRFP are developed: • Single stage one-phase VRFP • Single stage two phase VRFP • Multi-stage VRFP A one-phase VRFP consisting of a check valve along with an electromagnet is designed. The valve is modeled and its transfer function is estimated using System Identification method. This model is then used in the simulation model of the pump. The pump is modeled based on the hydraulic-electric analogies. An electric circuit which represents the gross level equivalent of the pump is simulated and the results are compared with that of the experimental measurements. A two phase VRFP is implemented with two electromagnets on either side of the valve around the tube. Two types of magnetic actuation methods are introduced based on the switching sequences of the two electromagnets, namely Full Step Sequencing and Half Step Sequencing. Simulations and experiments were conducted for different pumping conditions. The one phase and two phase VRFPs are single stage structures. A multi-stage VRFP concept, in which the ferrofluid flow channel (tube) is looped through the electromagnets multiple times, is introduced. For the implementation purpose, a two-stage VRFP is discussed in this thesis. Simulations and experiments resulted in significant improvement in case of two-stage VRFP in the pump performance compared to that of single-stage VRFPs. The work presents a simple and novel design of a ferrofluid pump, which is capable of higher flow rates and pumping against higher back pressure compared to the ferrofluid pumps reported in literature. Keywords: Ferrofluid Pump, VRFP, Variable Reluctance, Multi Stage, Magnetic Fluid,

Nanotechnology has made it possible to create materials with unique properties. This development offers new opportunities and overcomes challenges for many thermal transport applications. Yet, it requires a more fundamental scientific understanding of nanoscale transport. This thesis emphasizes how simulation, mathematical, and numerical methods can lead to more grounded studies of nanoscale thermal transport for biological and physical applications. For instance, magnetic fluid hyperthermia (MFH), an emerging cancer treatment, is a noninvasive method to selectively destroy a tumor by heating a ferrofluid-impregnated malignant tissue with minimal damage to the surrounding healthy tissue. We model the problem by considering an idealized spherical tumor that is surrounded by healthy tissue. The dispersed magnetic nanoparticles in the tumor are excited by an AC magnetic field to generate heat. The temperature distribution during MFH is investigated through a bioheat transfer relation which indicates that the P\'eclet, Joule, and Fourier numbers are the more influential parameters that determine the heating during such a thermotherapy. Thus, we show that a fundamental parametric investigation of the heating of soft materials can provide pathways for optimal MFH design. Since ferrofluid materials themselves play a key role in heating, we examine six materials that are being considered as candidates for MFH use. These are simulated to investigate the heating of ferrofluid-loaded tumors. We show that iron-platinum, magnetite, and maghemite are viable MFH candidates since they are able to provide the desired heating of a tumor which will destroy it while keeping the surrounding healthy tissues at a relatively safe temperature. Recent advances in the synthesis and nanofabrication of electron devices have lead to diminishing feature sizes. This has in turn increased the power dissipation per unit area that is required to cool the devices, leading to a serious thermal management challenge. The phonon thermal conductivity is an important material property because of its role in thermal energy transport in semiconductors. A higher thermal conductivity material is capable of removing more heat since higher frequency phonons are able to travel through it. In this thesis, the effects of surface stress on the lattice thermal conductivity are presented for a silicon nanowire. Based on a continuum approach, a phonon dispersion relation is derived for a nanowire that is under surface stress and the phonon relaxation time is employed to subsequently determine its thermal conductivity. The surface stress is found to significantly influence the phonon dispersion and thus the Debye temperature. Consequently, the phonon thermal conductivity decreases with increasing surface stress. Different magnitudes of surface stress could arise from various material coatings and through different nanofabrication processes, effects of which are generally unclear and not considered. Our results show how such variations in surface stress can be gainfully used in phonon engineering and to manipulate the thermal conductivity of a nanomaterial. The thermal transport during thermoelectric cooling is also an important property since thermoelectric devices are compact, reliable, easy to control, use no refrigerants and require lower maintenance than do more traditional refrigeration devices. We focus on the Thomson effect that occurs when there is a current flow in the presence of a temperature gradient in the material, and investigate its influence on an intrinsic silicon nanowire cooler. The temperature dependence of the Thomson effect has a significant influence on the cooling temperature. We also consider thermal nonequilibrium between electrons and phonons over the carrier cooling length in the nanowire. The results show that a strong energy exchange between electrons and phonons lowers the cooling performance, suggesting useful strategies for thermoelectric device design. / Ph. D.