Tumores de mama podem ser categorizados pela expressão de diferentes receptores, como por exemplo o HER-2 (receptor de fator de crescimento epidérmico 2), sendo amplamente estudada a utilização do fármaco inibidor do receptor da tirosina–quinase, ditosilato de lapatinib. Nesse sentido, o trabalho está centrado no desenvolvimento farmacotécnico e caracterização físico-química de nanocápsulas multiparede revestidas com polissorbato 80 e fosfatidilcolina (LIPOID S75®), seguidas de revestimento com quitosana, contendo ditosilato de lapatinib (25μg/mL e 50μg/mL). Estudos físico-químicos da fase orgânica e das nanocápsulas contendo LIPOID S75®, em diferentes concentrações, foram desenvolvidos através de medidas de viscosidade, tensão superficial e analise de calorimetria exploratória diferencial, correlacionando com o tamanho de partícula e interação da fosfatidilcolina no sistema. A partir disso, escolheu-se a maior concentração de LIPOID S75® testada, para desenvolver as nanocápsulas multiparede complexadas com metal e fenilalanina contendo ditosilato de lapatinib (Lap25-P5-Q-Fe-Phe; Lap50-P5-Q-Fe-Phe; Lap25-P5-Q-Zn-Phe; Lap50-P5-Q-Zn-Phe). As formulações contendo fármaco apresentaram distribuição unimodal de partículas na faixa nanométrica, (111 - 172 nm) e baixo índice de polidispersão. A faixa de potencial zeta obtida (+16 - +22 mV) indicou o revestimento da partícula pela quitosana. O ditosilato de lapatinib foi quantificado por cromatografia líquida de alta eficiência (HPLC). A fase móvel do método consistiu em acetonitrila:acetato de amônio 0,02M (70:30), vazão de 1,0 mL/min com detecção em 260 nm. As suspensões contendo 25 μg/mL e 50 μg/mL de fármaco apresentaram teor entre 93% e 91%, respectivamente. A eficiência de encapsulação (EE%) foi acima de 90%. O conjunto destes estudos demonstra que nanocápsulas desenvolvidas são potenciais candidatas para ensaios biológicos in vitro. / Breast tumors may be categorized by the expression of different receptors such as HER-2 (growth factor epidermal receptor 2), The use of the inhibitor drug receptor tyrosine-kinase lapatinib ditosylate (Tyverb®, GlaxoSmithKline) has been widely studied. In this sense, the work is focused on pharmaceutics development and physicochemical characterization of multiwall nanocapsules coated with polysorbate 80 and phosphatidylcholine (Lipoid S75®), followed by coating with chitosan containing lapatinib ditosylate (25 μ/mL and 50 μg/mL). Physicochemical studies of the organic phase and nanocapsules containing Lipoid S75® at different concentrations were developed by viscosity, surface tension analysis and differential scanning calorimetry, correlated with the particle size and interaction of phosphatidylcholine in the system From this, we have chosen the highest concentration of lipoid S75® tested to develop complexed nanocapsules multiparede with metal and phenylalanine containing lapatinib ditosylate (Lap25-P5-Phe-Phe-Q; Lap50-P5-Q -Fc-Phe; Lap25-P5-O-Zn-Phe; Lap50-P5-Zn-O-Phe). Formulations containing lapatinib ditosylate showed unimodal distribution of particles in the nanometer range (111-172 nm) and low polydispersity index. The obtained zeta potential range (+16 - +22 mV) indicated by the chitosan particle coating. The lapatinib ditosylate was quantified by high-performance liquid chromatography (HPLC). The mobile phase consisted method in acetonitrile: 0.02M ammonium acetate (70:30), flow 1.0 mLmin-1 with detection at 260 nm. The suspensions containing 25 ugmL-1 and 50 ugmL-1 showed drug content of between 93% and 91%, respectively. The encapsulation efficiency (EE%) was above 90%. Together these studies demonstrate that the nanocapsules are potential candidates for in vitro biological assays.

Esta tese apresenta um estudo original das propriedades estruturais e eletrônicas dos nanotubos de carbono de parede simples (NTCPS) por meio de complexos de titânio e a possibilidade de adsorção e redução do cromo hexavalente Cr (VI) utilizando a teoria da densidade funcional. Cr (VI) é um dos principais poluentes ambientais, sua remoção apresenta várias dificuldades, e resulta em poluição ambiental, causando problemas de saúde. A adsorção de Cr (VI) foi investigada a partir das moléculas de cromato e dicromato no semicondutor NTCPS funcionalizado com complexos de TiO2, TiO4H4 e Ti2O6H4. Os resultados sugerem que os NTCPS funcionalizados são grandes candidatos à adsorção de Cr (VI). Além disso, as estruturas de banda eletrônica mudaram na região próxima à energia de Fermi das bandas de valência e de condução para os NTCPS pristino e funcionalizados com sistemas de cromo. Após adsorção de Cr (VI) nos sistemas, observa-se a formação de moléculas com menor toxicidade e atividade carcinogênica o que não ocorreu sem a presença dos nanotubos. / This thesis presents an original study of the structural and electronic properties of doped single-walled carbon nanotubes (SWCNT) through titanium complexes and the possibility of adsorption and reduction of hexavalent chromium Cr(VI) using density functional theory. Cr(VI) is one of the major environment pollutants, its removal presents several difficulties, and it results in industrial pollution, causing health problems. The adsorption of Cr(VI) was investigated from the chromate and dichromate molecules in semiconductor SWCNT functionalized with TiO2, TiO4H4 and Ti2O6H4 complexes. The results suggest that the functionalized SWCNT are great candidates to adsorb Cr(VI). In addition, the electronic band structures changed in the region near the Fermi energy of the valence and conduction bands for the pristine and functionalized SWCNT with chromium systems. After adsorption of Cr(VI) in the systems, the formation of molecules with less toxicity and carcinogenic activity is observed, which did not occur without the presence of the nanotubes.nanotubes.

Esta pesquisa tem como objeto de estudo a refuncionalização do espaço urbano através dos princípios que compõem a cidade criativa, tomando como ponto de partida o 4º Distrito de Porto Alegre – RS. O surgimento de grupos ligados à economia criativa, à economia do conhecimento e à economia da experiência promove uma transformação das funções urbanas, dialogando com a preservação das formas urbanas e do patrimônio histórico cultural. O 4º Distrito, região subutilizada na zona periférica do centro da cidade desde o processo de desconcentração industrial, é escolhido por esses profissionais em função dos baixos valores de troca do solo. A área ressurge como espaço central nas discussões sobre planejamento urbano a partir da possibilidade de retomada do seu crescimento econômico. Nesse âmbito, a pesquisa tem como objetivo compreender a ocorrência do processo de substituição de funções ligadas à indústria pela economia criativa, identificar qual a percepção dos grupos locais acerca da região e analisar como opera o planejamento estratégico nesse contexto Através de estudos relacionados à refuncionalização de áreas degradadas após a transição para a economia pós-fordista, e de entrevistas com empreendedores da economia criativa e moradores do 4º Distrito, se buscou compreender o caso da região como um fragmento de uma ordem mais ampla de revalorização do solo urbano nas áreas centrais. Com a ampliação de setores da economia ligados à informação e à cultura, considerados produtos centrais na primeira fase do Século XXI, promove-se a valorização de um fragmento histórico esquecido da cidade de Porto Alegre. A pesquisa aponta o pioneirismo da cidade criativa em um momento inicial do processo de refuncionalização da região. Posteriormente a essa dinâmica, o planejamento estratégico e as parcerias público-privadas se apresentam como caminhos para a revalorização do solo urbano. / This research's object of study is the re-functionalization of the urban space through the principles that make up the creative city, taking as a starting point the 4th District of Porto Alegre - RS. The emergence of groups linked to creative economy, knowledge economy and experience economy promotes a transformation of the urban functions, dialoguing with the preservation of urban forms and cultural-historical heritage. The 4th District, underutilized region in the peripheral zone of the city center since the process of industrial deconcentration, is chosen by these professionals due to the low soil exchange values. The area reappears as a central space in the discussions about urban planning based on the possibility of resuming its economic growth. In this scope, the research aims to understand the occurrence of the process of substitution of functions linked to the industry by creative economy, to identify the perception of local groups about the region and to analyze how the strategic planning operates in this context. Through studies related to the re-functionalization of degraded areas after the transition to post-Fordist economy, and through interviews with entrepreneurs of the creative economy and residents of the 4th District, an attempt was made to understand this case as a fragment of a broader revaluation order of urban land in central areas. With the expansion of sectors of the economy linked to information and culture, considered to be central products in the first phase of the XXI Century, it is promoted the valuation of a forgotten historical fragment of the city of Porto Alegre. The research points to the pioneering of the creative city in an initial moment of the process of re-functionalization of the region. Subsequent to this dynamic, strategic planning and public-private partnerships are presented as ways to revalue urban land.

Le procédé d’électro-filage est devenu une technique privilégiée pour la préparation des matériaux nano-fibreux, grâce à sa simplicité de mise en oeuvre, la polyvalence des matières premières utilisées, ainsi que la diversité des structures obtenues. Sa capacité à produire des réseaux fibrillaires, proches de ceux du vivant ont ouvert la voie à d’importantes applications en ingénierie tissulaire. Cette étude a porté sur i) l'élaboration de nano-fibres à base de biopolymères commerciaux par un procédé d’électro-filage, pour des applications en ingénierie tissulaire, ii) leur fonctionnalisation et, iii) l’étude par SANS de la stabilité des chaînes de polymères constituant ces fibres. La stabilité d’un polymère est un facteur important pour la dégradation contrôlée dans les systèmes biologiques. Des études de la stabilité de polystyrène, utilisé ici comme un modèle simple, dans le milieu confiné des nanofibres, ont été élaborés avec la technique de diffusion de neutrons aux petits angles. L’investigation de la conformation des chaînes de polymère dans les nanofibres montre une anisotropie remarquable, en suggérant une forte déformation des chaînes dans la direction axiale des fibres d’au cours de procédé d’électro-filage. La dynamique de relaxation des chaînes a permis d’évaluer leur stabilité et vieillissement dans le milieu confiné des nanofibres. Des fibres biocompatibles à base de poly(-caprolactone) (PCL) ont été électro-filées et optimisées pour obtenir des matériaux nano-structurés et fonctionnalisés en vue d’applications biomédicales. L’introduction par chimie click azide-alcyne de groupes saccharidiques dans le coeur ou en surface des fibres de PCL a été réalisée très efficacement selon deux approches distinctes avant ou après électro-filage. Les caractérisations physico-chimiques et biologiques réalisées sur les différents systèmes ont notamment permis de mettre en évidence la biodisponibilité des sucres à la surface des fibres ainsi que leur capacité à rendre la PCL hydrophile. Ces résultats attestent du potentiel de la chimie click à permettre la fonctionnalisation de fibres de polyesters sans altération de leur structure ouvrant ainsi d’importantes perspectives dans le domaine de l’ingénierie tissulaire. / Electrospinning process has become a leading technique for producing nano-fibrous scaffolds that are highly porous, lighter, and with superior mechanical properties than their bulk equivalents. Structural properties of electrospun fibers closely resemble to the connective cell tissue, making these nonwovens readily employed in medicine and pharmacy. The research study of this thesis focused on bridging the commercially available biopolymers with the tissue engineering applications through multifunctional aspects of carbohydrates and click chemistry coupling. Biocompatible fibers were electrospun from poly(-caprolactone) and further optimized into clickable azido-PCL scaffolds. Their surface-activity was visualized after click coupling of a fluorescent dye onto PCL-based electrospun fibers, while hydrophilicity and bioactivity were achieved by covalent bonding of carbohydrates, enabling specific cell adhesion possibilities of these nonwovens. Selective lectin surface-immobilization revealed the potential of these scaffolds for specific protein adhesion and therefore controlled cell-material interactions. Polymer stability is an important factor for controlled degradation in tissue engineering applications. Small angle neutron scattering studies were carried out to estimate the stability of polystyrene as a model-polymer, its chain conformation in as-spun and thermally annealed electrospun fibers. Notable anisotropy of polymeric chains within the fibers was observed. The terminal relaxation time of the polystyrene was estimated and compared to the theoretical value.

Ce mémoire est consacré à l'optimisation de la connexion enzymatique d'enzymes pour l'oxydation du glucose et la réduction de O2 sur matrices de nanotube de carbone (CNT) dans les biopiles à glucose.Premièrement, le transfert électronique indirect de la glucose oxydase (GOx) est optimisé dans une matrice nanostructurée de CNT contenant la 1,4-naphtoquinone comme médiateur rédox. Cette bioanode a ensuite été combinée avec des biocathodes similaires à bases d'enzymes à cuivre (laccase et tyrosinase). La biopile GOx-NQ/Lac a permis d'obtenir des puissances maximales de l'ordre de 1,5 mW.cm-2. Les utilisations de cette pile en décharge courte, longue et sa stabilité dans le temps ont également été étudiées. La seconde partie présente la préparation d'une autre anode basée sur la connexion indirecte d'une glucose déshydrogènase NAD+-dépendante (GDH-NAD+) comme alternative pour l'oxydation du glucose. La GDH-NAD+ a été combinée avec un catalyseur d'oxydation de NADH par différentes méthodes. Tout d'abord, elle a été encapsulée au sein du métallopolymère rédox, puis, la modification supramoléculaire a dans un second temps permis d'immobiliser le catalyseur moléculaire et l'enzyme à la surface des CNTs. Ces deux bioanodes ont permis respectivement l'obtention de courants catalytiques d'oxydation du glucose de 1,04 et 6 mA.cm-2. La seconde bioanode a été combinée avec une biocathode à base de BOD et a permis l'obtention de densités de courants maximales de l'ordre de 140 µW.cm-2 La dernière partie concerne l'élaboration d'une biocathode bienzymatique pour la réduction de O2. Le DET de la HRP sur CNTs a dans un premier temps été optimisé par modification de la surface par différents dérivés pyrène. Ensuite, la combinaison de la GOx et de la HRP sur la même électrode a permis de réduire efficacement O2 en 2 étapes. La biocathode est capable de délivrer une densité de courant maximale de l'ordre de 200 µA.cm-2. Cette dernière, combinée avec la bioanode GDH présentée précédemment a permis d'obtenir une biopile opérationnelle en conditions physiologiques et 10 mM de NAD+, en étant capable de débiter une densité de puissance maximale de l'ordre de 57 µW.cm-2. / This work focuses on the optimization of the electrical wiring of glucose oxidizing and dioxygen reducing enzymes on carbon nanotube (CNT) matrixes for glucose biofuel cells.In the first part, glucose oxidase (GOx) mediated electron transfer (MET) is optimized in nanostructured CNTs matrixes by mechanical compression of a CNTs/GOx composite containing 1,4-naphtoquinone as redox mediator. This bioanode was then combined with MCOs (laccase and tyrosinase) based biocathodes. The GOx-NQ/Lac biofuel cell was able to deliver a maximum power density of 1.5 mW.cm-2. The use of this biofuel cell in short/long time discharge and in storage has also been studied. The second part presents the preparation of another bioanode based on the indirect wiring of a NAD+-dependant glucose dehydrogenase (GDH-NAD+) as an alternative for glucose oxidation. The GDH-NAD+ has been combined with an NADH oxidation catalyst by two different techniques. The first one involves the encapsulation of the protein in the metallopolymer redox film, whereas the second one relies on the supramolecular modification of the CNTs by the molecular catalyst and the enzyme. Both bioanodes showed good catalytic properties toward glucose oxidation in presence of NAD+ with respectively 1.04 mA cm-2 and 6 mA cm-2. The latter has been combined with a BOD based biocathode to form a biofuel cell exhibiting maximum power densities of 140 µW cm-2. The last part of this work focuses on the design of a bienzymatic biocathode for O2 reduction. The DET of horseradish peroxidase (HRP) was first investigated and optimized by modification of the CNTs with pyrenes derivatives. The combination of the HRP with the GOx on the same electrode enables an efficient reduction of O2 in a 2-step process. The biocathode could exhibit maximum currents densities of 200 µA cm-2. This cathode along with the previous GDH bioanode formed a biofuel cell functional in physiological conditions and 10 mM NAD+ showing maximum power densities of 57 µW cm-2.

Ce travail de thèse porte, de manière globale, sur une meilleure compréhension du caoutchoucnaturel (NR). En effet, bien que ce matériau soit fortement utilisé dans l’industrie et ce depuisdes dizaines d’années, plusieurs de ses propriétés restent à ce jour mal comprises.Antérieurement à nos travaux, il a été fait un lien entre la biosynthèse du polymère et cespropriétés et il a été proposé que le caoutchouc naturel était constitué d’une chaînepolyisoprène (PI) 100% 1,4-cis de forte masse molaire (> 500 000 g/mol) fonctionnalisée en αet ω par une protéine et un motif phospholipidique respectivement. Ces bouts de chaîneseraient capables de s’auto-assembler pour créer un réseau physique qui confère au NR sespropriétés si intéressantes. L’objet de cette thèse a donc été de synthétiser un copolymère triblocProtéine/PI/Lipides afin de confirmer cette hypothèse en produisant en laboratoire unhomologue de NR. Pour ce faire, un PI hétéro-téléchélique cétone/aldéhyde a été obtenu pardégradation chimique de NR. Cette méthode a permis d’obtenir un PI 100 % 1,4-cis possédantdeux fonctions chimiques différentes en bout de chaine permettant ainsi le greffage sélectifd’une protéine où d’un motif lipidique. Ces deux couplages ont ensuite été étudiés séparément(PI/Protéine puis PI/Lipides) révélant des propriétés intéressantes dans le cas du copolymèredi-bloc PI/Lipide. Le couplage PI/Protéine s’est avéré plus compliqué et seul des copolymèresdi-blocs PI/Polypeptide ont pu être obtenus avec certitude, en utilisant des synthons PI commemacro-amorceurs. Une voie de synthèse a également été dégagée pour un tri-blockPolypeptide/PI/Lipide présentant une structure très proche du modèle de Tanaka. / This PhD work focuses on a better comprehension of natural rubber (NR). Indeed, despite thefact that this material has been used for a long time in industry, some properties remainunclear. Previous works of Tanaka allowed to make a link between the biosynthesis of thematerial and its properties. It was thus suggested that NR was composed of a high molar masschain of polyisoprene (PI, > 500 000 g/mol) functionalized at the α and ω chain-end by aprotein and a phospholipidic moiety respectively. These chain-ends would be able to selfassembleinto a pseudo-physical network which would explain some of the superior propertiesof NR. The goal of this PhD work is to synthesize a Protein/PI/Lipid tri-block copolymer inorder to check this hypothesis and to synthesize hybrid material close to NR. First, a 1,4-cishetero-telechelic (ketone/aldehyde) PI of 10 000 g/mol was obtained by chemical degradationof NR, yielding a polymeric chain bearing two different functions at the chain-ends, allowingto perform a selective functionalization with both a lipidic moiety and a protein. Both di-blockcopolymers (PI/Lipid and PI/Protein) were synthesized and studied separately. The PI/Lipiddi-block copolymer revealed interesting properties. The synthesis of PI/Protein di-blockcopolymer revealed more difficult and only PI/Polypeptide di-block copolymer could havebeen obtainded. To this end, PI macro-initiator allowed the Ring-Opening Polymerization odN-carboxyanhydride. Finally, a chemical pathway was established, allowing to synthesize aPolypeptide/PI/Lipid tri-block close to Tanaka’s model.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / In this Thesis we studied through first principles methods the effects of uniform transversal electric fields on the structural and electronic properties of carbon nanotubes. We study the formation of Si-doped carbon nanotubes through the interaction of Si with single-vacant nanotubes and investigate the action of electric fields on semiconducting and metallic carbon nanotubes, both pure carbon, carboxylated or Si-doped nanotubes. All investigations were done using computational first principles simulations based on the density functional theory using the SIESTA code. Firstly, we show that carbon nanotubes with single vacancies are highly reactive centers, which can be used as adsorbing sites for selected substances to form covalent bonds on surface. This feature is used to investigate the possibility of forming Si-doped carbon nanotube, analyzing possible energetic barriers and observing the steps of the structural rearrangement to the complete stabilization. The effect of the transversal electric field applied on carbon nanotubes was also investigated. The applied field has a remarkable influence on electronic structure of the semiconductor carbon nanotubes, leading to a band gap decreasing which is dependent on the field intensity and nanotube radius, including a possible semiconductormetal transition. It is also observed that the electric field induces electric polarization and a comparison between semiconductor and metal tubes is presented. In the same way, the action of transversal electric fields on semiconductor and metallic carbon nanotubes functionalized with carboxylic group was estimated. We observe that the presence of carboxyl in the nanotube surface modifies the response to the electric field, leading to considerable alterations on the electronic structure of the original system, such as energy bands, inducing an electric polarization and charge transfers between the adsorbed molecules and the carbon nanotube. Therefore, we also study the electric fields action on carboxylated Si-doped carbon nanotubes. The electronic and structural properties of these systems are analyzed and the results discussed. / Na presente Tese estudamos através de métodos de primeiros princípios os efeitos de campos elétricos uniformes transversais sobre as propriedades eletrônicas e estruturais de nanotubos de carbono. Apresentamos o estudo da formação de nanotubos de carbono dopados com Si através da interação com nanotubos apresentando vacâncias simples e investigamos a ação de campos elétricos sobre nanotubos de carbono semicondutores e metálicos, sejam eles puros, funcionalizados por ácido carboxílico ou dopados com Si. Toda investigação foi realizada através de simulações computacionais baseadas na teoria do funcional da densidade, utilizando-se, para tanto, o código computacional SIESTA. Uma revisão teórica dos métodos é apresentada, bem como as justificativas de emprego desta metodologia. Mostramos inicialmente que nanotubos de carbono apresentando vacâncias simples constituem um centro de alta reatividade, que pode ser empregado para adsorver substâncias de interesse e formar ligações covalentes com sua superfície. Utilizamos esta característica para investigar a possível formação de um nanotubo dopado com Si, analisando possíveis barreiras de energia e observando os diversos passos de rearranjo estrutural até a estabilização do sistema. Apresentamos, em seguida, os efeitos de campos elétricos transversais sobre nanotubos de carbono. Mostramos que campos elétricos transversais têm efeitos marcantes sobre a estrutura eletrônica de nanotubos semicondutores, provocando uma diminuição do gap de banda que depende da intensidade do campo aplicado e do raio do nanotubo, podendo ocorrer uma transição semicondutor-metal. Observamos que estes campos provocam uma polarização dos nanotubos, e apresentamos as diferenças observadas nesta resposta por nanotubos semicondutores e metálicos. Estudamos a ação de campos elétricos transversais sobre nanotubos semicondutores e metálicos funcionalizados com carboxila. Observamos que a presença deste grupo na superfície permite uma nova resposta aos campos elétricos, levando a alterações substanciais nas propriedades eletrônicas do sistema, como bandas de energia e densidades de estado, além de modificar a população eletrônica, levando à polarização do sistema. Finalizamos esta Tese com o estudo da ação de campos elétricos sobre nanotubos dopados com Si e com o sistema formado por um nanotubo dopado com Si e funcionalizados com ácido carboxílico. A influência destas modificações estruturais sobre as propriedades eletrônicas são apresentadas e os resultados, discutidos. Apresentamos, finalmente, as conclusões pertinentes a este trabalho, com suas implicações e possíveis conexões com a prática de realização experimental.

Submitted by Reginaldo Toshihiro Konatu (rtkonatu@gmail.com) on 2018-05-03T17:15:41Z No. of bitstreams: 1 Tese KONATU 2018.pdf: 3998865 bytes, checksum: 9ed8e8c75039aad725b37cff903fad84 (MD5) / Rejected by Pamella Benevides Gonçalves null (pamella@feg.unesp.br), reason: Solicitamos que realize correções na submissão seguindo as orientações abaixo: Você realizou duas submissões favor desconsiderar esta. Agradecemos a compreensão. on 2018-05-04T17:53:18Z (GMT) / Submitted by Reginaldo Toshihiro Konatu (rtkonatu@gmail.com) on 2018-05-04T18:50:12Z No. of bitstreams: 1 Tese Konatu 2018.pdf: 4232195 bytes, checksum: e32103c38cfbff0ac3d36adba585b7ad (MD5) / Approved for entry into archive by Pamella Benevides Gonçalves null (pamella@feg.unesp.br) on 2018-05-04T19:25:28Z (GMT) No. of bitstreams: 1 konatu_rt_dr_guara.pdf: 4232195 bytes, checksum: e32103c38cfbff0ac3d36adba585b7ad (MD5) / Made available in DSpace on 2018-05-04T19:25:28Z (GMT). No. of bitstreams: 1 konatu_rt_dr_guara.pdf: 4232195 bytes, checksum: e32103c38cfbff0ac3d36adba585b7ad (MD5) Previous issue date: 2018-03-06 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente trabalho tem como objetivo a obtenção de revestimentos poliméricos bactericidas formados por ácido hialurônico/quitosana/ZnO na superfície da liga Ti15Zr15Mo após crescimento de nanotubos de TiO2 empregando oxidação anódica. A liga Ti15Zr15Mo foi processada em forno a arco voltaico com atmosfera controlada e tratados termicamente. Os nanotubos de TiO2 foram obtidos por meio de oxidação anódica. Para obtenção dos revestimentos, as amostras foram recobertas com camadas de ácido hialurônico/quitosana/ZnO. As superfícies foram avaliadas empregando microscopia eletrônica de varredura (MEV), analise por difração de raios-X (DRX), espectroscopia de fotoelétrons excitados por raios-X (XPS) e ângulo de contato. A condição ideal para obtenção dos nanotubos ordenados de TiO2 na superfície da liga foi 30V, eletrólito formado por glicerol, água deionizada (1:1 em volume) e fluoreto de amônio (2,7 g/L) e tempo de 24 horas. Para esses parâmetros, os nanotubos formados apresentaram diâmetro médio de 130 nm e espessura de 1290 nm. O revestimento polimérico escolhido foi de 2 bicamadas de ácido hialurônico/quitosana contendo partículas de ZnO. Os estudos in vitro realizados para avaliar adesão bacteriana de Staphylococcus aureus mostraram que não houve diferença significativa entre as amostras com e sem recobrimento. / Nowadays the development of new materials for biomedical application has become of extreme importance due to the need of new materials with excellent mechanical properties, physicochemical and biocompatibility for use in the manufacture of biomedical devices. In addition to the material presenting the necessary bulk properties, it is of utmost importance that they present a response from the host to the implant. For this, the surface of the material must have characteristics that can be obtained with superficial treatments. This work aims at the analysis of the surface of nanotubes grown on the Ti15zr15Mo alloy functionalized with thin film of hyaluronic acid, chitosan and ZnO nanoparticles. The surface was analyzed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle. The nanotubes formed had a mean diameter of 130 nm and a thickness of 1290 nm. The coating with the polymeric bilayers, with a number of more than 4 bilayers, closed the nanotubes and increased the contact angle, being used 2 biacamadas for the incorporation of ZnO. The concentration of the ZnO solution was very low for incorporation and bactericidal effect.

L’analyse des radionucléides est une nécessité pour la gestion des matières et déchets radioactifs liée à l’industrie nucléaire. Pour éviter les interférences et améliorer la précision des mesures, les étapes de traitement de l’échantillon et de séparations restent aujourd’hui incontournables. Elles sont cependant longues, irradiantes, difficiles à mettre en œuvre en boite à gants et produisent un volume de déchets liquides et solides significatif. L’objectif de cette thèse est de proposer une alternative innovante à l’utilisation des colonnes d’extraction sur phase solide dans les protocoles de séparation des radionucléides en milieu nitrique concentré permettant de réduire ces déchets en fin de cycle analytique et d’automatiser ces étapes. Un premier microsystème jetable en plastique (COC) intégrant une micro-colonne séparative de chromatographie d’extraction a été conçu. La phase stationnaire est un monolithe poly(AMA-co-EDMA) synthétisé par photopolymérisation in situ à structure ajustable, fonctionnalisable à façon, résistant au milieu nitrique concentré. Les capacités d’échange obtenues sont de l’ordre de 150 mgU/g de monolithe pour le TBP et le mélange TBP/CMPO et 280 mgU/g de monolithe pour le DAAP. Les valeurs des coefficients de partage des monolithes imprégnés ont été déterminées pour U(VI), Th(IV), Eu(III) et Nd(III) pour les 3 extractants (ainsi que pour Pu(IV) dans le cas de monolithes imprégnés par le TBP). La synthèse du monolithe a été transférée en microsystème centrifuge et après étude hydrodynamique, la séparation U,Th/Eu en milieu nitrique a été réalisée sur colonne imprégnée TBP en microsystème classique puis transférée en microsystème centrifuge. / Radionuclides analysis is a key point for nuclear waste management and nuclear material control. Several steps of sample modification have to be carried out before measurements in order to avoid any interferences and improve measurement precision. However those different steps are long, irradiant and difficult to achieve in gloveboxes. Moreover they produce liquid and solid waste. The goal of the study is to offer a new alternative to the use of solid phase extraction column for radionuclides separation in hard nitric acid medium. The system will decrease the amount of nuclear waste due to the analysis and automatize the different steps of the analysis. A plastic device made of COC containing a micro solid phase extraction column is first designed. Stationary phase is a poly(AMA-co-EDMA) monolith synthetized in situ. Its structure is adjustable and its functionalization versatile with a high resistance to nitric acid medium. Exchange capacity is 150 mg/g of monolith for TBP and TBP/CMPO column and up to 280 mg/g of monolith in case of DAAP. Exchange coefficients are determined for U(VI), Th(IV), Eu(III) and Nd(III) for 3 different extractants (and Pu(IV) in case of TBP column). Monolith synthesis is transferred in centrifugal device and hydrodynamic behavior studied. U,Th/Eu separation was finally carried out in both classic and centrifugal microsystem on TBP column.

Dans cette thèse, nous décrivons sommairement les techniques utilisées qui sont l’imagerie parrésonance plasmon de surface (SPRi) et la diffusion Raman exaltée de surface (SERS). Le butprincipal du projet Piranex dans lequel la thèse s’inscrit consiste au développement d’une biopucenanostructurée bimodale permettant le couplage des deux techniques SPRi et SERS. Cettebiopuce est constituée d’un film d’or par-dessus lequel nous avons déposé un réseau carré denanocylindres en or. Un ensemble d’études ont été effectuées pour caractériser ses propriétésplasmoniques du biocapteur afin d’en optimiser le signal SERS. Nous avons ainsi constaté quel’émission du signal était fortement anisotrope, dus à l’excitation du Mode de Bragg et que lechamp proche était principalement exalté sur les bords de la nanostructure. Les propriétés furentégalement comparées avec celles de réseaux identiques déposés directement sur un substrat diélectrique.Par la suite un ensemble d’études plasmoniques et SERS ont été effectuées pourl’aluminium, autre matériaux plasmonique d’intérêt. Enfin, un protocole de détection par SERSde l’ochratoxine basé sur un aptamère fut développé et a permis la détection de l’ochratoxine dès10 pM, bien en dessous de la limite autorisée par les organismes de régulation en agroalimentaire. / In this thesis, we briefly describe the techniques used, which are surface plasmon resonanceimaging (SPRi) and surface enhanced Raman scattering (SERS). The main goal of the Piranexproject in which the thesis is based is the development of a bimodal nanostructured biochipallowing the coupling of the two techniques SPRi and SERS. This bio-chip consists of a goldfilm over which we have deposited a square array of gold nanocylinders. A set of studies hasbeen carried out to characterize plasmonic properties of the biosensor in order to optimize theSERS signal. We have thus found that the emission of the signal was strongly anisotropic, due tothe excitation of the Bragg Mode and that the near field was mainly enhanced on the edges of thenanostructure. The properties were also compared with those of identical gratings depositeddirectly on a dielectric substrate. Subsequently a set of plasmonic and SERS studies were carriedout for aluminum, other plasmonic materials of interest. Finally, a detection protocol by SERS ofochratoxin based on an aptamer was developed and allowed the detection of ochratoxin with adetection threshold of 10 pM, well below the limit allowed by food regulatory agencies