Tese de mestr.. Engenharia Mecânica. Faculdade de Engenharia. Universidade do Porto. 1998

Estágio realizado na CENTI e orientado pelo Doutora Andrea Carneiro / Tese de mestrado integrado. Engenharia Química. Faculdade de Engenharia. Universidade do Porto. 2009

La thermoélectricité rencontre un intérêt croissant ces dernières années comme source d'énergie alternative pour l’alimentation de dispositifs micro- et nano- électroniques. Les matériaux thermoélectriques transforment par effet Seebeck une différence de température en énergie électrique utile. Dans les dispositifs thermoélectriques, l’énergie perdue en général sous forme de chaleur résiduelle peut ainsi être recyclée en utilisant les gradients de température existants. L'efficacité thermoélectrique dépend des propriétés électroniques du matériau et de sa conductivité thermique κ. Le silicium présente une très bonne conductivité électrique et un coefficient Seebeck prometteur, mais sa conductivité thermique phononique limite fortement son potentiel pour des applications thermoélectriques, du moins sous forme de matériau massif. Par contre, la nanostructuration du silicium en couches minces, et a fortiori la fabrication de cristaux phononiques permet de réduire fortement la conductivité thermique. Dans ce travail, des simulations de dynamique moléculaire sont réalisées pour confirmer cette stratégie et permettre la définition d'un design optimal de membranes perforées. De plus, le travail expérimental montre différentes méthodologies de fabrication de membranes phononiques de silicium intégrées dans une plate-forme de métrologie. Plusieurs techniques de caractérisation (Electrothermique, Raman et Microscopie à sonde thermique) ont ensuite été utilisées pour déterminer la conductivité thermique des membranes. Une réduction considérable de κ est obtenue pour le silicium, permettant d’envisager l’intégration de ces membranes dans un convertisseur thermoélectrique. / In the last twenty years, the continuous seek for alternative energy sources to power micro- and nano-electronic devices has marked the rise of interest toward thermoelectricity. Thermoelectric materials can turn directly, by Seebeck effect, the temperature difference into useful electric power. The energy lost as waste heat can be re-used as a power source. It is known that, to improve thermoelectric efficiency, an important role is played by material’s electronic properties and its thermal conductivity. Silicon exhibits very good electrical conductivity and Seebeck parameter, but its lattice thermal conductivity represents the bigger obstacle for thermoelectric applications, preventing its direct integration as bulk material. It has been demonstrated that nanostructuring silicon in thin films enables the reduction of thermal conductivity down to one order of magnitude. Furthermore, a supplementary decrease of thermal conductivity is possible by periodical patterning of the silicon thin film in a photonic-like way, creating Phononic Crystals (PnCs). In our work molecular dynamics simulations are performed to confirm the trend envisaged and allow the definition of an optimal design for the patterned membranes. Moreover, our experimental work lists different fabrication methodologies of silicon phononic engineered membranes integrate into a metrology platform. Several characterization techniques (Electrothermal , Raman thermometry, Scanning Thermal Microscopy) are used to determine the membranes thermal conductivity. A considerable reduction of κ is obtained for silicon, paving the way for a prospective integration of those membranes into a thermoelectric converter.

Depuis les années 2000, le développement de la spectroscopie Raman à exaltation de pointe (TERS) a permis l’accès de manière extrêmement localisée aux propriétés structurales et moléculaires à la surface de la matière et à des analyses physico-chimiques combinées. La technologie TERS associe les techniques de microscopie à sonde locale - ici le microscope à force atomique (AFM) - avec le champ proche optique. Elle bénéficie en particulier de la génération, à la surface métaux nobles, de plasmons de surface à l’origine d’exaltation d’ondes électromagnétiques pouvant être confinées dans un volume sub-longueur d'onde à l'extrémité des sondes AFM-TERS. Aujourd'hui le principal verrou technologique en TERS est la conception des sondes AFM en termes de reproductibilité à échelle nanométrique, et de fabrication en série. Ce travail de thèse effectué dans le cadre d’une thèse CIFRE (HORIBA Scientific) a eu pour but de concevoir un nouveau type de sonde AFM-TERS répondant aux exigences de performances et de fabrication actuelles. Pour atteindre cet objectif, une étude de simulation numérique a conduit à proposer une nanostructuration métallique de l’extrémité d’un levier AFM, afin de conduire à une exaltation électromagnétique optimisée. Un procédé de nano- et micro-fabrication a été développé au sein de la plateforme de micro et nano-fabrication de l'IEMN, combinant lithographie électronique et optique, évaporation métallique et gravure sur wafers silicium. Il permet la réalisation en série de sondes AFM dont chaque extrémité est composée d'une nano-antenne métallique de taille sub-longueur d'onde, composée d'un nanodisque supportant un nanocône. La méthode de fabrication proposée permet un contrôle des réponses plasmoniques en termes d’amplification du champ et d’accordabilité de la résonance, qui sont la clé des performances en spectroscopie Raman à exaltation de pointe. Une étude sur l’évaporation inclinée lors du procédé de nano-fabrication développé par lithographie électronique a également été réalisé dans le but de contrôler la forme des nanoparticules – de forme conique à cylindrique avec des parois poreuses -- isolées ou en réseaux denses. Les simulations numériques suggèrent que de tels objets peuvent être des candidats potentiels pour le TERS ou le SERS (spectroscopie Raman à exaltation de surface). / Since the start of the 2000s the evolution of tip-enhanced Raman spectroscopy (TERS) has enabled the simultaneous measurement of localized structural, molecular, and physicochemical properties. TERS technology combines scanning probe microscopy -- atomic force microscopy (AFM) -- with near field optical microscopy. The combined technique is referred to as AFM-TERS. The technique harnesses and exploits the generation of surface plasmons on metal surfaces. These plasmons lead to the generation of confined electromagnetic waves in a sub-wavelength volume at the very tip of the AFM-TERS probe. The main technological challenge today is the design and optimization of an AFM-TERS probe having nanometer-sized dimensions -- and the controlled, reproducible batch fabrication of such structures. The objective of the work presented in this PhD thesis was to design, fabricate, and characterize a new type of AFM probe capable of bettering the current state-of-the-art performances. The PhD was carried out in collaboration with HORIBA and funded partly by a French ‘CIFRE’ grant. In order to meet these objects, comprehensive numerical modelling led to the design of an optimized metal nanostructuring having maximum electromagnetic exaltation -- placed at the extremity of a silicon-based AFM cantilever. A new combined micro and nano fabrication process was developed to achieve this -- to be performed using the existing equipment found in the IEMN cleanroom. The process encompasses techniques such as masking using electron beam (ebeam) lithography and UV photolithography, thermal evaporation of metals and ‘lift-off’ techniques, and highly-controlled dry etching of small silicon mesas structures and deep etching for MEMS cantilever releasing. The process enables the batch-fabrication manufacture of AFM-TERS probes containing matter on the millimeter scale (the silicon probe support), the micrometer scale (the silicon cantilever), and the nanometer scale (the combined metallic disk and cone having sub-wavelength dimensions). This method allows nanostructuring on the optical/plasmonic behavior of TERS probes, the key factor which will lead to higher performance in TERS. Finally, a further study concerning the inclined evaporation of metallic nanostructures via an ebeam-derived lithographic shadow mask was performed in order to control the size and shape of the nanostructuring. The study proved this approach to be feasible. Furthermore, numerical modelling of such structures suggests that they are potential original candidates for both TERS and SERS (surface-enhanced Raman spectroscopy).

La présentation de mes activités de recherche et d'encadrement qui fait l'objet de ce document est organisée autour de trois thèmes scientifiques :<br>- les interactions entre un laser impulsionnel et des matériaux en régimes nano-, pico-, et femtoseconde (Chapitre 1)<br>- l'expansion d'un panache plasma créé par laser impulsionnel sous vide ou dans un gaz ambiant (Chapitre 2)<br>- la formation de nano agrégats par impulsions laser et l'interaction laser avec des nano-agrégats (Chapitre 3)

Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers and plays a critical role in tumor growth and cancer immune evasion. The focus of this dissertation is the delivery of STAT3 inhibitor cucurbitacins to tumors using polymeric nano-carriers for the inhibition of tumor growth and modulation of tumor-induced immunosuppression. The anticancer and immunomodulatory activity of STAT3 inhibitor JSI-124 (cucurbitacin I) was studied in mice carrying B16 tumor. The results showed that JSI-124 + CpG or 7-acyl lipid A combination therapy modulated immunosuppression in tumor environment and generated superior anti-tumor effects compared to monotherapy. In further studies, a sensitive and reproducible liquid chromatography-mass spectroscopy (LC-MS) method was developed and validated for quantitative analysis of STAT3 inhibitor cucurbitacins in vitro and in biological samples. Moreover, nano-delivery systems based on poly(ethylene oxide)-block-poly(-caprolactone) (PEO-b-PCL) micelles and its analogues containing physically encapsulated cucurbitacin and poly(D,L -lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing chemically conjugated JSI-124 for the delivery of STAT3 inhibitor to tumor and dendritic cells (DCs) were developed and characterized. Polymeric micelles of different PCL based core structure were able to significantly increase the water solubility of STAT3 inhibitor cucurbitacins, and slow the rate of drug release by a diffusion dependent mechanism. The chemical structure of the micellar core was found to control the release rate of cucurbitacin from the micelles. PLGA NPs containing conjugated JSI-124, on the other hand, demonstrated a degradation dependent drug release profile over a 1-month period. Both nanoparticulate formulations exhibited potent anticancer and STAT3 inhibitory activity against B16 cancer. Moreover PLGA-JSI-124 NPs suppressed STAT3 activation in immunosuppressed p-STAT3highDCs and significantly improved their function in stimulating T cell proliferation in vitro. These findings show that JSI-124 esters of PLGA NPs can potentially provide a useful platform for JSI-124 delivery to tumor and its targeted delivery to DCs. The results of this research not only proved the principle of STAT3 inhibition in tumors as an efficient intervention for enhancing the therapeutic efficacy of TLR ligand-based cancer immunotherapy, but led to development of nano-delivery systems with potential application in cancer chemo-and immunotherapy. / Pharmaceutical Sciences

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Solid oxide fuel cells (SOFCs) are considered as one of the most promising power generation technologies due to their high energy conversion efficiency, fuel flexibility and reduced pollution. There is a broad interest in reducing the operating temperature of SOFCs. The key issue to develop low-temperature (300~600 °C) SOFCs (LTSOFCs) is to explore new electrolyte materials. Recently, ceria-based composite electrolytes have been developed as capable alternative electrolyte for LTSOFCs. The ceria-based composite electrolyte has displayed high ionic conductivity and excellent fuel cell performance below 600 °C, which has opened up a new horizon in the LTSOFCs field. In this thesis, we are aiming at exploring nanostructured composite materials for LTSOFCs with superior properties, investigating the detailed conduction mechanism for their enhanced ionic conductivity, and extending more suitable composite system and nanostructure materials.In the first part, core-shell samarium doped ceria-carbonate nanocomposite (SDC/Na2CO3) was synthesized for the first time. The core-shell nanocomposite was composed of SDC particles smaller than 100 nm coated with amorphous Na2CO3 shell. The nanocomposite has been applied in LTSOFCs with excellent performance. A freeze dry method was used to prepare the SDC/Na2CO3 nanocomposites, aiming to further enhance its phase homogeneity. The ionic conduction behavior of the SDC/Na2CO3 nanocomposite has been studied. The results indicated that H+ conductivity in the nanocomposite is predominant over O2- conductivity with 1-2 orders of magnitude in the temperature range of 200-600 °C, indicating the proton conduction in the nanocomposite mainly accounts for the enhanced total ionic conductivity. The influence of Na2CO3 content to the proton and oxygen ion conductivity in the nanocomposite was studied as well.In the second part, both the proton and oxygen ion conduction mechanisms have been studied. It is suggested that the interface in the nanocomposite electrolyte supplies high conductive path for the proton, while oxygen ions are probably transported by the SDC grain interiors. An empirical “Swing Model” has been proposed as a possible mechanism of superior proton conduction, while oxygen ion conduction is attributed to oxygen vacancies through SDC grain in nanocomposite electrolyte.In the final part, a novel concept of non-ceria-salt-composites electrolyte, LiAlO2-carbonate composite electrolyte, has been investigated for LTSOFCs. The LiAlO2-carbonate electrolyte exhibits good conductivity and excellent fuel cell performances below 650 °C. The work not only developed a more stable composite material, but also strongly demonstrated that the high ionic conductivity is mainly related to interface effect between oxide and carbonate. As a potential candidate for nanocomposite, uniform quasi-octahedral CeO2 mesocrystals was synthesized in this thesis work as well. The CeO2 mesocrystals shows excellent thermal stability, and display potential for fuel cell applications. / <p>QC 20120529</p>

Gene therapy holds the unprecedented potential to treat disease by manipulating the underlying genetic blueprints of phenotypic behavior. Targeting of gene delivery is essential to achieve specificity for the intended tissue, which is especially critical in cancer gene therapy to avoid destruction of healthy tissue. Adeno-associated virus (AAV) is considered the safest viral vector and, compared to non-viral vectors, offers several advantages: higher efficiency, genetic modification, combinatorial panning, and high monodispersity. Classic viral targeting has focused on engineering ligand-receptor interactions, but many cell surface targets do not support post-binding transduction events. Furthermore, many potential target tissues – such as triple negative breast cancer – may not display a single, unique identifying surface receptor, so new methods of targeting are needed. Alternatively, many pathological states, including most cancers, exhibit upregulation of proteolytic enzymes in the extracellular milieu. The present work describes the development of an AAV platform that has been engineered to activate in response to disease-related proteases. The specificity and sensitivity of these protease-activatable viruses (PAVs) can be tuned to meet the demands of various clinical scenarios, giving the platform some therapeutic versatility. This work represents the first demonstration of a protease-controlled, non-enveloped virus for genetic therapy. These results extend the therapeutic value of AAV, the safest gene vector currently being explored in 73 clinical trials worldwide.

This thesis is about "nano-cellular" polymer foams, i.e., to understand nano-bubble nucleation and growth mechanisms, we used Self-Consistent Field Theory(SCFT) for the research.\\ Classical Nucleation Theory (CNT) is often used to calculate nucleation rates, but CNT has assumptions which break down for a nano-sized bubble: it assumes planar sharp interfaces and bulk phases inside bubbles. Therefore, since the size of a nano-sized bubble is comparable to the size of the polymer molecule, we assumed that a bubble surface is a curved surface, and we ivestigated effects of curvature on the nucleation barrier. SCFT results show that sharper curvatures of smaller s cause a higher polymer configurational entropy and lower internal energy, and also the collapse of the bulk phase for smaller bubbles causes low internal energy. Consequently, the homogenous bubble nucleation barrier for curved surfaces is much smaller than flat surface (CNT prediction).\\ We calculated direct predictions for maximum possible cell densities as a function of bubble radius without calculation of nucleation barrier or nucleation rates in CNT. Our results show higher cell densities at higher solvent densities and lower temperatures. Moreover, our cell density prediction reveals that rather than surface tension, the volume free energy, often labelled as a pressure difference in CNT, is the dominant factor for both cell densities and cell sizes. This is not predicted by CNT.\\ We also calculated direct predictions for the maximum possible cell densities as a function of system volume in compressible systems. With an assumption that system pressure has an optimal pressure which gives the maximal density of good quality foams (bulk phase inside bubble), we calculated the inhomogeneous system pressure, the homogeneous system, and cell density as a function of system volume.\\ Maximal cell prediction in compressible system shows the incompressible system prediction is the upperbound maximal cell density, and qualitatively consistent with the compressible system results - higher cell densities at low temperatures and high solvent densities.\\ In addition, our results show a bigger expansion as well as a high cell density at low temperature and high solvent density, but temperature is a more dominant factor than the solvent density. From our results, we assume that a quick pressure dropping is required to get a better quality foam of a higher cell density.