Ce travail de thèse est consacré au développement d’un dispositif autarcique pour le contrôle des amphétamines dans les égouts. Il a été conçu dans le cadre du projet européen MicroMole pour aider la police scientifique à résoudre des scènes concernant la localisation des laboratoires clandestins d’amphétamines et produits dérivés. Il est composé de trois volets : le premier volet est dédié au développement de deux générations de capteurs potentiométriques sélectifs à l’amphétamine en utilisant le ionophore commercial dibenzo-18-crown-6 éther dans un premier temps puis le ion-pair complexe [amphetamine-H]+[3,3’-Co(1,2-C2B9H11)2]- synthétisé comme sites actifs pour la reconnaissance sélective d’amphétamine. Le deuxième volet est consacré au développement d’un système microfluidique passif permettant de contrôler le flux d’échantillon arrivant à la partie sensible du capteur en utilisant des micro-filtres et micro-mélangeurs. Le troisième et dernier volet est dédié à la conception et fabrication d’un système autonome d’échantillonnage miniaturisé pour le stockage des échantillons dans les égouts lors des enquêtes menées par la police scientifique correspondant à la localisation de laboratoires clandestins d’amphétamines / The work in this thesis is devoted to the development of an autarkic device for real-time monitoring of amphetamines in sewage. It has been developed within the EU project Micromole to help Law Enforcement Agents (LEA) to solve forensic scenarios related to the production of amphetamines and amphetamine-type stimulants (ATS). It is composed of three main sections. The first section is devoted to the development of two generation of potentiometric sensors for the detection of amphetamines using first, the commercial ionophore dibenzo-18-crown-6 ether, then the synthesized ion-pair complex [amphetamine-H]+[3,3’-Co(1,2-C2B9H11)2]- as active sites for amphetamine recognition. The second section is dedicated to the fabrication of a passive microfluidic system integrated into a Lab-on-a-Chip to protect the sensor from the harsh environment through the control of the sample amount reaching the sensor. For this purpose, the microfluidic system formed a combination of passive micromixers, microfilters and microchannels. The final section was devoted to the development of an autarkic sample storage unit to help LEA to store spontaneous samples during forensic investigations related to the clandestine production of amphetamines in illegal laboratories

Como a experiência estética pode ampliar as condições de escuta, leitura e compreensão do mundo? O objetivo desta pesquisa é trazer à luz o campo da criação artística como analogia da construção sensível do ser humano e a constituição de sua visão de mundo. Espera-se poder refletir sobre como o trabalho artístico se relaciona com processos subjetivos, conduzindo à transformação de aspectos psicológicos. Tomaremos a abordagem do Construtivismo Semiótico-Cultural em Psicologia como possibilidade de mediação de um diálogo entre Artes Cênicas e Psicologia, para a compreensão de processos e modos híbridos de criação, com o intuito de poder contribuir com procedimentos que abarquem estratégias de intervenção em Psicologia. Utilizaremos como material empírico os registros da atividade artístico-pedagógica do pesquisador que atua como artista-orientador do Programa Vocacional da Prefeitura da cidade de São Paulo. A forma de análise dos resultados prezará pela compreensão do acontecimento artístico em sua interdependência e interrelação com a pessoa e inserida dentro de seu campo social. São feitas reflexões sobre os procedimentos do processo de criação que envolve a elaboração de protocolos, depoimentos, entrevistas, ações culturais, construção de cenas como produtos artísticos que aparecem, ressoam e ressignificam a vida cotidiana. Consideramos que a experiência vivida da criação artística funde-se a uma pessoa também em construção, que vivencia, num espaço-tempo codificado, outras possibilidades e relações, percebe no advento do artifício sua incompletude como potencialidade latente de reinventar sua própria realidade / How can aesthetic experience enhance the conditions of listening, reading and understanding of the world? The objective of this research is to bring to light the field of artistic creation as an analogy of the sensitive construction of human being and his/her worldview constitution. It is expected that we can reflect on how the artistic work relates to subjective processes, which leads to the transformation of psychological aspects. We will take the approach of Semiotic- Cultural Constructivism in Psychology as the possibility of mediation of a dialogue between Performing Arts and Psychology, in order to understand of processes and hybrid forms of creation, intending to being able to contribute to procedures that cover strategies of intervention in Psychology. As empirical material, we will use the researchers who works as a tutor-artist in the Vocational Program of the city of Sao Paulo artistic-pedagogical activity records. The form of analysis of the results will focus the understanding of the artistic happening in its interdependence and interrelationship with the person, and inserted within his/her social field. We reflect on the procedures of the creation process that involves the elaboration of protocols, testimonies, interviews, cultural actions, and the construction of scenes as artistic products that appear, resonate and resignify day-to-day life. We consider the lived experience of artistic creation merges with a person who is also under construction, who experiences, in a codified space-time, other possibilities and relations, perceives in the advent of artifice his/her incompleteness as latent potentiality to reinvent his/her own reality

As the microelectronics industry pushes microfabrication processes further, the lab-on-a-chip field has continued to piggy-back off the industry's fabrication capabilities with the goal of producing total chemical and biological systems on small chip-size platforms. One important function of such systems is the ability to perform single molecule detection. There are currently many methods being researched for performing single molecule detection, both macro and micro in scale. This dissertation focuses on an optofluidic, lab-on-a-chip platform called the ARROW biosensor, which possesses several advantages over macro-scale single molecule detection platforms. These advantages include an amplification-free detection scheme, cheap parallel fabrication techniques, rapid single molecule detection results, and extremely low volume sample probing, which leads to ultra-sensitive detection. The ARROW biosensor was conceived in the early 2000s; however, since then it has undergone many design changes to improve and add new functionality to the lab-on-a-chip; however, water absorption in the plasma enhanced chemical vapor deposited silicon dioxide has been a problem that has plagued the biosensor platform for some time. Moisture uptake in the oxide layer of the ARROWs leads to loss of waveguiding confinement and drastically decreases the overall sensitivity of the ARROW biosensors. New ARROW designs were investigated to alleviate the negative water absorption effects in the ARROWs. The new waveguide designs were tested for resiliency to water absorption and the buried ARROW (bARROW) design was determined to be the most successful at preventing negative water absorption effects from occurring in the PECVD oxide waveguides. The bARROWs were integrated into the full biosensor platforms and used to demonstrate high sensitivity single molecule detection without any signs of water absorption affecting the bARROWs' waveguiding capabilities. The bARROW biosensors are not only water resistant, they also proved to be the most sensitive biosensors yet fabricated with average signal-to-noise ratios around 80% higher than any previously fabricated ARROW biosensors.

Including inherited genetic diseases, like lipoprotein lipase deficiency, and acquired diseases, such as cancer and HIV, gene therapy has the potential to treat or cure afflicted people by driving an affected cell to produce a therapeutic protein. Using primarily viral vectors, gene therapies are involved in a number of ongoing clinical trials and have already been approved by multiple international regulatory drug administrations for several diseases. However, viral vectors suffer from serious disadvantages including poor transduction of many cell types, immunogenicity, direct tissue toxicity and lack of targetability. Non-viral polymeric gene delivery vectors (polyplexes) provide an alternative solution but are limited by poor transfection efficiency and cytotoxicity. Microfluidic (MF) nano-precipitation is an emerging field in which researchers seek to tune the physicochemical properties of nanoparticles by controlling the flow regime during synthesis. Using this approach, several groups have demonstrated the successful production of enhanced polymeric gene delivery vectors. It has been shown that polyplexes created in the diffusive flow environment have a higher transfection efficiency and lower cytotoxicity. Other groups have demonstrated that charge-stabilizing polyplexes by sequentially adding polymers of alternating charges improves transfection efficiency and serum stability, also addressing major challenges to the clinical implementation of non-viral gene delivery vectors. To advance non-viral gene delivery towards clinical relevance, we have developed a microfluidic platform (MS) that produces conventional polyplexes with increased transfection efficiency and decreased toxicity and then extended this platform for the production of ternary polyplexes. This work involves first designing microfluidic devices using computational fluid dynamics (CFD), fabricating the devices, and validating the devices using fluorescence flow characterization and absorbance measurements of the resulting products. With an integrated separation mechanism, excess polyethylenimine (PEI) is removed from the outer regions of the stream leaving purified polyplexes that can go on to be used directly in transfections or be charge stabilized by addition of polyanions such as polyglutamic acid (PGA) for the creation of ternary polyplexes. Following the design portion of the research, the device was used to produce binary particle characterization was carried out and particle sizes, polydispersity and zeta potential of both conventional and MS polyplexes was compared. MS-produced polyplexes exhibited up to a 75% reduction in particle size compared to BM-produced polyplexes, while exhibiting little difference in zeta potential and polydispersity. A variety of standard biological assays were carried out to test the effects of the vectors on a variety of cell lines – and in this case the MS polyplexes proved to be both less toxic and have higher transfection efficiency in most cell lines. HeLa cells demonstrated the highest increase in transgene expression with a 150-fold increase when comparing to conventional bulk mixed polyplexes at the optimum formulation. A similar set of experiments were carried out with ternary polyplexes produced by the separation device. In this case it was shown that there were statistically significant increases in transfection efficiency for the MS-produced ternary polyplexes compared to BM-produced poyplexes, with a 23-fold increase in transfection activity at the optimum PEI/DNA ratio in MDAMB-231 cells. These MS-produced ternary polyplexes exhibited higher cell viability in many instances, a result that may be explained but the reduction in both free polymer and ghost particles.

Lorsque des ondes acoustiques de surface rayonnent dans des fluides, elles provoquent deux effets non linéaires : la pression de radiation et le streaming acoustique. Ces deux effets ont trouvé un grand nombre d’applications pour la microfluidique digitale, la manipulation sans contact et le tri cellulaire. Néanmoins, ces systèmes se heurtent à deux limites. D’une part, chaque application requiert une onde acoustique spécifique : il n’existe pas de dispositif multifonction à ce jour. D’autre part, l’exploration des fonctionnalités offertes par les ondes de surface les plus simples (ondes planes, ondes focalisées) n’a pas permis de réaliser des pinces sélectives permettant de manipuler individuellement des particules ou cellules indépendamment de leurs voisines.Dans une première partie de la thèse, nous développons deux méthodologies pour synthétiser des champs complexes d’ondes de surface. La première méthode utilise un réseau de 32 peignes interdigités contrôlé par la technique du filtre inverse pour générer des champs sur demande. La seconde résout un problème inverse afin de concevoir un transducteur holographique générant spécifiquement le champ demandé. Dans la seconde partie de la thèse, nous utilisons le filtre inverse pour (i) réaliser un laboratoire sur puce multifonction et (ii) étudier le potentiel d’ondes de surface particulières appelées ondes de surface tourbillonnaires. Ces ondes permettent une manipulation sélective et sans contact d’objets microscopiques. Nous terminons la thèse en équipant un microscope d’un transducteur holographique de vortex acoustiques afin de réaliser une manipulation sélective et sans contact de cellules. / When surface acoustic waves radiate in nearby fluids, they trigger two nonlinear effects: acoustic radiation pressure and acoustic streaming. These two effects find numerous applications for digital microfluidics, contactless manipulation and biological cell sorting. Nonetheless, these systems face two limitations. On the one hand, each application requires a specific acoustic wave: there is no multifunction device so far. On the other hand, search for functionalities offered by simple surface acoustic waves (plane and focused waves) has failed to provide a selective tweezers able to manipulate individual particles or cells independently of their neighbors. In the first part of this thesis, we develop two methods to synthesize complex surface acoustic wave fields. The first one employs an array of 32 interdigitated transducers controlled by the inverse filter to generate arbitrary fields on demand. The second method solves an inverse problem to design a holographic transducer to generate a predefined field. In the second part of the thesis, we use the inverse filter to (i) implement a multifunction lab on a chip and (ii) investigate the potentialities of a special type of surface acoustic waves called swirling surface waves. These waves enable a selective and contactless manipulation of microscopic objects. We conclude the thesis by integrating a holographic acoustical vortex transducer on a microscope in order to selectively manipulate biological cells without contact.

Ce travail de thèse a pour but de développer un dispositif basé autour d'un dispositif intégré de photodétection pour des applications biomédicales nécessitant une grande sensibilité de détection et une discrimination spectrale (sélectivité). Ce dispositif peut être appliqué, par exemple, à la mesure simultanée de plusieurs marqueurs fluorescents dans les laboratoires sur puce mettant en œuvre de très faibles volumes de réactifs (inférieurs au microlitre). Le travail de thèse se focalise sur la conception, la réalisation et le test de ce dispositif intégré de photodétection. Ce travail se décline selon deux axes principaux : d'une part, la conception d'un photodétecteur CMOS avec préamplificateurs intégrés, et d'autre part la conception, la réalisation et la caractérisation de filtres optiques intégrés performants pour la détection de fluorescence / This thesis aims to develop a system based around an integrated photosensor device for biomedical applications requiring high detection sensitivity and spectral discrimination (selectivity). For example, this system can be applied to mesure simultaneous emissions of several fluorescent labels in lab-on- a-chip implementing very small volumes of reagents (below the microliter). The thesis focuses on the design, implementation and testing of this integrated photodetector device. The work is divided in two main parts: first, the design of a CMOS photodetector with integrated preamplifiers, and secondly the design, realization and characterization of integrated optical filters for fluorescence detection

Résumé confidentiel / Résumé confidentiel

Afin de réaliser des dispositifs en polymère à forte valeur ajoutée, l'industrie de la plasturgie s'intéresse depuis quelques années à la convergence possible entre les microtechnologies et les méthodes industrielles de mise en oeuvre des polymères (le thermoformage et la thermo-injection). Dans ce contexte, l'objectif de cette thèse est de démontrer l'intérêt d'une approche à base de microtamponnage pour l'intégration de capteurs à base métallique dans des circuits microfluidiques en thermoplastique réalisés par thermoformage. Pour ces matériaux, cette approche apparait plus pertinente en terme de production de masse qu'une approche de photolithographie classique. Nous avons choisi de démontrer ce concept en étudiant l'intégration d'un capteur de pH et d'un capteur de température dans un système microfluidique en copolymère d'oléfine cyclique (COC) réalisé par thermoformage. En effet, la mesure de ces paramètres physico-chimiques est extrêmement répandue dans différents domaines d'application allant de la chimie à la biologie et à la médecine. Pour le capteur de pH, nous avons développé une couche sensible au pH à base d'oxyde d'iridium (IrOx) électrodéposé sur or. L'influence de différents paramètres (solution d'électrodépôt, méthode d'électrodéposition, nature du substrat métallique et son mode de préparation) sur la réponse au pH de ces couches a été étudiée. Nous avons ainsi pu démonter qu'une approche par microtamponnage passive est adaptée à la préparation de capteurs de pH sur un substrat en COC/Au ayant une sensibilité de -72 mV/pH et une durée de vie de 1 an. Pour le capteur de température, la solution retenue est basée sur le principe d'une thermorésistance. Les capteurs ont été élaborés en utilisant une approche par microtamponnage actif avec croissance d'une couche de nickel (dont l'épaisseur varie entre 0,2 et 5 μm) par métallisation autocatalytique sur polyimide. La dérive des capteurs est actuellement trop importante pour une application pratique. Finalement, des résultats préliminaires d'intégration de ces capteurs dans un microsystème fluidique thermoformé sont présentés avec notamment une configuration originale de mesure différentielle du pH / The plastics industry has been interested for some years in the possible convergence between microtechnologies and conventional polymer manufacturing (hot embossing and injection molding). In this context, this thesis aims at demonstrating the potential of a process based on microcontact printing in order to integrate metal based sensors in thermoplastic microfluidic devices shaped by hot embossing. For the mass production of thermoplastic devices, this approach appears more relevant than conventional photolithography. We chose to demonstrate this concept by investigating the integration of both a pH sensor and a temperature sensor in a thermoformed Cyclo Olefin Copolymer (COC) microfluidic system. Indeed, the measurement of these physicochemical parameters are extremely widespread in different applicative areas ranging from chemistry tobiology and medicine. For the pH sensor, we developed a pH-sensitive layer based on electrodeposited iridium oxide (IrOx) on Au. The influence of various parameters (plating solution and method , nature of the metal substrate and its method of preparation) on the pH response of these layers was studied. We were able to demonstrate that microcontact printing based on a passive approach is suitable for the preparation of pH sensors on a COC substrate with a sensitivity of -72 mV/pH and a 1 year lifetime. As regards the temperature sensor, the solution was to design a thermistor. Sensors were implemented with an approach based on active microcontact printing followed by electroless deposition of nickel (thickness varies between 0,2 and 5 μm) on polyimide. The drift of these sensors is too large for practical application. Finally, preliminary results presenting the integrating of these sensors in a fluidic microsystem are reported using an original configuration based on differential measurement of pH

Les charges à l'interface liquide/solide sont un élément originel majeur des phénomènes électrocinétiques observés en micro/nanofluidique. Elles sont donc la colonne vertébrale de mon manuscrit de thèse, qui se décompose en trois parties : Dans la première partie, un rappel des concepts de base sur les interfaces liquides/solides est proposé au lecteur. Il est suivi d'une description des différentes méthodes expérimentales permettant de mesurer le potentiel zeta de couples solide/électrolyte, puis d'une présentation des travaux de la littérature exploitant les charges aux interfaces pour la préconcentration de molécules biologiques dans des systèmes Micro-Nano-Micro (MNM) fluidiques. Ensuite, une deuxième partie est consacrée à la mesure du potentiel zeta par la méthode des courants d'écoulement. Nous y présentons l'amélioration du banc expérimental issu des travaux antérieurs à ma thèse, ainsi que le développement de nouveaux protocoles de préparation des surfaces permettant de rationaliser et de stabiliser les mesures. Une application à un détecteur original de molécules biologiques clos cette deuxième partie. Enfin, la troisième et dernière partie s'intéresse à la préconcentration de molécules biologiques. Une méthode originale de fabrication des dispositifs MNM et les résultats de préconcentration obtenus, très encourageants, sont décrits. Des premiers modèles numériques et phénoménologiques sont proposés, qui mettent en avant l'originalité de notre travail / The charges at liquid/solid interfaces are a key element for both understanding and exploiting the electrokinetic phenomena in micro/nanofluidics. The manuscript of my Ph.D thesis is dedicated to these phenomena, which is divided into three main parts: Above all, a simple overview of charges at the liquid/solid interface is proposed. Then, several common methods for measuring the zeta potential at the liquid/solid interface are described. Next, various effective methods to preconcentrate the biological molecules is presented with the help of the surface charges. Secondly, the streaming current, which is a standard method to measure the zeta potential in our laboratory, is detailed. It contains the upgrade of the experimental setup from the previous version and the development of new protocols, which improve dramatically the stabilization and the reproducibility of the measurements. In addition, an original biological sensor is briefly presented based on these advancements. Lastly, in the final part, we describe a method which is primitively utilised in the fabrication of Micro-Nano-Micro fluidic system. Based on this system, some favorable preconcentration results is obtained. Moreover, numerical simulations are presented to prove the originality of our work

[pt] Neste trabalho se analisam as características de colapso de um solo laterítico submetido à percolação de um licor cáustico a diferentes concentrações. O solo é uma areia quartzosa com uma pequena fração de finos cauliníticos. O licor é um efluente industrial, resultante da produção de alumínio, a base de soda cáustica. Mediante o presente estudo, determinou-se o efeito da infiltração do licor cáustico sobre três aspetos: colapsividade, transporte de solutos e características de sucção. Isto foi feito através de um programa experimental que incluiu ensaios de caracterização física-química do solo e do licor, ensaios edométricos, em edômetros especiais, para avaliar as características de colapso e de transporte de solutos, e ensaios de sucção pelo método do papel filtro. Os resultados do programa experimental mostraram que o solo é colapsível em presença de água, sendo sua colapsividade aumentada em presença do licor cáustico. Também indicaram que os parâmetros de transporte e sucção são fortemente afetados pela percolação do licor. A mudança destes parâmetros é função da concentração do licor. / [en] In this work, characteristics of collapse of a laterítico soil submitted to percolation of a caustic liqueur to different concentrations are analysed. The soil comprises a quartzitic sand with a small fraction of kaolinitic clay. The liqueur is a caustic fluid, from an aluminium industry. In the present study, effects of the caustic liqueur infiltration were observed considering three aspects: collapse, solute transport and soil suction characteristics. This was done through an experimental program that included physical and chemical characterization of the soil and liqueur, special oedometer tests to evaluate simultaneously collapse characteristics and solute transport, and suction tests using the filter paper method. The results of the experimental program showed that the soil suffers volume change in presence of water, and its colapsivity is increased in presence of the caustic liqueur. They also indicated that the transport and suction parameters are affected strongly by the percolation of the liqueur.