The aim of this work is to study the in-vitro aerodynamic performance of a new inhaled theophylline formulation prepared by supercritical fluids technique. For the analysis of the output from the in-vitro tests (and further in-vivo tests) a new, fast, sensitive high performance liquid chromatographic (HPLC) method was developed and validated for the determination of theophylline and other related derivatives in aqueous and urine samples using new packing materials (monolithic columns). These columns achieve efficient separation under lower backpressure and shorter time comparing to other traditionally or newly introduced C18 columns. Solution enhanced dispersion by supercritical fluid (SEDS) process has been applied for the production of anhydrous theophylline as pure crystals in the range 2-5 μm to be used as new inhaled dry powder formulation for asthma. Fifteen theophylline samples have been prepared under different experimental conditions. The drug produced by this method has been subject to a number of solid-phase analytical procedures designed to establish the crystal structure [X-ray powder diffraction (XRPD)], the structure and conformation [(FTIR), Fourier-transform Raman spectroscopy (FT-Raman)], and the morphology and particle size [scanning electron microscope (SEM)]. While, thermal gravimetric analysis (TGA), and differential scanning calorimetry (DSC) have been used to monitor any phase transition or polymorphic changes after processing. All these analytical techniques gave a satisfactory indication of the solid-state chemistry of the processed particles and assess the development of new inhalation product. The performance of inhaled SEDS theophylline with or without a carrier was evaluated using the developed HPLC method. Three samples having different particle sizes were selected out of the prepared powders by SEDS technique to be tested. The dose sampling unit and the Anderson Cascade Impactor were used to determine the in-vitro emitted dose and the deposition profiles of SEDS samples, respectively. The effect of different inhalation flows was studied using two different flows 28.3, and 60 L min-1 with 4 L inhalation volume. Different DPI devices were investigated in this study; Easyhaler® and Spinhaler®. The particle size has an important effect on the aerodynamic behaviour and deposition profile of inhaled drug, the smaller the particles the greater the total lung deposition. The presence of a carrier improves the respirable fraction for all the tested formulations.

The depletion of fossil fuels together with growing environmental concerns have created incitement for developing a more energy-efficient and environmentally-friendly vehicle fleet. The development towards cleaner heavy-duty vehicles started already in the 80’s with the introduction of emission legislations. Initially, engine optimization was enough for reaching the legislated levels of emissions. However, at present engine optimization is not enough but exhaust aftertreatment has become an essential part of heavy-duty vehicles, in order to meet the emission standards. Today, the total emissions are targeted which means that there is an interest in decreasing the idling emissions as well as the emissions during operation. To reduce the overall emissions several states in the USA have introduced idling legislations. Due to the limitations in idling time alternative solutions for power generation during rests are requested. A possible alternative is a fuel cell auxiliary power unit, combining a fuel cell with a fuel reformer (FC-APU).  The focus of this thesis is the development of the fuel reformer for an FC-APU, in which the hydrogen to the fuel cell is generated from diesel in a high-temperature catalytic process. The produced hydrogen can also be used in other heavy-duty vehicle applications i.e. selective catalytic reduction of NOx (HC-SCR), where addition of hydrogen is essential for reaching high conversion at low temperatures. The effect of using hydrogen from a fuel reformer in HC-SCR is included in this work. The catalytic material development is focused on developing promoted materials with lower rhodium content but with catalytic activity comparable to that of materials with higher rhodium content. This includes evaluation and extensive characterization of both fresh and aged promoted materials. The work also includes reactor design where a micro reactor with multiple air inlets is evaluated. This work has contributed to increased knowledge of catalytic materials suitable for reforming of diesel. By changing the support material from the traditionally used alumina to ceria-zirconia, increased H2 yield was achieved. In addition, the ceria-zirconia supported material was less prone to coke. By promoting the material with cobalt or lanthanum it was possible to decrease the rhodium content by 2/3 with enhanced catalytic performance. It was also discovered that promotion with lanthanum decreased the tendency for coking even further. Additionally, the lanthanum-promoted material had higher thermal stability as well as a stable highly dispersed rhodium phase. Furthermore, the work has contributed to an increased knowledge concerning the fuel reformer’s effect on HC-SCR. The work displays clear evidence of benefits with using hydrogen-rich gas from a fuel reformer instead of pure hydrogen. The benefits are derived from the content of low molecular weight hydrocarbons present in the hydrogen-rich gas, which are strong reducing agents increasing the NOx reduction. This finding proves that fuel reforming in combination with HC-SCR is a viable option for NOx abatement. / <p>QC 20150202</p>

No description available.

In this work, the steady-state performance of zeolite-based (Cu-ZSM-5) and vanadium-based honeycomb monolith catalysts was investigated in the selective catalytic reduction process (SCR) for NO removal using NH3. The aim was to delineate the effect of various parameters including pretreatment of the catalyst sample with H2, NH3-to-NO ratio, inlet oxygen concentration, and space velocity. The concentrations of the species (e.g. NO, NH3, and others) were determined using a Fourier Transform Infrared (FTIR) spectrometer. The temperature was varied from ambient (25 C) to 500 C. The investigation showed that all of the above parameters (except pre-treatment with H2) significantly affected the peak NO reduction, the temperature at which peak NO reduction occurred, and residual ammonia left at higher temperatures (also known as 'NH3 slip'). Depending upon the particular values of the parameters, a peak NO reduction of around 90% was obtained for both the catalysts. However, an accompanied generation of N2O and NO2 species was observed as well, being much higher for the vanadium-based catalyst than for the Cu-ZSM-5 catalyst. For both catalysts, the peak NO reduction decreased with an increase in space velocity, and did not change significantly with an increase in oxygen concentration. The temperatures at which peak NO reduction and complete NH3 removal occurred increased with an increase in space velocity but decreased with an increase in oxygen concentration. The presence of more ammonia at the inlet (i.e. higher NH3-to-NO ratio) improved the peak NO reduction but simultaneously resulted in an increase in residual ammonia. Pretreatment of the catalyst sample with H2 (performed only for the Cu-ZSM-5 catalyst) did not produce any perceivable difference in any of the results for the conditions of these experiments.

No description available.

<p>This dissertation seeks to bring together two philosophical literatures: the functions literature from the philosophy of biology, and the functionalist literature in naturalistic metaethics. Biological function suggests both objectivity and normativity: “the function of the heart is to pump blood” is an objective fact, and yet, hearts may malfunction—and malfunctioning is normative. Many ethicists wish to naturalize ethics—to help find a place for human normative lives in the objective natural world. In order to do so, they need tools to analyze humans as the products of evolutionary processes. Humans have a dual inheritance system involving both cultural and genetic inheritance that makes analysis of function for them particularly complex. In this dissertation, I develop a set of conceptual tools for those who wish to naturalize. I begin by developing an account of inheritance that can handle culture. Then, I elaborate the selected effects account of function so that it can handle all the evolutionary strangeness of culture. I then introduce the monolith fallacy—an error often committed by those studying human evolution—a tendency to oversimplify—to emphasize the high degree of complexity involved in any naturalizing project. Finally, I introduce the notion of value-guided functions—a kind of functioning not tied to our intentions, but to our values to round out the picture. I then apply the whole framework to the work of the functional metaethicists: Allan Gibbard, David Wong, Richard Joyce, and Philip Kitcher.</p> / Dissertation

Ce manuscrit est consacré à l’élaboration et à la photofonctionnalisation des monolithes de silice pour les techniques séparatives miniaturisées. La partie bibliographique situe d’abord l’intérêt des monolithes dans les techniques séparatives miniaturisées. L’état d’art sur l’utilisation des monolithes de silice dans ces techniques séparatives est ensuite établi en portant une attention particulière sur leur utilisation dans l’analyse d’échantillons biologiques et/ou environnementaux (préparation d’échantillons couplée aux méthodes séparatives ou utilisation de colonne de grande longueur). Un descriptif de la synthèse des monolithes de silice par le procédé sol gel est ensuite détaillé. Enfin, une étude des différentes méthodes de fonctionnalisation des monolithes de silice est présentée. L’optimisation des paramètres expérimentaux de la synthèse sol-gel a conduit à un procédé de synthèse robuste et répétable de capillaires monolithiques de silice de grandes longueurs et d’efficacités élevées (efficacités de l’ordre de 160 000-200 000 plateaux/m). Le travail expérimental s’est ensuite orienté sur l’optimisation de procédés de fonctionnalisation par voie thermique et sur le développement de nouveaux procédés de photopolymérisation ou de photografting par « photo click chemistry ». Les résultats obtenus dans des modes chromatographiques variés après photofonctionnalisation avec différents monomères montrent que ces procédés sont polyvalents et qu’un contrôle des paramètres permet de conserver les performances chromatographiques du matériau de départ. Outre sa simplicité et sa rapidité, cette approche permet de définir et de localiser différentes chimies de surface au sein d’une même colonne. Cette spécificité a été mise à profit pour le couplage en ligne dans une colonne de nanochromatographie, d’une étape de préconcentration avec une étape de séparation de neuropeptides modèles / This manuscript is dedicated to the development and functionalization of monolithic silica stationary phases for miniaturized separation techniques. The bibliographic section first summarizes the interest of monolithic phases for the development of miniaturized separation techniques and their advantages over their particulate counterparts (small particles or core shell ones). The state of the art on the use of silica monolithic columns in separation techniques is then established, with a focus on their use in the analysis of biological and/or environmental samples (coupling sample preparation with an analysis method or using long columns). Then a detailed description of the sol gel synthesis of monolithic silica is presented. Finally, a study of different established methods of functionalization of silica monoliths is presented and the potential of photofunctionalization is highlighted for the rapid and homogeneous in-situ functionalization of monolithic capillaries. The experimental part focuses first on the development and optimization of a robust process of synthesis of monolithic silica capillary columns (efficiencies around 160 000-200 000 plates/m). The work is then focused on the improvement of classical functionnalization processes and on the development of new photofunctionalization ways (photopolymerization and photo click chemistry) of silica monolithic columns. The results obtained after photofonctionnalisation in various chromatographic modes (from ion exchange to reversed phase and HILIC) mode with different monomers show that these methods are versatile and that the control of the parameters allows keeping the chromatographic performances of the starting material. Besides its simplicity and speed, this approach allows to define and to locate different surface chemistries in the same column. This specificity has been exploited to the in-line coupling a preconcentration step with a separation step in a single column, for the separation of model neuropeptides

Ce manuscrit est consacré à la synthèse par procédé sol-gel et à la caractérisation de matériaux monolithiques de silice hybrides pour les techniques séparatives miniaturisées : nano-chromatographie en phase liquide (nano-CPL), électrochromatographie capillaire (ECC) et microsystèmes séparatifs. La partie bibliographique situe les axes de développement récents des techniques séparatives : l’augmentation de l’efficacité par unité de temps, l’augmentation de la capacité de pics et la miniaturisation de ces techniques. Après un descriptif détaillé de l’évolution des techniques séparatives lors de ces dernières années, une attention particulière est portée sur les phases stationnaires monolithiques à base de silice. Enfin, une étude approfondie des différentes fonctionnalisations de ces monolithes de silice met en évidence l’intérêt porté aux monolithes de silice hybrides en termes de simplification du protocole de synthèse. La partie expérimentale est ainsi axée sur le développement et la caractérisation de ces monolithes de silice hybrides dédiés à la chromatographie à polarités de phases inversée. Dans un premier temps, la synthèse de monolithes de silice hybrides C3 illustre la possibilité de synthétiser par voie sol-gel (100% aqueux) un monolithe de silice fonctionnalisé et performant en une seule étape (« one pot »). Dans un second temps, ce type de procédé est employé et optimisé afin de synthétiser des capillaires monolithiques de silice hybrides C8 présentant des performances équivalentes à leurs homologues C8 préparés en deux étapes (synthèse puis greffage) et comparables à des colonnes particulaires (d particules 5 μm) / This manuscript is dedicated to the synthesis (via sol-gel process) and caracterization of hybrid monolithic silica for miniaturized separation techniques : nano-liquid chromatography (nano-LC), capillary electrochromatography (CEC) and microchips. The bibliography part deals with the recent axis of development of these separatives techniques : increase of efficiency per time unit, increase of peak capacity and miniaturisation of these techniques. After an overview of this evolution, the manuscript is focused on the silica monolithic stationnary phases. Finally, a detailed study on the different kinds of protocol fonctionnalization of these silica monoliths highlights the advantage of simplifying the synthesis using a single step protocol (« one pot »). The experimental part is also focused on this kind of single step protocol so as to synthesize hybrid silica monoliths dedicated to the reversed phase mode in chromatography. First, the synthesis of hybrid C3 silica monoliths shows the ability to synthesize a functionnalized silica monolith via a single step sol gel process (« one pot »). Then, this kind of process is used and optimized in order to synthesize a hybrid C8 silica monolithic into capillaries. These stationary phases allowed reaching performances similar to those synthesized in two steps (sol-gel process and grafting) and to the particulate columns (5 μm).

Les matériaux polymères ont connu un engouement considérable avec l’avènement de l’ère du pétrole et connaissent aujourd’hui encore un succès considérable notamment au travers de la valorisation de ressources naturelles mais également d’applications spécifiques à haute valeur ajoutée, liées à des domaines aussi divers que la chimie analytique, l’exploration spatiale, la médecine où l’enjeu premier est souvent la conception d’objet miniaturisés. Dans ce travail de thèse nous avons développé des matériaux polymères à taille micrométrique, immobilisés soit dans des microcanaux (diamètre interne = 75 µm) ou à la surface de substrats de verre (épaisseur de quelques centaines de µm). Une morphologie de type monolithique a été choisie afin de conférer auxdits matériaux des propriétés de perméabilité, résistance mécanique et thermique compatibles avec des applications dans le domaine de la chimie en flux. Afin de contrôler les propriétés d’interaction aux interfaces des matériaux, un monolithe générique, présentant des unités ester de N-hydroxysuccinimide en surface, a été préparé et fonctionnalisé à façon. Ainsi ont été immobilisés des segments moléculaires jouant le rôle de sélecteurs – pour des applications en électrochromatographie – ou de ligands de nanoparticules métalliques – pour applications en catalyse supportée – via des méthodes classiques (substituion nucléophile) ou originales (photo-addition radicalaire thiol-ène) de greffage.Les matériaux ont été caractérisés par une combinaison de méthodes spectroscopiques, microscopiques, de diffraction, de thermogravimétrie permettant de corréler les propriétés électrochromatographiques ou catalytiques avec la structure interfaciale des matériaux monolithiques. A titre d’exemples d’application, nous pouvons citer la séparation électrochromatographiques de molécules toxiques tels les polluants organiques (aniline, phénols, hydrocarbures aromatiques polycycliques, polychlorobiphényles) et les conservateurs pour les crèmes cosmétiques (parabènes), de biomarqueurs (hydrocarbures aromatiques polycycliques, bases pyrimidiques). Ces analyses ont été réalisées avec des solutions modèles de laboratoire mais aussi des matrices réelles (crèmes cosmétiques, analogues d’échantillons extraterrestres). Aussi les réactions catalytiques de réduction de nitroarènes, d’oxydation d’alcool aromatique, de couplage carbone-carbone et la détection par spectroscopie Raman exaltée de surface de pesticides (trifuraline) et d’intermédiaires de synthèse (para-nitrophénol) ont été réalisées / Polymeric materials have gained immense popularity with the golden age of petroleum and they still today meet with great success through Green polymer chemistry approaches and numerous high added value dedicated application in scientific domains such as analytical chemistry, medicine, space investigations, where one of the key for success is the design of miniaturized objects. In this contribution, micro-sized monolithic materials have been designed though either in microchannel immobilization (I.D. = 75 µm) or surface attachment on glass substrates (hundredths of microns in thickness). Polymers exhibiting monolithic morphology were considered to benefit of high permeability, mechanical and thermal resistances which are mandatory to flow chemistry applications. With the aim to control the interfacial interaction ability, a generic monolith having N-hydroxysuccinimide ester groups was used and on purpose functionalized. Molecular segments acting as selector – for electrochromatographic applications – of metal nanoparticles ligands – for supported catalysis applications – have been immobilized on the monolith surface via classical (nucleophilic substitution) or original (photo-induced thiol-ene click) grafting reactions.The so-designed materials were characterized through spectroscopic, microscopic, diffraction, thermogravimetric methods providing insight into correlation between the observed separation and catalytic abilities and the interfacial structure of the monolith. As representative examples of application, one may cite the electrochromatographic separation of toxic molecules such as organic pollutants (phenols, anilines, polycyclic aromatic hydrocarbons, polychlorobiphenyls), preservatives in cosmetics (parabens) and biomarkers (polycyclic aromatic hydrocarbons, pyrimidic bases). The analyses were conducted on model solutions and complex matrices (cosmetics, extraterrestrial analog samples). Flow catalytic reaction meant for the reduction of nitroarenes, the oxidation of aromatic alcohol, the carbon-carbon coupling and the sensitive detection of pesticides and synthesis intermediates (para-nitrophenol) have been achieved

Les laboratoires sur puce sont des dispositifs miniaturisés qui offrent la possibilité d'intégrer en ligne toutes les étapes de la chaîne analytique tout en réduisant les volumes d’échantillon et les temps d’analyse. Ainsi, ils constituent potentiellement un outil de diagnostic particulièrement adapté pour l’analyse de biomarqueurs phosphorylés, pour lesquels une préconcentration est nécessaire en raison de leur faible abondance dans les fluides biologiques. C’est pourquoi, de nouvelles méthodes, dédiées à l'enrichissement de phosphopeptides, ont été développées ces dernières années et en particulier celles utilisant des supports solides basées sur la chromatographie d’affinité sur des ions métalliques immobilisés (IMAC). Parmi les supports solides intégrables en microsystème, les monolithes organiques constituent une option privilégiée grâce à la possibilité d’être synthétisés in situ. Le but de ce travail de thèse était donc de développer un laboratoire sur puce intégrant une préconcentration des phosphopeptides sur support monolithique basé sur le principe de l’IMAC et leur séparation électrophorétique en ligne.Dans un premier temps, nous avons développé deux approches innovantes qui ont permis de synthétiser pour la première fois un monolithe à base d’éthylène glycol méthacrylate phosphate (EGMP) et de bisacrylamide (BAA) par voie photochimique dans des microsystèmes. La première stratégie développée dans des puces en verre repose sur la synthèse du monolithe à l’aide d’un microscope à épifluorescence. La deuxième approche est basée sur les propriétés photochimiques d’un nouvel amorceur qui a permis de synthétiser et d’ancrer le monolithe, en une seule étape, aux parois des puces en polydiméthylsiloxane (PDMS). Une caractérisation de ce monolithe en termes de morphologie, de perméabilité, de porosité et de surface spécifique a ensuite été réalisée. Ceci a permis de démontrer le potentiel de ce monolithe pour la préconcentration.Dans un deuxième temps, une méthode de séparation par électrophorèse couplée à une détection par fluorescence a été développée sur puce en verre. Celle-ci a permis de séparer un mélange de phosphopeptides modèles fluorescents possédant différents sites et degrés de phosphorylation. Les phosphopeptides ont été détectés en moins de 2 min avec une excellente résolution (R>3) et une bonne efficacité (plateaux théoriques compris entre 11000 et 25000). Enfin, le couplage en ligne du module de préconcentration monolithique et de séparation/détection a été réalisé. Sur ce dispositif miniaturisé, une préconcentration basée sur l’IMAC-Zr4+ a ainsi été développée. L’efficacité de la capture et de l’élution des phosphopeptides a été démontrée et des facteurs de préconcentration supérieurs à 340 ont été obtenus. En conclusion, ce laboratoire sur puce ouvre des perspectives très prometteuses dans le domaine du diagnostic de pathologies dont le processus physiopathologique implique des phosphopeptides.Mots clés : laboratoire sur puce, microsystème, phosphopeptide, IMAC, monolithe, photopolymérisation, préconcentration, électrophorèse sur puce / A lab on-a-chip is a miniaturized device that integrates onto a single chip different analytical steps (preconcentration, separation, detection...) with minimal sample consumption and short analysis time. They are potentially beneficial in phosphorylated biomarker analysis for which a preconcentration step is necessary because of their low abundance in biological fluids. That's why selective enrichment methods of phosphopeptides have been developed in recent years in particular those based on solid supports like Immobilized Metal Affinity Chromatography (IMAC). Among the solid supports, organic polymer monoliths present practical advantages when used in microchips due to their ease of preparation and in situ polymerization. The aim of this work was to develop a lab-on-a-chip integrating a monolithic support for online IMAC-based preconcentration and electrophoretic separation of phosphopeptides.In the first part, we developed two innovative approaches which allowed us to synthesize, for the first time, an ethylene glycol methacrylate phosphate-co-bisacrylamide (poly (EGMP-co-BAA)) monolith by a photo-driven process in microsystems. The first monolith synthesis approach was developed in glass microchannels using an inverted epifluorescence microscope as UV-irradiation source. The second approach was based on the photochemical properties of a new initiator which allowed the simultaneous synthesis and anchorage of the monolith in native polydimethylsiloxane (PDMS) microchips. A characterization (morphology, permeability, porosity and specific surface area) of (poly (EGMP-co-BAA)) monolith was then performed which demonstrated the potential of this monolith for preconcentration.Then a glass microchip electrophoresis method coupled to a detection by fluorescence was developed to separate a mixture of phosphopeptides fluorescent models differing with the position and number of phosphorylation sites. The phosphopeptides were detected in less than 2 min with excellent resolution (R> 3) and good efficiencies ranging from 11000 to 25000 plates. Finally, an integrated microdevice was developed by combining online preconcentration based on IMAC-Zr4+ and separation/detection of phosphopeptides. The performance of this integrated microdevice to capture and to elute the phosphopeptides was demonstrated and signal enhancement factors (SEF) higher than 340 were obtained. This lab-on-a-chip device opens news perspectives for phosphoproteomic applications and the diagnostic of diseases where the pathophysiological process involves phosphopeptides