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 ¿m 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. / Egyptian Ministry of Higher Education

This thesis deals with the preparation of materials for use in separation science and their surface modification by grafting. The overall aim is the preparation of diverse materials by combination of a set of developed tools. Included in the thesis is the synthesis of monolithic media using non-traditional crosslinkers, the characterization of their porous properties and initial testing in reversed-phase chromatographic separation of proteins. The preparation of a library of short polymer chains, telomers, with varied functionality and their characterization is reported. Included in the characterization is the gradient polymer elution chromatography of selected telomers on a monolithic column in capillary format. The technique shows promise as a tool for monitoring of polymerization processes and for the separation of telomers with similar size but different functionalities or characteristics. Finally, the combination of polymeric support materials and the prepared telomer library is used in surface modification. Surface modification is performed onto activated surfaces via a “grafting to” approach. One example is shown, the surface modification of epoxy-modified divinylbenzene particles by attachment of telomer chains introducing ion-exchange functionality. The material is tested for the separation of proteins, in ion-exchange chromatography mode.

No description available.

Inorganic porous materials are widely used in a number of applications, where is a need to functionalize and produce materials with a multiscale porosity. The first part of the thesis describes how a novel and facile powder processing approach, using pulsed current processing (PCP) or, as it is commonly called, spark plasma sintering (SPS), has been employed to produce mechanically stable, hierarchically porous bodies from different porous powders. Surfactant-templated mesoporous spheres were PCP-treated to yield meso/macro porous monoliths. The bimodal pore size can be tailored by choice of templating molecules in the aerosol-assisted synthesis process and by the particle size of the spheres. Diatomite powders were used to produce macro/macroporous monoliths. The densification behaviour of this inexpensive and renewable macroporous raw material was evaluated in detail, and an optimum temperature range was identified where the PCP process yields mechanically strong monoliths. Binder-less, hierarchically porous zeolite monoliths were produced from various zeolite powders, e.g. silicalite-1, ZSM-5 and zeolite Y. Line-broadening analysis of X-ray powder diffraction data by the Rietveld method and electron microscopy showed that the formation of strong interparticle bonds during the PCP process is associated with a local amorphization reaction that is induced by the high contact stress and temperature. Xylene isomerisation studies showed that binder-less ZSM-5 monoliths display a high catalytic selectivity. Direct (in-situ) nanoparticle functionalization of surfactant templated mesoporous silica particles has also been demonstrated. Pre-synthesized TiO2 nanoparticles were dispersed in a precursor solution, containing surfactant and silica source, and processed in an aerosol-generator to produce spherical nanoparticle-functionalized mesoporous particles.

High performance liquid chromatography (HPLC) is one of the major techniques in separat-ion sciences. Faster separation and higher efficiency are required to meet ever-growing demands. Despite numerous studies and achievements on improving mass transfer in particulate packings discontinuity seems to be the cornerstone drawback in their development. Macroporous continuous beds or monoliths are therefore a promising alternative to the particle medium. This thesis deals with preparation of new monoliths used as carrier for HPLC. Two different approaches were developed for two polymer systems. One was based on polycondensation of epoxy resins and polyamines which were components of an oil-in-water emulsion. An epoxy resin mixture was dispersed in aqueous polyamine phase with the aid of a surfactant. The other involved a traverse of a ready-made polymer solution around its upper critical solution temperature (UCST). In other words, linear polyamides, non-covalently crosslinked polymers, dissolved in a solvent at temperature higher than their UCST followed by slow cooling to below the critical temperature to precipitate the polymers. Partly re-established hydrogen bonds resulted in the formation of crystallites that interconnected into a network structure. Factors controlling morphology and porosity of final products were investigated. The study also deals with surface modifying for chromatographic applications. Functionalization pathways attempted in the thesis were quaterization of inherent amine of the epoxy-based monoliths and grafting tentacle ion groups via glycidyl methacrylate by atom transfer radical polymerization (ATRP) for ion exchange chromatography (IEC).

This thesis focuses on my endeavors to prepare new porous polymeric monoliths that are viable to use as supports in flow-through processes. Polymer monoliths of various porous properties and different chemical properties have been prepared utilizing the thermally induced phase separation (TIPS) phenomenon and step-growth polymerization reactions. The aim has been to find appropriate synthesis routes to produce separation supports with fully controlled chemical, physical and surface properties. This thesis includes preparation of porous monolithic materials from several non-cross-linked commodity polymers and engineering plastics by dissolution/precipitation process (i.e. TIPS). Elevated temperatures, above the upper critical solution temperature (UCST), were used to dissolve the polymers in appropriate solvents that only dissolve the polymers above this critical temperature. After dissolution, the homogeneous and clear polymer-solvent solution is thermally quenched by cooling. A porous material, of three dimensional structure, is then obtained as the temperature crosses the UCST. More than 20 organic solvents were tested to find the most compatible one that can dissolve the polymer above the UCST and precipitate it back when the temperature is lowered. The effect of using a mixture of two solvents or additives (co-porogenic polymer or surfactant) in the polymer dissolution/precipitation process have been studied more in depth for poly(vinylidine difluoride) (PVDF) polymers of two different molecular weight grades. Monolithic materials showing different pore characteristics could be obtained by varying the composition of the PVDF-solvent mixture during the dissolute­ion/precipitation process. Step-growth polymerization (often called polycondensat­ion reaction) combined with sol-gel process with the aid of porogenic polymer and block copolymer surfactant have also been used as a new route of synthesis for production of porous melamine-formaldehyde (MF) monoliths. In general, the meso- and macro-porous support materials, for which the synthesis/preparation is discussed in this thesis, are useful to a wide variety of applications in separation science and heterogeneous reactions (catalysis).

Les réacteurs structurés de type monolithe apparaissent comme une alternative intéressante aux réacteurs triphasiques conventionnels (à lit fixe ruisselant ou à suspension), car ils offrent dans leurs canaux millimétriques, dans une large gamme de débits, un écoulement bien défini, consistant en une succession de bulles et bouchons liquides (écoulement dit de Taylor). Celui-ci, proche de l'écoulement idéal " piston ", permet également une intensification du transfert gaz-liquide, notamment grâce à l'existence d'un film mince de liquide séparant les bulles de la paroi catalytique. Par ailleurs, les dernières technologies de fabrication additive offrent de nouvelles possibilités de réalisation de ce type de réacteur, sous la forme d'une structure métallique conductrice alternant canaux catalytiques et canaux dédiés au fluide caloporteur. Cette configuration efficace de réacteur-échangeur autorise à considérer le monolithe comme uniforme en température et à réduire sa modélisation à celle d'un canal unique isotherme. C'est la stratégie de modélisation adoptée dans ce travail de thèse, qui cherche à représenter chacun des phénomènes avec seulement le niveau de complexité nécessaire, en progressant de l'échelle locale à l'échelle du réacteur. L'outil choisi ici est le logiciel COMSOL Multiphysics pour sa capacité à traiter des problèmes multi-physiques et multi-échelles. Une approche classique pour les écoulements de Taylor est appliquée, construite autour d'une " cellule unitaire " qui se déplace à la vitesse diphasique le long du canal. Le champ hydrodynamique calculé sert alors de support au calcul du transfert de masse entre les phases. Le premier cas d'étude traité - transfert d'oxygène dans l'eau avec réaction de consommation de l'oxygène en paroi - sert à poser les bases du modèle, en examinant le bien-fondé de différentes hypothèses simplificatrices, concernant le nombre de phases modélisées, les conditions aux limites du domaine pour les équations résolues, ou encore la forme de bulle. Ce travail préliminaire a montré que la résolution de la phase liquide uniquement, autour d'une bulle de forme simplifiée, peut assurer une représentation satisfaisante des profils de vitesse dans les bouchons et dans le film de lubrification par rapport à des calculs diphasiques. Il a aussi permis d'évaluer de façon séparée les contributions au transfert gaz-liquide de chacune des zones d'interface (film, nez ou arrière de la bulle) et de quantifier l'influence sur l'efficacité du transfert de la fréquence de bullage, qui modifie à la fois l'aire interfaciale et l'intensité de recirculation dans les bouchons. La démarche est ensuite appliquée au cas de l'hydrogénation de l'alpha-pinène, et validée par une campagne d'essais réalisés pour un tube catalytique de 2 mm de diamètre et de 40 cm de longueur, fonctionnant sous 21 bar et entre 100°C et 160°C. Le modèle utilise pour la couche catalytique en paroi une loi cinétique intrinsèque, identifiée en réacteur autoclave agité (pour le même catalyseur de Pd/Al2O3, mais sous forme de poudre). Il suit par un calcul instationnaire la progression de la cellule unitaire jusqu'à la sortie du réacteur. Outre les effets des paramètres clés mis en évidence précédemment, ceux de la consommation de gaz le long du réacteur et des conditions " initiales " de saturation du liquide sont examinés. Le fonctionnement du monolithe peut être reproduit dans son intégralité à partir de ce modèle, par association de canaux recevant des débits individuels de gaz et de liquide représentatifs de la distribution des fluides observée expérimentalement, et en lui incorporant un module de mélange des fluides issus de chacun des canaux en sortie de réacteur. Ce modèle sert aussi de référence pour l'évaluation d'un outil de dimensionnement plus direct, basé sur une hydrodynamique simplifiée et des coefficients d'échange globaux évalués à partir de corrélations ou des simulations numériques dédiées. / Structured reactors of monolith type arise as an interesting alternative to conventional three-phase reactors (trickle-bed or slurry reactors), because they offer, in a wide range of flow rates, a welldefined flow structure in their millimetric channels, consisting of an intermittent series of gas bubbles and liquid slugs (i.e. Taylor flow). This flow regime, close to the ideal “plug flow” behavior, enables the improvement of gas-liquid mass transfer, thanks to the thin liquid film laying between the bubbles and the catalytic wall. Moreover, recent additive manufacturing technologies offer new possibilities for producing such a reactor, in the form of a metal heat-conducting block alternating catalytic channels and channels dedicated to the coolant. This efficient reactor/heat exchanger configuration allows the monolith to be considered as uniform in temperature and to reduce its modeling to that of a single isothermal channel. This is the modeling strategy adopted in this thesis, which aims to represent each phenomenon with the required level of complexity only, progressing from the bubble/slug scale to the reactor scale. COMSOL Multiphysics® software is selected as the numerical tool for its ability to handle multiphysics and multi-scale problems. The approach classically used for Taylor flows is applied, based upon a "unit cell" (gas bubble associated to a lubricating liquid film and two liquid half-slugs) that travels along the channel at the two-phase velocity. Solved hydrodynamics then serves as a basis for the calculation of gas-liquid mass transfer. The first study case - oxygen transfer into water with consumption at the channel wall – lays the foundations of the model, by examining the merits of various simplifying hypotheses concerning the number of phases to be considered (gas and liquid, or liquid only), the boundary conditions for the solved equations (periodicity, slip conditions at the gas-liquid interface), or the bubble shape (calculated or "simplified"). This preliminary work has shown that the simplest approach, which consists in solving the liquid phase only, as flowing around a bubble of simplified shape, can ensure a satisfactory representation of the velocity profiles in the liquid slugs and in the lubrication film, compared with two-phase flow (semi-analytical or CFD) calculations. This study also allows to evaluate separate contributions from different parts of the bubble surface (film, and front or back cap) to gas-liquid mass transfer, and to quantify the influence on transfer efficiency of bubble frequency, which affects both the interfacial area and the recirculation intensity in the slugs. The modelling approach is then applied to the hydrogenation of alpha-pinene and validated by an experimental tests carried out in a catalytic tube of 2 mm diameter and 40 cm length, operating at 20 bar and between 100°C and 160°C. The model uses an intrinsic kinetic law for the reaction occurring in the catalytic washcoat, identified in a stirred autoclave reactor (for the same Pd/Al2O3 catalyst, but in powdered form). Transient calculation follows the progression of the unit cell until the reactor exit. In addition to the effects of the key parameters previously identified, those of gas consumption along the reactor (hydrogen being here the limiting reactant) and "initial" saturation conditions of the liquid are examined. The behavior of the entire monolith can be mimicked from this model by combining, in a mixing module, the outflows of channels whose individual gas and liquid flow rates match a measured fluid distribution. This model also serves as a reference for evaluating a more direct reactor sizing tool, based on simplified hydrodynamics and overall exchange coefficients evaluated from correlations or dedicated numerical simulations.

Ce manuscrit est consacré à l’élaboration de phases monolithiques à base de dioxyde de titane pour les techniques séparatives appliquées à l’analyse des produits phosphorylés. La partie bibliographique situe d’abord l’intérêt des monolithes pour le développement des techniques séparatives en portant une attention particulière à la problématique de miniaturisation. L’état de l’art sur l’utilisation du dioxyde de titane, dans les sciences séparatives, est ensuite établi. À ce niveau, les principales caractéristiques physico-chimiques et chromatographiques de ce matériau sont revues pour les lits particulaires. Un descriptif de la synthèse des monolithes de dioxyde de titane par le procédé sol-gel est ensuite détaillé avant d’illustrer la mise en oeuvre de ce type de colonnes dans les techniques séparatives. La partie expérimentale est axée d’abord sur la compréhension du comportement du dioxyde de titane particulaire en chromatographie liquide à interaction hydrophile (HILIC). Le travail expérimental est ensuite orienté vers l’élaboration d’un procédé sol-gel répétable, permettant d’obtenir le matériau sous le format monolithique. Dans un premier temps, le support est élaboré sous forme de barreau, dont l’utilisation potentielle après mise en colonne est illustrée dans le cadre de la purification et de l’enrichissement des acides aminés phosphorylés. Des adaptations de protocole sont apportées pour la synthèse in situ de ces monolithes à l’intérieur des capillaires afin de répondre aux contraintes des techniques séparatives miniaturisées. Ces monolithes sont caractérisés en HILIC, par comparaison avec les phases particulaires. Pour terminer, les propriétés chromatographiques originales de ces phases sont mises à profit pour la séparation et le traitement d’échantillons, contenant des produits phosphorylés / This manuscript is dedicated to the development of monolithic titania phases for chromatographic analysis of phosphorylated compounds. The bibliography section first summarizes the interest of monolithic phases for the development of separation techniques while emphasizing on the problem of miniaturization. The state of the art on the use of titanium dioxide in liquid chromatography techniques is established. In this subject, the physico-chemical and chromatographic behaviour of this material are reviewed for particle beds. Then a detailed description of the sol-gel synthesis of monolithic titania is presented with a final illustration of the potential use of this support in separation techniques. The experimental part concentrates first on the analysis of the chromatographic behaviour of particulate titania in the hydrophilic interaction mode (HILIC). The work is then focused on the development of a repeatable sol-gel process that enables the formation of monolithic titania. The monolithic phase is first synthesized at a large scale, and its potential use, after column cladding, is illustrated with the purification and enrichment of phosphorylated amino acids. The elaboration process is also adapted to meet with the miniaturized separation techniques by performing an in situ synthesis route within capillary columns. These columns are characterized in HILIC by comparison with the chromatographic properties observed for titania particulate beds. The original behaviour of native titania observed also for the synthesized monolithic phases is finally applied to the separation and sample treatment of mixtures of phosphorylated products

Considerable research is being carried out into the parameters that affect catalyst performance in order to meet the latest emission regulations. The conversion efficiency and the durability of automotive catalytic converters are significantly dependent on catalyst flow performance. Related investigations are commonly conducted using CFD techniques which represent an inexpensive and fast alternative to experimental methods. This thesis focuses on the flow performance of automotive catalytic converters using both experimental and computational techniques. The work describes the effects of inlet flow conditions on catalyst performance, the application of radial vanes to catalyst systems and the refinement of the CFD flow model which increases the accuracy of the predicted catalyst flow performance. the effects of inlet flow conditions on the flow maldistribution across the catalyst face and the total pressure loss through the system were assessed using a steady air flow rig. Tests were conducted over a range of Reynolds numbers typically encountered in automotive catalytic converters using a uniform and a fully-developed inlet flow condition. The results showed that the flow maldistribution significantly increases with Reynolds number notably in wide-angled diffusers. The catalyst flow performance is considerably improved when the inlet flow is uniform rather than fully-developed, the non-dimensional total pressure loss is reduced by 8% at Re=60000 and the flow maldistribution across the catalyst face is decreased by 12.5% and 15% respective Reynolds numbers of 30000 and 60000 when using a 60 degree diffuser. The total pressure loss through the system was found to be mostly associated with the monolith brick resistance. When the flow maldistribution is approximately 2, the pressure loss across the monolith brick represents 80% of the system pressure loss. The flow maldistribution across the catalyst face was improved by locating a system of radial splitters in the diffuser. The optimum flow performance was found to be a complex function of the vane design. A maximum improvement in the flow maldistrution indices M and Mi of 25% and 50% respectively was achieved at the expense of an increase in total pressure loss of 13.5% at Re = 60000. Both CFD and flow visualisation techniques were used as an aid to interpreting the flow field in the diffuser. Although a qualitative agreement was obtained using CFD, the flow maldistribution across the catalyst face was underpredected by up to 20%. The accuracy of the flow predictions was significantly improved by investigating the flow field in the monolith channels. Flow recirculation occurs in the channel entry length when the flow approaches the monolith channels at an angle which induces an additional implemented into four models of the flow through axisymmetric catalyst assemblies using various diffuser geometries and inlet flow conditions. By including the flow entrance effects in the porous media approach, the flow maldistribution was predicted within 8% instead of 15% when these effects are neglected. Further investigation of the flow in the monolith channels will be required to accurately model three-dimentional flows (racetrack catalysts) and to include various channel geometries and system flow rates.

Microfluidics miniaturizes many benchtop processes and provides advantages of low cost, reduced reagent usage, process integration, and faster analyses. Microfluidic devices have been fabricated from a wide variety of materials and methods for many applications. This dissertation describes four such examples, each employing different features and fabrication methods or materials in order to achieve their respective goals. In the first example of microfluidic applications in this dissertation, thermoplastics are hot embossed to form t-shaped channels for microchip electrophoresis. These devices are used to separate six preterm birth (PTB) biomarkers and establish a limit of detection for each. The next chapter describes 3D printed devices with reversed-phase monoliths for solid-phase extraction and on-chip fluorescent labeling of PTB biomarkers. I demonstrate the optimization of the monolith and selective retention of nine PTB biomarkers, the first microchip study to perform an analysis on this entire panel. The third project describes the iterative design and fabrication of glass/polydimethylsiloxane (PDMS) devices with gold and nickel electrodes for the self-assembly of DNA nanotubes for site-selective placement of nanowires. Simple flow channels and “patch electrode” devices were successfully used, and DNA seeding was achieved on gold electrodes. Finally, a 3D printed device for cancer drug screening was developed as a replacement for one previously fabricated in PDMS. Devices of increasing complexity were fabricated, and those tested found to give good control over fluid flow for multiple inlets and valves. Although the applications and methods of these projects are varied, the work in this dissertation demonstrates the potential of microfluidics in several fields, particularly for diagnostics, therapeutics, and nanoelectronics. Furthermore, it demonstrates the importance of applying appropriate tools to each problem to gain specific advantages. Each of the described devices has the potential for increased complexity and integration, which further emphasizes the advantages of miniaturized analyses and the potential for microfluidics for analytical testing in years to come.