A major challenge facing the global health community is the production of thermally stable vaccines that eliminate the need for unfavorable cold-chain storage protocols, which often require temperatures as low as -80°C. Spray drying is a promising technique to produce thermally stable vaccine powders that retain their efficacy when stored at ambient conditions. Spray drying is gaining popularity in the pharmaceutical community due to its scalability, low cost and high throughput. Processing by spray drying can rapidly immobilize the active vaccine ingredient, such as a viral vector, in an amorphous glassy matrix of a stabilizing excipient tailored to the biologic being stabilized. This encapsulation and reduction in mobility keeps the biologic isolated from mechanical, thermal or chemical stresses that cause damage and inactivation. However, choosing the best excipient, or excipient blend, and optimizing the formulation are costly and time-consuming processes and furthermore, the effects of spray drying on viral vector activity are not fully understood. This thesis focuses on modelling the processing environment for preparing such vaccine powders, by both experimental and numerical means, to understand the relevance of mechanical, thermal and chemical stresses on viral vector activity. Specifically, the viral vector studied here was human type 5 adenovirus (AdHu5), with intended use in tuberculosis vaccines. Mechanical stresses associated with the shear inside the nozzle of a spray dryer were experimentally studied. Viral activity losses associated with shear stresses in an atomizing nozzle were attributed to aggregation; aggregation was created by damaging the virus at very high mechanical stresses but most aggregation was attributed to dispersing the virus in the excipient solution. It was concluded that overall, mechanical stresses in the nozzle caused a minimal amount of viral activity loss compared to other processing factors during spray drying, and in fact, could have a positive influence at moderate shear rates since it actually caused the break-up of AdHu5 aggregates. To investigate thermo-chemical stresses, it was necessary to demonstrate that acoustic levitation of a single drying droplet was an effective screening method to select promising excipients for spray dried vaccines, and could be used to experimentally validate a numerical model of droplet drying. For several different sets of binary carbohydrate blends, levitated particles were found to match property and activity trends seen in spray dried powders when the surrounding temperature of the levitator matched the outlet temperature of the spray dryer. The numerical droplet drying model could predict drying time, particle size, and component distribution within a final dried particle; the component distribution was used to aid in spatially locating the viral vector which was shown to be related to vaccine thermal stability. The model predictions associated with virus location in a dried particle were confirmed experimentally using coated silica nanoparticles as virus analogues, and several different molecular weight dextrans in the mannitol/dextran blend in order to change the location of the virus. Overall, this work provides a deeper understanding of how spray drying can be used to produce thermally stable vaccine powders, and the arising guidance can be applied to improve formulation development based on the end targets and applications. Shear stress was found to be a negligible source of viral vector activity loss, and the application of heat to the acoustic levitator was found to create drying conditions that allowed the levitator to create materials that mimicked the properties of spray dried powders. Finally, a numerical model was validated experimentally, with both modelled predictions and confocal laser scanning microscopy confirming that an increase in dextran molecular weight in formulations caused a decrease in viral vector and silica nanoparticles at the air-solid interface. The knowledge gained by using screening methods and mathematical models of the spray drying process can reduce the time and cost inputs of vaccine development by identifying promising excipients with minimal experimentation. / Thesis / Doctor of Philosophy (PhD) / To retain their effectiveness, most mass-market vaccines must be stored in refrigerated or frozen conditions but the specialized equipment associated with such storage limits the success of administration programs. Creating dry powder vaccines that can be stored at room temperature is an efficient method to limit liquid vaccine wastage caused by exposure to warmer temperatures. This is achieved by combining the active ingredient with protective stabilizing materials and drying the solution into a powder using spray drying. However, identifying and developing effective dry powder products is costly and time-consuming. This research aims to reduce the costs associated with vaccine development by using other drying methods to identify potential protective sugars without the need for large-scale experiments, as well as by using mathematical models to predict the outcomes of the drying process. The effect of various stresses during the drying process on the active vaccine ingredient are evaluated to improve the effectiveness of the final dry product. Overall, the ability to produce stable dry powder vaccines will allow for more wide-spread vaccination programs and stockpiling of vaccines to better prepare for global pandemics.

It is well-known that the performance of the CS process is enhanced by increasing the process gas stagnation temperature, as this increases the gas velocity, and thus the particle velocity (kinetic energy). However, the influence of the initial substrate, coating, and particle impact temperatures on the CS process performance is still a topic that has barely been studied. This work focuses on establishing in a more systematic way how the initial substrate, coating, and particle impact temperatures affect the CS process performance by decoupling these three variables from the general spray parameters, namely the gas stagnation temperature. This decoupling is of crucial importance if one wants to be able to study the effect of each temperature and this approach has never been reported anywhere so far. In this work, two feedstock powder materials are used: pure aluminum and Inconel 718. The substrate material selected is Ti-6Al-4V. Therefore, the observations provided in this thesis are valid for the deposition of aluminum-on-Ti-6Al-4V and Inconel718-on-Ti-6Al-4V. To increase and control the initial substrate and coating temperatures while ensuring proper decoupling of other spray parameters, an induction heating system is used with the CS process. To control the initial particle temperature, independently from the gas stagnation temperature, powder preheater units are used. The powder is fed in the diverging section of the nozzle to avoid the uncontrollable heating usually observed by feeding the powder in the converging section. Single-particle impact testing and splat adhesion strength testing are carried out to evaluate the effect of the initial substrate temperature on individual particles. This is investigated using pure aluminum as the feedstock powder material. A finite element modeling is also carried out to complement the experimental results. The influence of the initial substrate temperature on the deposition process is quantified by measuring the deposition efficiency and coating porosity values. Micro-hardness testing and adhesion strength testing are used to characterized the as-sprayed coating mechanical properties. To study the influence of the coating temperature on the CS process performance, both powders, pure aluminum and Inconel 718, are used. The role of the coating temperature on the CS process is assessed by measuring the deposition efficiency and coating porosity values for the deposition of both powders. Micro-hardness, adhesion, and tensile strength measurements of the pure aluminum coatings is carried out. For the Inconel 718 coatings, only micro-hardness testing is conducted. To characterize the influence of the particle impact temperature on the CS process, Inconel 718 is used. The particle impact temperature is predicted using a computational fluid dynamics model. Deposition efficiency, coating porosity values, and micro-hardness testing are used to characterize the influence of the particle impact temperature on the CS process. The results in this thesis provide a path to optimize the CS process performance based on the influence of the initial substrate, coating, and particle impact temperatures. This work also demonstrates that other variables, such as particle impact velocity and feedstock powder material hardness, must also be considered to optimize the CS process performance through the use of different temperatures.

No description available.

Environmental monitoring is becoming increasingly important, primarily in urban areas due to the concentrated levels of human activities. The air sampling device presented is a novel method to sample air which harnesses the power of paper spray ionization paired with the intrinsic advantages of mass spectrometry such as high sensitivity, high selectivity, high throughput, and the ability to monitor multiple compounds at once.

No description available.

Lactobacillus acidophilus e Bifidobacterium lactis são microrganismos probióticos frequentemente utilizados em alimentos funcionais. No entanto, estes microrganismos devem resistir ao processamento, à estocagem do alimento, e sobreviver à passagem pelo trato-gastrointestinal, para chegarem ativos ao intestino e exercerem seus efeitos benéficos. Uma vez que os probióticos são sensíveis a uma série de fatores, tais como meio ácido, sais biliares e presença de oxigênio, a microencapsulação tem sido estudada com objetivo de protegê-los aos efeitos adversos do ambiente, além de promover a liberação controlada no local de ação do microrganismo, melhorando sua eficiência. Este trabalho teve como objetivo a produção e avaliação de micropartículas lipídicas contendo B. lactis ou L. acidophilus, produzidas por spray chilling, utilizando gorduras de baixo ponto de fusão, tais como gordura de palma e manteiga de cacau, como agente encapsulante. O diâmetro médio e a morfologia das partículas foram avaliados. Ensaios de sobrevivência foram conduzidos com objetivo de avaliar a resistência dos microrganismos ao processo encapsulação, resistência in vitro aos fluidos gástrico e intestinal simulados e estabilidade das células durante 90 dias de armazenamento a -18, 7 e 20 ou 37°C, dependendo da gordura utilizada. As micropartículasapresentaram-se em formato esféricoe com diâmetro médio que pode permitir o fácil escoamento no alimento, sem proporcionar impacto tecnológico negativo.A tecnologia de encapsulação por spray chilling, utilizando gordura de palma e manteiga de cacau, como agentes encapsulantes, proporcionou a obtenção de micropartículas eficientes na proteção dos probióticos frente ao processo de encapsulação e na manutenção da estabilidade das células quando estocados sob congelamento. Entretanto, aeficiência das micropartículas frente aos fluidos gastrointestinais e a estabilidade das células quando estocadas a 7 e 20 ou 37°C variaram de acordo com a gordura utilizada e com o microrganismo encapsulado. As micropartículas lipídicas obtidas são, portanto, uma matriz inovadora para a aplicação de probióticos, de baixo custo e com grande possibilidade de obtenção em escala industrial. O desafio futuro para o presente estudo é a seleção de um agente encapsulante que aumente a estabilidade das células, nas temperaturas ambiente e de refrigeração, a fim de aumentar as possibilidades de aplicação destas microcápsulas em produtos alimentícios. / L. acidophilus and Bifidobacterium lactis are probiotic microorganisms frequently used in food product. However they must remain viable during processing, entire shelf life of product and passing-through the gastrointestinal tract to provide beneficial effects on human health. Since theses microorganisms are sensitive to a series of factors, especially presence of oxygen and acid medium, microencapsulation has been studied as an alternative to increase probiotic cells viability and to provide the controlled release in the site of action, improving their efficiency. The aim of this study was to produce and evaluate lipid microparticles of L. acidophilus or B. lactis produced by spray chilling technology using low melting point fats, such as palm fat and cocoa butter, as the encapsulant agent. The mean diameter and morphology of the microparticles were evaluated. Survival assays were conducted to evaluate the resistance of the microorganisms to the spray chilling process, viability to the in vitro simulated gastric and intestinal fluids and viability during 90 days of storage at -18, 7 and 20/37°C, depending on the fat used. Microparticles presented a spherical shape and mean diameter that allows the flow of material in the food product without conferring technology influence. Spray chilling technology using fat palm or cocoa butter as the encapsulant agent was efficient in protecting the microorganism to the encapsulation process and 90 days of storage at -18°C. However the efficiency of the microparticles on the gastric and intestinal fluids and the cells stability during storage at 7 e 20 or 37°C varied according to the fat and microorganism used. The lipid microparticles seem to be a relatively innovative matrix for the application of probiotics with low costs and possibility of scale up. The future challenge in this study is to choose an encapsulant agent that improves cells resistance and viability at refrigerator and room temperatures to increase the possibility of application of these microcapsules in food products.

Coanda-assisted Spray Manipulation (CSM) is a means of modifying the direction of a jet. Previous isothermal static vectoring research is expanded to plasma spray. Two- dimensional Particle Image Velocimetry (PIV) was used to determine the vectoring results for small angles between 5-10°. Suitable parameters were determined for use on a plasma spray gun for small angle vectoring. Three-dimensional PIV was used to determine the elect of high speed rotation on a vectored jet. A 2-piece CSM collar was retrotted to a Praxair SG-100 plasma spray gun that replaced the standard faceplate. Two separate collars were tested: one designed for small vector angles and one for larger vector angles. The small-angle device could modify the trajectory of zirconia powder up to several degrees. Doing so could realign the plasma with the powder, resulting in increased powder temperature and velocity. The large-angle device could vector the plasma jet up to 45°; however the powder did not vector as much. Under large-angle vectoring, the powder velocity and temperature decreased steadily with vector angle. Both devices were tested using a supersonic conguration.

The aim of this study was to explore the properties of thermal field in spray cooling via experiments. The nozzle diameter (dj) used herein was 200 £gm and the heating surface measured 45 mm ¡Ñ 45 mm. The study was divided into two parts for experiments and analyses. In the first part, with DI water and FC-72 (dielectric liquid) as the working media, the changes in the liquid film thickness on the heater surface under different values of heating power were observed; heat input (Q) and value of gauge pressure (£GP) were taken as the main parameters for discussing the influence of these two parameters on the liquid film thickness in spray cooling. The second part, with DI water as the working medium, adopted the £gLIF system (fluorescent dye: Rhodamine B; concentration: 1.5¡Ñ10-4 M) to measure the effect of different working medium temperatures (23 ¢XC, 30 ¢XC, and 40 ¢XC) on the global temperature distribution, liquid film temperature changes on the heater surface and the thermal field condition of spray cooling, with an aim of exploring the internal physical phenomena of the droplets during cooling.

The aim of this study was to observe the properties of a spray field, with micro particle image velocimetry (£gPIV) and holographic interferometric particle imaging (IPI) employed for the imaging and analysis of the global spray field. The experiment adopted different nozzle diameters (dj = 200 £gm, and dj = 500 £gm) and different values of gauge pressure (£GP = 300 kPa, £GP = 500 kPa, and £GP = 700 kPa) as the main parameters, and DI (distilled) Water as the working medium. The study was divided into two parts. The first part used the £gPIV system to observe the two-dimensional global visualization of spray field distribution and spray angle from each nozzle under different values of gauge pressure (£GP). The flow velocity distribution and variations (axial velocity, and impact velocity) of the global spray frame were also measured. As the nozzle diameter would determine the distribution of spray droplets, the second part adopted the IPI system to measure and explore the atomized droplet sizes from each nozzle under different values of gauge pressure (£GP), whereby drop size histograms were created through statistical analysis.

L’objet de cette thèse est la synthèse et la caractérisation de nouveaux filtres UV inorganiques nanostructurés, efficaces dans le domaine des UVA. Dans ce contexte, nous avons choisi d’étudier le dioxyde de cérium (CeO2) et l’hématite (α-Fe2O3) en raison notamment de leurs propriétés optiques d’absorption des UV. Deux méthodes de synthèse ont été sélectionnées pour l’élaboration de ces oxydes, purs ou dopés, sous la forme de poudre nanométrique: la co-précipitation et le spray-pyrolyse. Les conditions optimales de synthèse ont été déterminées grâce à de la diffraction des rayons X et de l’analyse thermique. La structure cristalline ainsi que la granulométrie des échantillons obtenus ont été caractérisées par diffraction des rayons X et microscopies électroniques. La granulométrie et la morphologie des échantillons sont reliées aux méthodes de synthèse, aux conditions opératoires (atmosphère et température de calcination), à la nature et à la concentration des éléments dopants. Les propriétés optiques des échantillons suspendus dans de l’éthanol ont été étudiées par spectroscopie d’absorption UV-visible. Elles sont reliées à la granulométrie des échantillons ainsi qu’à des phénomènes localisés au sein de la maille cristallographique (changements de valence, présence de défauts). Les échantillons à base de CeO2 et α-Fe2O3 ont finalement été incorporés en émulsion solaire, à la place de ZnO, afin de tester leurs performances anti-solaires (SPF et FP-UVA) par mesure in vitro. Les résultats montrent que le ZnO peut être positivement remplacé dans les produits de protection solaire par l’oxyde de cérium ou de fer qu’ils soient purs ou dopés. / The subject of this thesis is the synthesis and the characterization of new UVA-efficient nanostructured inorganic UV filters. In this context, we chose to study cerium dioxide (CeO2) and hematite (α-Fe2O3), most importantly because of their optical absorption properties. Two methods were selected to synthesise cerium dioxide and hematite in nanostructured powder form: the co-precipitation method and the spray-pyrolysis method. Cerium dioxide was studied in both non-doped and doped forms. Optimal synthesis conditions were determined by X-ray diffraction and thermal analysis. The crystalline structure and granulometry of the obtained samples were characterised by X-ray diffraction and electronic microscopy techniques. Granulometry and morphology of the samples are linked to: the synthesis method, the experimental conditions (atmosphere and temperature of calcinations), and the nature and concentrations of the dopes. The optical properties of ethanol suspended samples were studied by UV-visible absorption spectroscopy. They are linked to the samples’granulometry as well as localised phenomena in the crystallographic lattice (valence changes, defects presence). Cerium dioxide- and hematite-based samples were finally incorporated in emulsion, instead of ZnO, in order to test their photoprotection performance (SPF and PF-UVA) by measuring in vitro. Results show that ZnO can be positively replaced by pure or doped cerium or iron oxide in sunscreen, when these are associated with the inorganic filter TiO2.