Neste trabalho foram desenvolvidos sistemas microfluídicos para aplicações na produção de micro e nanopartículas. Os dispositivos microfluídicos foram microfabricados em vidros do tipo borosilicato e em cerâmica verde LTCC (Low Temperature Co-fired Ceramic). Para os dispositivos em vidro foram utilizadas técnicas de fotolitografia, corrosão úmida e soldagem por cola UV. Com estas técnicas foram produzidos sistemas planares com diversas geometrias, sistemas com dispositivos em paralelo com duas e três camadas de vidros. Além disso, dois polímeros o Benzociclobuteno (BCB) e o Parylene-C foram apresentados como ferramenta para a modificação da superfície do vidro de hidrofílica para hidrofóbica. A cerâmica LTCC foi utilizada para a produção de um sistema microfluídico para focalização hidrodinâmica em 3 dimensões. Os dispositivos microfabricados foram utilizados para estudos sobre a produção de emulsões simples e duplas, observando a influência de parâmetros como taxa de fluxo, razão entre fluxos e diferentes tipos de emulsificantes no tamanho das gotas e no tipo de corte obtido em cada situação. Observou-se que o tamanho máximo das gotas obtidas fica restringido ao tamanho do canal microfabricado, cerca de 50m e o tamanho mínimo obtido foi de 15m. Além da produção de emulsões, foi estudada a produção de nanosuspensões pela técnica de nanoprecipitação anti-solvente. Para este estudo, além das geometrias planares, foram testadas as geometrias 3D e também sistemas para o aumento de escala de produção, onde o sistema integrado possuía 4 dispositivos para nanoprecipitação. Os resultados obtidos indicaram que os sistemas microfluídicos permitem a produção de nanopartículas amorfas, na faixa de 100 a 1000 nm, com baixa polidispersão, sendo ainda reprodutíveis em sistema de maior escala. O desenvolvimento deste trabalho mostrou que a microfluídica oferece ferramentas importantes na obtenção de micro e nanopartículas. / In this work microfluidic systems were developed for applications in micro and nanoparticles production. Microfluidic devices were microfabricated in borosilicate glasses substrates and LTCC ceramic (Low Temperature Co-fired Ceramic). For glass devices were used techniques such as photolithography, wet etching and UV glue for sealing glass wafers. With these techniques were manufactured planar systems with various geometries, systems with devices in parallel with two and three glass layers. In addition, two polymers, BCB and Parylene-C, were presented as a tool for glass surface modification, from hydrophilic to hydrophobic. The ceramic LTCC was used for the production of a microfluidic system for hydrodynamic focusing in three dimensions. The devices were used for studies on the single and double emulsions production, observing the influence of parameters such as flow rate, ratio between flows and different types of surfactants at the droplet size and droplet cut type obtained in each situation. It was observed that the maximum size of the droplets obtained is restricted by the channel size, the maximum was about 50m and the minimum size of 15m. Besides, the devices were used to produce nanoparticles using anti-solvent nanoprecipitation technique. For these studies, besides the planar geometries, 3D geometries were tested and also systems for increasing scale production, where 4 devices were integrated in one system for nanoprecipitation. The results indicated that the microfluidic systems allow the production of amorphous nanoparticles in the range of 100 to 1000 nm with low polydispersity, being also reproducible in a larger scale system. The development of this work has shown that microfluidics offers valuable tools in obtaining micro-and nanoparticles.

Neste trabalho foram desenvolvidos sistemas microfluídicos para aplicações na produção de micro e nanopartículas. Os dispositivos microfluídicos foram microfabricados em vidros do tipo borosilicato e em cerâmica verde LTCC (Low Temperature Co-fired Ceramic). Para os dispositivos em vidro foram utilizadas técnicas de fotolitografia, corrosão úmida e soldagem por cola UV. Com estas técnicas foram produzidos sistemas planares com diversas geometrias, sistemas com dispositivos em paralelo com duas e três camadas de vidros. Além disso, dois polímeros o Benzociclobuteno (BCB) e o Parylene-C foram apresentados como ferramenta para a modificação da superfície do vidro de hidrofílica para hidrofóbica. A cerâmica LTCC foi utilizada para a produção de um sistema microfluídico para focalização hidrodinâmica em 3 dimensões. Os dispositivos microfabricados foram utilizados para estudos sobre a produção de emulsões simples e duplas, observando a influência de parâmetros como taxa de fluxo, razão entre fluxos e diferentes tipos de emulsificantes no tamanho das gotas e no tipo de corte obtido em cada situação. Observou-se que o tamanho máximo das gotas obtidas fica restringido ao tamanho do canal microfabricado, cerca de 50m e o tamanho mínimo obtido foi de 15m. Além da produção de emulsões, foi estudada a produção de nanosuspensões pela técnica de nanoprecipitação anti-solvente. Para este estudo, além das geometrias planares, foram testadas as geometrias 3D e também sistemas para o aumento de escala de produção, onde o sistema integrado possuía 4 dispositivos para nanoprecipitação. Os resultados obtidos indicaram que os sistemas microfluídicos permitem a produção de nanopartículas amorfas, na faixa de 100 a 1000 nm, com baixa polidispersão, sendo ainda reprodutíveis em sistema de maior escala. O desenvolvimento deste trabalho mostrou que a microfluídica oferece ferramentas importantes na obtenção de micro e nanopartículas. / In this work microfluidic systems were developed for applications in micro and nanoparticles production. Microfluidic devices were microfabricated in borosilicate glasses substrates and LTCC ceramic (Low Temperature Co-fired Ceramic). For glass devices were used techniques such as photolithography, wet etching and UV glue for sealing glass wafers. With these techniques were manufactured planar systems with various geometries, systems with devices in parallel with two and three glass layers. In addition, two polymers, BCB and Parylene-C, were presented as a tool for glass surface modification, from hydrophilic to hydrophobic. The ceramic LTCC was used for the production of a microfluidic system for hydrodynamic focusing in three dimensions. The devices were used for studies on the single and double emulsions production, observing the influence of parameters such as flow rate, ratio between flows and different types of surfactants at the droplet size and droplet cut type obtained in each situation. It was observed that the maximum size of the droplets obtained is restricted by the channel size, the maximum was about 50m and the minimum size of 15m. Besides, the devices were used to produce nanoparticles using anti-solvent nanoprecipitation technique. For these studies, besides the planar geometries, 3D geometries were tested and also systems for increasing scale production, where 4 devices were integrated in one system for nanoprecipitation. The results indicated that the microfluidic systems allow the production of amorphous nanoparticles in the range of 100 to 1000 nm with low polydispersity, being also reproducible in a larger scale system. The development of this work has shown that microfluidics offers valuable tools in obtaining micro-and nanoparticles.

A comprehensive process intensification analysis was performed for the integration of the Pd-based membrane reactor technology into IGCC power plants by designing effective process control strategies as well as identifying and optimally characterizing inherently safe operational conditions to achieve the most favorable economic outcomes. Experimental results indicated that Pd-based composite membranes supported on porous stainless steel tubes, fabricated with H2 permeance values as high as ~50 m3/[m2.h.atm0.5] at 450°C were capable of extra purity H2 production (≥99.99%). Two illustrative process control and performance monitoring cases namely, process regulation and servo mechanism, were considered and quite satisfactory process control was attained by maintaining CO conversion at levels higher than 95% so that the retentate stream could become suitable for high pressure CO2 sequestration. From a process safety standpoint, process parameters and operating conditions were identified and optimized to achieve the target performance level of 98% CO conversion and 95% H2 recovery and at the same time to prevent conditions which could potentially induce hazards and thus compromise process system safety. Furthermore, the average total product cost of a water-gas shift membrane reactor module including manufacturing costs and general expenses was carefully estimated by taking into account the full cost structure and found to be 1464 $/ft2. Moreover, a comprehensive economic assessment was performed for composite Pd/Alloy membrane reactor technology options integrated into IGCC power plants in the presence of market and regulatory uncertainty (possible regulatory action on CO2 emissions) as well as technology risks with the aid of Monte-Carlo simulation techniques. Within such a context, it was demonstrated that an IGCC plant with embedded Pd-based membrane reactors and a stream of revenues coming from electricity and H2 selling (IGCC co-production mode), represented an economically attractive and advantageous option when comparatively assessed against its main competitors namely, an IGCC plant with shift reactors and double stage Selexol units as well as the more traditional supercritical pulverized coal power plant option with an Econamine unit installed for CO2 capture purposes.

La capture du dioxyde de carbone (CO2) en postcombustion est une stratégie importante pour la limitation de l’effet de serre. Le procédé de référence est l’absorption du CO2 dans des solutions aqueuses aminées, suivie par une étape de stripage du solvant. La technologie mature associée à ce procédé est la colonne à garnissage. Toutefois, afin de rendre le procédé plus attractif, il convient de l’intensifier en réduisant le volume des équipements et le coût énergétique associé. Les contacteurs membranaires à fibres creuses (CMFC) constituent une alternative aux colonnes à garnissage. Les CMFC permettent de développer d’importantes aires spécifiques conduisant potentiellement à une intensification des transferts gaz-liquide. Ainsi, l’utilisation des CMFC réduirait la taille des installations, mais aussi diminuerait la consommation énergétique par la diminution de la quantité de vapeur de stripage. Cependant, l’utilisation de CMFC dans les étapes d’absorption et de stripage dans des conditions industrielles a été peu étudiée. Afin de combler cette lacune, des modèles à différents niveaux de complexité : monodimensionnel, bidimensionnel, isotherme et adiabatique ont été développés, comparés et validés. Ceci afin d’identifier le niveau de complexité approprié. Les résultats de simulation ont mis en évidence le potentiel d’intensification des CMFC dans l’étape d’absorption et aussi de stripage, se traduisant par une réduction en volume de 4 à 10 fois par rapport aux colonnes à garnissage. Néanmoins, les CMFC peuvent difficilement réduire le coût énergétique du procédé étant donné que l’étape de stripage fonctionne dans des conditions très proches de la limite thermodynamique / Post-combustion CO2 capture (PCC) is an important strategy in mitigating greenhouse effect. The reference process in PCC is the CO2 absorption into amine aqueous solutions, followed by the regeneration (or stripping) of the solvent. The robustness of packed columns makes it the standard technology for both absorption and stripping steps. However, the treatment of large quantities of flue gases requires itself equipment of a large size. Hollow fibre membrane contactors (HFMC) are considered as one of the most promising strategies for intensified CO2 absorption process, due to their significantly higher interfacial area than that of packed columns, allowing to reduce the equipment size. In addition, this would reduce the energy penalty of the process by reducing the required amount of stripping steam. However, despite the potential advantages of HFMC, very few investigations have studied implementing this technology for PCC within an industrial framework. To fill this lack, the performances of both absorption and stripping steps using HFMC under industrial conditions were estimated by modelling and simulation. To identify the optimal modelling strategy, transfer models with different levels of complexity were developed ranging from one-dimensional isothermal single-component to two-dimensional adiabatic multi-component. Simulation results of both absorption and stripping steps revealed that, compared to traditional packed columns, contactor volume reduction factors comprised between 4 and 10 might be achieved using HFMC. However, since the stripping operating conditions are very close to thermodynamic equilibrium, HFMC can hardly reduce the energy consumption of the process

La présente étude a eu pour objectif la comparaison de la fabrication du biodiesel à partir de graines de caméline suivant les procédés conventionnels ou assistés/intensifiés par Détente Instantanée Contrôlée (DIC). La caméline est l'une des matières premières les plus adaptées à la fabrication de biodiesel puisqu’elle ne présente aucune concurrence aux cultures alimentaires et/ou à l’utilisation des terres agricoles. Son intérêt réside en sa teneur élevée en huile, sa courte saison de culture, ainsi que sa grande capacité à enrichir les sols pauvres, arides ou semi-arides. L'insertion de la texturation par DIC permet l'intensification à la fois de 1/ l'extraction de l’huile suivie de transestérification et 2/ du processus de transestérification in-situ en une seule étape. Dans les deux cas, les analyses statistiques ont conduit, à l'aide de la méthode de surface de réponse (RSM), à des modèles mathématiques empiriques adéquats capables de mieux développer les résultats expérimentaux, d'optimiser les paramètres de traitement et de mieux définir le changement d’échelle. Le procédé DIC se distingue par son aptitude à réaliser avec succès l’expansion structurelle des produits naturels sans affecter la qualité des huiles et des carburants produits. L'augmentation de la quantité d'huile extraite après texturation des graines par DIC a été de 38% et 22%, respectivement pour le pressage et l'extraction par solvant. En mode ISTE, la texturation DIC a permis de doubler le rendement en FAMEs. En outre, la technologie DIC est une technique très économique en raison de la grande capacité de traitement due au faible temps d’opération et d’une consommation réduite d'énergie. / The objective of this study was to compare the production of biodiesel from Camelina seeds using conventional methods or assisted/intensified by Instant Controlled Pressure-drop DIC. Camelina is one of the most suitable feedstocks for biodiesel production as it does not compete with food crops and/or agricultural land use. Its interest lies in its high oil content, short growing season, and great ability to enrich poor, arid or semi-arid soils. The insertion of texturing by DIC allows the intensification of both 1/ extraction of the oil followed by transesterification and 2/ a single step in-situ transesterification process. In both cases, using the response surface method (RSM), statistical analyzes have led to adequate empirical mathematical models capable of better developing experimental results, optimizing treatment parameters and better define the scaling-up. The DIC process stands out for its ability to successfully achieve the structural expansion of natural products without affecting the quality of sensitive compounds such as oils and fuels produced. The increase in the amount of oil extracted after DIC texturing of seeds was 38% and 22% for pressing and solvent extraction, respectively. In ISTE mode, DIC texturing approximately doubled FAMEs yields (98% increased yields). In addition, DIC technology is a very economical technique due to its high processing capacity, low operating time, and weak energy consumption.

Made available in DSpace on 2017-07-10T18:08:13Z (GMT). No. of bitstreams: 1 Vilmar Steffen.pdf: 1051925 bytes, checksum: 9d709f48cee722e3da025481c9af852b (MD5) Previous issue date: 2010-02-18 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Reactive distillation is the combination of chemical reaction and separation by distillation in only one equipment (these processes generally take place separately and in sequence in the industries of chemical processes). The integration of these two operations can increase the global performance of the production line. Thus, becomes necessary a previous study of the possibility to join these processes in a single equipment. The tool to start the study on a new process or the optimization of a process in operation is the modeling and simulation. The mathematical models for reactive distillation columns are constituted of a system of non linear equations. Several algorithms for simulation of distillation columns in steady state with different degrees of precision and consequently of difficulties were developed in the last decades. However, these algorithms don't supply a procedure to obtain the initial guesses, that are fundamental for the convergence of the method used to solve the system of non linear equations. In this work was developed an algorithm for the solution of mathematical model that describes the reactive distillation process in columns that operates in steady state. In the developed algorithm was defined a procedure to obtain reasonable initial guesses that facilitates the convergence of the method. The great majority of methods for simulation of distillation column in stead-state solve all the equations simultaneously by a system of non linear equations solution s method. In this work was developed an algorithm step-by-step, to facilitate it s understanding, where the system of non linear equations solution s method is necessary just for the group of equations that models the chemical reactions, so that, two system of non linear equations solution s methods were used, the method of Broyden (a variation of the Newton-Raphson s method) and the homotopy continuation method (or homotopy). The mathematical model was obtained from mass balances, energy balances, sum equations, phase equilibrium and chemical equilibrium or chemical kinetics. The modeling of phase equilibrium is rigorous by means of the calculation of activity and fugacity coefficients, the modeling of the thermal effects is also rigorous by means of the calculation of the residual and excess enthalpies. The developed algorithm was evaluated from examples of the literature and in all cases the obtained results were similar to those found in the literature. / Destilação reativa é a combinação de reação química e separação por destilação em um único equipamento (geralmente estes processos acontecem separadamente e em seqüência nas indústrias de processos químicos). A integração destas duas operações pode aumentar o desempenho global da linha de produção. Desta forma, torna-se necessário um estudo prévio da possibilidade de se reunir estes processos em um só equipamento. A ferramenta para se iniciar o estudo sobre um novo processo ou a otimização de um processo em operação é a modelagem e simulação. Os modelos matemáticos para a coluna de destilação reativa são constituídos de um sistema de equações não lineares. Vários algoritmos para simulação de colunas de destilação em regime permanente com diferentes graus de precisão e consequentemente de dificuldades foram desenvolvidos nas últimas décadas. Entretanto, estes algoritmos não fornecem um procedimento para a obtenção de estimativas iniciais, que são fundamentais para convergência do método utilizado para resolver o sistema de equações não lineares. Neste trabalho foi desenvolvido um algoritmo para resolução do modelo matemático que descreve o processo de destilação reativa em colunas que operam em regime permanente. No algoritmo desenvolvido definiu-se um procedimento de obtenção de estimativas iniciais razoáveis que facilitem a convergência do método. A grande maioria dos métodos para simulação de coluna de destilação em estado estacionário resolve todas as equações simultaneamente com um método de solução de sistema de equações não lineares. Neste trabalho foi desenvolvido um algoritmo passo-a-passo, para facilitar a compreensão do mesmo, onde o método de solução de sistemas de equações não lineares é necessário apenas para o conjunto de equações que modelam as reações químicas, para tal, foram utilizados dois métodos de solução de sistemas de equações não lineares, o método de Broyden (uma variação do método de Newton-Raphson) e o método da continuação homotópica (ou homotopia). O modelo matemático utilizado foi obtido a partir de balanços de massa, balanços de energia, equações de somatória, equilíbrio de fases e equilíbrio químico ou cinética química. A modelagem do equilíbrio de fases é rigorosa por meio do cálculo de coeficientes de atividade e fugacidade, a modelagem dos efeitos térmicos também é rigorosa por meio do cálculo das entalpias residual e de excesso. O algoritmo desenvolvido foi avaliado a partir de exemplos da literatura e em todos os casos os resultados obtidos foram semelhantes àqueles encontrados na literatura.

No description available.

<p>  </p> <p>Crystallization is a purity and particle control unit operation commonly used in industries such as pharmaceuticals, agrochemicals, and energetics. Often, the active ingredient’s crystal mean size, polymorphic form, morphology, and distribution can impact the critical quality attributes of the final product. The active ingredient typically goes through a series of process development iterations to optimize and scale-up production to reach production scale. Guided by the FDA, the paradigm shift towards continuous processing and crystallization has shown benefits in introducing cheaper and greener technologies and relieving drawbacks of batch processing. To achieve successful batch scale-up or robust continuous crystallization design, process intensification of unit operations, crystallization techniques, and utilizing data driven approaches are effective in designing optimal process parameters and achieving target quality attributes. </p> <p>In this thesis, a collection or toolbox of various process intensification techniques was developed to aid in control, optimization, and digitalization of crystallization processes. The first technique involves developing a novel control algorithm to control agrochemical crystals of high aspect ratio to improve the efficiency of downstream processes (filtration, washing, and drying). The second technique involves the further improvement of the first technique through digitalization of the crystallization process to perform simulated optimization and obtain a more nominal operating profile while reducing material consumption and experimentation time. The third method involves developing a calibration procedure and framework for in-line video microscopy. After a quick calibration, the in-line video microscopy can provide accurate real-time measurements to allow for future control capabilities and improve data scarcity in crystallization processes. The last technique addresses the need for polymorphic control and process longevity for continuous tubular crystallizers. Through a sequential stirred tank and tubular crystallizer experimental setup, the control of polymorphism, particle mean size, and size distribution were characterized. Each part of this thesis highlights the importance and benefits of process intensification by creating a wholistic process intensification framework coupled with novel equipment, array of PAT tools, feedback control, and model-based digital design.</p>

<p dir="ltr">The purification of most active pharmaceutical ingredients (APIs) is primarily achieved through crystallization, conducted in batch, semi-batch, or continuous modes. Recently, continuous crystallization has gained interest in the pharmaceutical industry for its potential to reduce manufacturing costs and maintenance. Crystal characteristics such as size, purity, and polymorphism significantly affect downstream processes like filtration and tableting, as well as physicochemical properties like bioavailability, flowability, and compressibility. Developing an optimal operation that meets the critical quality attributes (CQAs) of these crystal properties is essential.</p><p dir="ltr">This dissertation begins by focusing on designing an innovative integrated crystallization system to enhance control over crystalline material properties. The system expands the attainable region of crystal size distribution (CSD) by incorporating multiple Mixed-Suspension Mixed-Product Removal (MSMPR) units and integrating wet milling, classification, and a recycle loop, enhancing robustness and performance. Extensive simulations and experimental data validate the framework, demonstrating significant improvements in efficiency and quality. The framework is further generalized to optimize crystallizer networks for controlling critical quality attributes such as mean size, yield, and CSD by evaluating various network configurations to identify optimal operating parameters.</p><p dir="ltr">The final part of this work concentrates on using the framework to improve continuous production of a commercial API, Atorvastatin calcium (ASC), aiming for higher yield and lower costs. This approach establishes an attainable region to increase crystal sizes and productivity. Due to ASC’s nucleation-dominated nature, the multi-stage system could not grow the crystals sufficiently to bypass granulation, the bottleneck process in ASC manufacturing. Therefore, spherical agglomeration was proposed as an intensification process within an integrated two-stage crystallization spherical agglomeration system to control the size and morphology of ASC crystals and improve downstream processing and tableting. This method proved highly successful, leading to the development of an end-to-end continuous manufacturing process integrating reaction, crystallization, spherical agglomeration, filtration, and drying. This modular system effectively addressed challenges in integrating various unit operations into a coherent continuous process with high production rates.</p>

Actuellement produit à partir du pétrole, une voie de synthèse de l'acide acrylique (AA) à partir du glycérol est envisagée. Cependant, cet AA bio-sourcé contient davantage d'acide propionique (AP) que l'AA issu du propylène. Les techniques classiques de purification ne permettent pas de séparer les deux acides. Le diagramme de phases liquide-solide du binaire AA + AP est déterminé. Il présente un point eutectique à 25,65 % (mol) d'AA, un point péritectique à 50,00 % (mol) d'AA et donc, un large domaine dans lequel l'AA cristallise thermodynamiquement de façon pure. Les essais de purification en mode statique sur paroi froide affichent des résultats prometteurs, une efficacité de séparation correcte pour un rendement de 60 %. Afin d'améliorer les transferts de matière et de chaleur, des dispositifs en mode dynamique sont mis au point dont un cristallisoir en film tombant. Ce dispositif permet de multiplier par 2,8 la productivité, tout en conservant une bonne efficacité de séparation. Afin de diminuer la surfusion et de maintenir un bon transfert thermique malgré une couche cristalline relativement isolante, des surfaces de cristallisation micro- et milli-structurées sont envisagées. La productivité est encore améliorée et la modélisation du transfert thermique confirme ces résultats expérimentaux. Afin de se rapprocher des conditions industrielles, un brut synthétique de bio-AA est purifié. La cristallisation en milieu fondu permet de séparer toutes les impuretés testées. Enfin, un modèle de cascade de cristallisoirs fermés, avec recyclage des différentes phases, est proposé afin de dimensionner le procédé global. Les essais en conditions presque réelles et l'intensification du procédé de cristallisation permettent d'envisager sereinement la mise en oeuvre du procédé industriel / With a global market exceeding four million tons per year, acrylic acid (AA) is a major intermediate chemical. The current AA synthesis is based on propylene, which is produced from oil. Thus, a novel production route is envisioned, based on glycerol, a green byproduct of oleochemistry and biodiesel production. However, current crude biobased AA contains a higher proportion of PA than AA from petrochemical origin. Classical purification techniques of AA cannot efficiently separate these two chemicals. In a first part, liquid-solid phase diagram of the binary system AA + PA is determined. This liquid-solid equilibrium exhibits an peritectic behavior at 50.0% (mol) of AA, a eutectic point at 25.65% (mol) of AA and thus, this diagram is favorable to the purification of AA. First purification tests by static solid layer melt crystallization show promising results: a correct separation efficiency for a yield varying between 60 et 70 %. To improve heat and mass transfer, dynamic crystallization set-up are developed, including a falling film crystallizer. This set-up multiplies by 2.8 the productivity of purification, while keeping a good separation efficiency. To reduce supercooling and to keep a good heat transfer despite the crystalline layer which is a thermal insulator, micro-and milli-structured crystallization surface are considered. Productivity is further improved and heat transfer modeling confirms the experimental results. To be nearer to industrial conditions, synthetic crude bio-AA is purified. Melt crystallization can separate all the impurities which are present in the medium. To scale-up the overall process a cascade model of batch crystallizers with recycling of the differents phases, is proposed. The intensification of the melt crystallization process permits to consider the implementation of the industrial process