L’énantiomère R (énantiomère cible) d’un mélange racémique d’une molécule organique est isolé par cristallisation du sel diastéréoisomère qu’il forme préférentiellement en s’associant à l’acide énantiomériquement pur R-acétyl(L)valine. Cependant l’énantiomère S (contre-énantiomère) peut aussi cristalliser sous forme d’un sel de R-acétyl(L)valine. Les solubilités des deux sels sont déterminées par des cristallisations par refroidissement en réacteur fermé. La modélisation de ces données expérimentales permet de maximiser la quantité d’énantiomère R cristallisé en sel pur en réacteur fermé à une température choisie. Cette température est ensuite augmentée : la durée de filtration des cristaux, systématiquement obtenus sous forme d’aiguilles, est avantageusement réduite. Une réduction est encore obtenue en appliquant un profil de refroidissement favorisant la croissance des cristaux : au final, l’amélioration de la filtrabilité des cristaux est corrélée aux augmentations conjointes du facteur d’élongation et de la longueur des cristaux. La cristallisation est ensuite transposée à un mode de fonctionnement continu en injectant les réactifs séparément dans un réacteur ouvert. Afin d’atteindre des performances égales à celles du réacteur fermé, le temps de passage et la concentration de la solution de R-acétyl(L)valine sont ajustés : il en résulte une productivité accrue de la cristallisation. La filtrabilité des cristaux obtenus en réacteur continu reste cependant médiocre. Bien que toujours inférieur à celui atteint en réacteur fermé optimal, le facteur d’élongation des cristaux est tout de même augmenté en optant pour une configuration de cascade de deux réacteurs continus / The R enantiomer (target enantiomer) of the racemic mixture of an organic molecule is isolated by a preferential crystallization of the salt it forms by association with the enantiomerically pur acid R-acetyl(L)valine. The S enantiomer (counter enantiomer) may somehow also crystallize under the form a R-acetyl(L)valinate salt. Solubilities of the two salts are measured by cooling crystallizations in a batch reactor, carried out for various stoechiometric conditions. The interpretation and the modelisation of the experimental data gathered lead to the maximisation of the quantity of R enantiomer crystallized as a pur salt in a batch reactor by cooling crystallization to a given temperature. This temperature is then increased : the filtration duration of the crystals, always exhibiting the shape of needles, is thus advantageously decreased. A further decrease is made possible by applying a temperature cooling profile that promotes the growth of crystals. Finally, the enhancement of the filterability of crystals is correlated to an increase of the elongation factor of crystals. The crystallization is then transposed to a continuous operating mode : reactants are injected separately in a continuous stirred tank reactor. With a view to match the results of the optimized batch reactor, the residence time and the R-acetyl(L)valine concentration are adjusted : a better productivity is then obtained, though filterability remains lower. The elongation factor is slightly increased by implementing two continous stirred tank in serie. The complete range of possible enhancements of crystals morphology by such cascades could be further studied for such needle-like crystals

<p>There are many types of bioreactors used for producing bacteria populations in commercial, medical and research applications. </p><p>This report presents a systematic discussion of some of the most important models corresponding to the well known reproduction kinetics such as the Michaelis-Menten kinetics, competitive substrate inhibition and competitive product inhibition. We propose a modification of a known model, analyze it in the same manner as known models and discuss the most popular types of bioreactors and ways of controlling them. </p><p>This work summarises much of the known results and may serve as an aid in attempts to design new models.</p>

There are many types of bioreactors used for producing bacteria populations in commercial, medical and research applications. This report presents a systematic discussion of some of the most important models corresponding to the well known reproduction kinetics such as the Michaelis-Menten kinetics, competitive substrate inhibition and competitive product inhibition. We propose a modification of a known model, analyze it in the same manner as known models and discuss the most popular types of bioreactors and ways of controlling them. This work summarises much of the known results and may serve as an aid in attempts to design new models.

Two computer programs were developed and used to determine the optimum operating parameters of a fedbatch and a continuous two-stage process for fermentation of recombinant bacteria. The study was conducted in three phases: (a) developing two computer programs for simulation and optimization of the above processes, (b) conducting batch culture fermentations to verify the performance of the biokinetic model, and (c) conducting fedbatch and two-stage continuous fermentation experiments to closely examine the simulation and optimization results. The Miao and Kompala (1992) biokinetic model was used for simulation of the bacterial growth and cloned gene expression. The Pattern-Search method, developed by Hooke and Jeeves (1962), was incorporated in the programs to determine the optimum values of the parameters. Extensive studies of the optimization results showed 30-40% higher productivities for the two stage continuous process over the fedbatch process when using the same media in both processes. In addition, increasing the number of stages in the continuous two-stage process resulted in very limited improvement in the productivity of the process (10-12%). The information from the process optimization was then used to design batch, fedbatch nd two stage continuous experiments. Recombinant <i>E. coli </i>(strain BL21DE3) with an inducible gene (sensitive to IPTG, isopropyl-â-D-thiogalactopyranoside) was used throughout the experiments. The experimental results from the fedbatch and two stage continuous processes clearly showed good agreement with the simulation and optimization results $(\cong$15% deviation). The experiments also revealed that the maintenance of plasmid harboring cells over the long-term operation could be an important barrier in achieving the predicted high productivity in the two stage continuous process. Finally, in addition to computer programs for optimization of genetically modified microorganisms, a new computer program with a generic algorithm for optimization of multiple CFSTR fermentation with any kind of biokinetic model was developed. The program was used to optimize multiple CFSTRs with the cybernetic biokinetic model for the first time. Besides finding the optimum residence times for multiple CFSTRs operation, the effect of inaccuracies in different cybernetic model parameters on the overall productivity of the process was investigated. The simulation results illustrated that, a single CFSTR was more sensitive in its operation to inaccuracies in the biokinetic constants as compared to optimized CFSTRs in series (2-8 times more sensitive).

Le micromélange, ou mélange à l'échelle moléculaire, a une influence déterminante sur la qualité des produits, la sélectivité, et le rendement de réactions d'importance industrielle comme les réactions de polymérisation. A l'heure actuelle, les systèmes chimiques existants sont bien adaptés à l'étude du micromélange de produits faiblement visqueux, mais il n'existe pas de méthode simple et opérationnelle pour les fluides plus visqueux. Inscrite dans le cadre du projet ANR PROCIP, l'étude a consisté à mettre en place une nouvelle méthode de quantification de l'efficacité du micromélange en milieu visqueux dans des réacteurs agités. La méthode utilisée s'inspire d'un système chimique basé sur deux réactions concurrentes, le système de réaction test iodure-iodate, dont la sélectivité d'un des produits est une mesure de l'efficacité du micromélange. L'approche propose un nouveau protocole basé sur le choix d'un tampon phosphate et l'utilisation de l'HydroxyEthylCellulose (HEC, 720 000 g/mol) comme agent viscosifiant inerte, qui possède un fort pouvoir viscosifiant permettant d'augmenter significativement la viscosité sans en ajouter plus de 1 % en masse dans le milieu. Des essais de caractérisation du micromélange en réacteur agité ont mis en évidence le ralentissement du micromélange au fur et à mesure que la viscosité augmente pour des pourcentages en HEC inférieurs à 0,5 %. Par contre, au-delà de 0,5 %, une « amélioration » du micromélange a été observée dans une large gamme de conditions expérimentales (différentes concentrations de réactifs, positions de l'injection, vitesses d'agitation et mobiles d'agitation). Plusieurs causes potentielles ont été formulées en vue d'expliquer ce phénomène et les cinétiques des réactions mises en jeu ont également été étudiées en présence de l'agent viscosifiant HEC et s'avèrent être inchangées. Enfin, une étude des interactions possibles entre les espèces iodées et l'HEC a été réalisée pour étudier l'existence d'une réaction parasite qui pourrait expliquer les résultats obtenus / Micromixing, or mixing at the molecular scale, has a decisive influence on product quality, selectivity and yield of industrially important reactions such as polymerization reactions. Currently, the existing chemical systems are well suited to the study of micromixing of low viscosity products, but no reliable characterization method exists for highly viscous media. As a part of the ANR project PROCIP, the study consisted in developing a new method to quantify the efficiency of micromixing in viscous media in stirred reactors. The method used is inspired by a chemical system based on two competitive reactions, the iodide-iodate test reaction system whose selectivity of a product is a measure of the micromixing efficiency. The approach proposes a new protocol based on a phosphate buffer and the use of HydroxyEthylCellulose (HEC, 720,000 g / mol) as an inert viscosifying agent, enabling to significantly increase the viscosity without adding more than 1 % by mass in the medium. Characterization of micromixing in a stirred reactor showed the slowing down of micromixing as viscosity increases for percentages of HEC below 0.5 %. By contrast, above 0.5 %, an "improvement" of micromixing has been observed in a wide range of experimental conditions (different concentrations of reactants, injection positions, stirring speeds and impellers). Several possible causes have been made to explain this phenomenon unexpected and the kinetics of the reactions involved were also studied in the presence of the viscosifying agent HEC and appeared to be unchanged. Finally, a study of possible interactions between iodine species and HEC was performed to study the existence of a secondary reaction which could explain the results

Un grand nombre d’industries (chimiques, pharmaceutiques et agroalimentaires) utilisent, produisent ou transforment des fluides complexes. Ce sont des fluides à viscosité élevée, souvent de comportement non-Newtonien. Leur préparation nécessite souvent une étape de chauffe suivie d’une étape de refroidissement. La chauffe est indispensable afin de faciliter la fabrication (réaction chimique et/ou transformation physico-chimique). Le refroidissement, ou encore l’étape de finition, consiste à amener les fluides jusqu’à une température proche de la température ambiante pour aborder l'étape de conditionnement. Le refroidissement est le plus souvent réalisé « in situ » dans la même cuve agitée, équipée d’une double enveloppe (utilisée pour la fabrication), mais des technologies en continu peuvent également être envisagées. Ces travaux de thèse portent sur la mise en place d’une méthodologie de pilotage de la vitesse d’agitation lors du refroidissement de fluides complexes dans des cuves agitées, ainsi que sur la comparaison des performances de la cuve agitée avec celles du mélangeur statique. Deux fluides de travail sont testés : Newtonien et viscoplastique, en régime d’écoulement laminaire et transitoire. Nous déterminons les limites de l’influence de l’agitation sur le transfert thermique, la durée de l’opération et la quantité d’énergie consommée. En premier lieu, le refroidissement est étudié à l’échelle laboratoire (réacteur de 0,6L). Il a été constaté que le changement de la vitesse d’agitation au cours du refroidissement affecte le profil de température. Cela a un impact avantageux sur le coût énergétique et/ ou la durée de refroidissement. Les tendances observées à l’échelle laboratoire sont transposées et validées à l’échelle pilote (réacteur de 60L). Puis deux types de mélangeurs statiques sont étudiés comme technologie en continu. Nous établissons des modèles de perte de charge que nous utilisons dans la détermination de l’énergie dépensée pour le refroidissement. Ensuite nous réalisons une comparaison de leurs performances en fonction des facteurs d’efficacité de transfert thermique et de consommation énergétique. Enfin, une brève analyse comparée est exposée, présentant les divers critères de choix entre la cuve agitée et la technologie en continu. / Highly viscous Newtonian and non-Newtonian fluids are frequently encountered in the process industries (like pharmaceutical, food and cosmetics). The preparing of such products involves heating and cooling steps. The heating stage is essential in order to facilitate the production (chemical reaction and/or physico-chemical transformation). The cooling step, named also final stage, leads the fluids to ambient temperature and prepares them for the conditioning. The cooling is mostly realized "in situ" in the same double jacketed stirred vessel, (used for the manufacturing), but continuous technologies may also be employed. This study aims to investigate the cooling of highly viscous fluids, and intends to define the best conditions for controlling the impeller speed (constant or variable) in a stirred vessel, as well as to compare the performances of the stirred vessel with those of the static mixer. Two fluids are tested: a Newtonian and a Non-Newtonian yield-stress fluid, in laminar and transitional conditions. The limits of the influence of the impeller speed on the heat transfer, the duration and the energy consumption are determined. In a first approach, the cooling is studied at small scale (0,6L vessel). The variation of the impeller speed during the cooling, affects the profile of temperature. This type of procedure has an advantageous impact on the energy cost and / or the duration of the cooling. The observed tendencies at a small scale are transposed and validated at a pilot scale (60L vessel). Two types of static mixers are studied as continuous technology. Models of pressure drop are established, which are used further in the determination of the energy consumption for the cooling. The performances of these two static mixers are compared, according to the factors of heat transfer efficiency and energy consumption. Finally, a brief comparative analysis is exposed, presenting diverse criteria of choice between the stirred tank and the continuous technology.

Submitted by Neusa Fagundes (neusa.fagundes@unioeste.br) on 2017-09-05T19:08:26Z No. of bitstreams: 1 Thiago_Edwiges2017.pdf: 2041114 bytes, checksum: f435c702dd49431aa0534c4ce49e2533 (MD5) / Made available in DSpace on 2017-09-05T19:08:26Z (GMT). No. of bitstreams: 1 Thiago_Edwiges2017.pdf: 2041114 bytes, checksum: f435c702dd49431aa0534c4ce49e2533 (MD5) Previous issue date: 2017-08-18 / The economical development and urbanization process have contributed to the increase in solid waste generation and problems related to final disposal. Thus, the National Solid Waste Policy reinforces treatment in order to improve efficiency in the management of solid waste as one of its priorities and stimulates to recover and use energy. Anaerobic digestion has been suggested as a promising approach to the treatment of organic fraction of solid waste, mainly because it represents an opportunity to reduce environmental pollution and minimizes impacts concerning the energy crisis. So, this trial aimed at evaluating FVW biogas potential, collected in a wholesale market (Unit from Foz do Iguaçu/PR) through batch and semicontinuous tests. Fruits and vegetables trading from that unit generates approximately 70,500 t year-1, with 2,800 kg d-1 solid waste, composed of almost 85% organic matter. The influence of chemical composition of twelve FVW different samples with different compositions on biochemical methane potential (BMP) was analyzed. The BMP ranged from 288 LN CH4 kg VS-1 to 516 LN CH4 kg VS-1, with significant statistical differences among means. This was explained by in the waste chemical composition over time. BMP variation was most strongly correlated for lipid content and high calorific values (HCV). Linear regression analyses were carried out to develop statistical models to predict as fast as possible methane potential of this kind of waste. The models were analyzed according to chemical compounds and HCV based on simple and multiple regression. The model with the best statistical metrics included lipid, protein, cellulose, lignin, and HCV, with a 92.5% R² and lignin content negatively correlated to BMP. Since HCV and lipids were strongly correlated, and because HCV can be determined more rapidly than chemical composition, HCV may be useful for predicting BMP. In addition to batch tests, the performance of anaerobic digestion was also investigated in a semicontinuous mode using a FVW mixture as a single substrate. The performance of a continuous stirred tank reactor (CSTR) was monitored along with the gradual increase of organic loading rates (OLR) from 0.5 gVS L–1 d–1 to 5.0gVSL–1d–1. BMP of FVW used as a feedstock to CSTR was 370 LN CH4 kg VS-1 with 81% biodegradability. During the whole trial pH was stable and there was an adequate level of buffering capacity in the system. Volumetric biogas production (LN biogas L–1 d–1) increased linearly (R² = 94.4%) according to OLR increase. On the other hand, the specific methane production (LN CH4 kg VS-1) has registered the best performance at an OLR of 3.0 g VS L–1 d–1 and 30 days of hydraulic retention time, with 285 LN CH4 kg VS-1 added, reaching 74% of BMP measured by batch tests. A clear accumulation of volatile fatty acids (VFA) was monitored with a decreased specific methane yield was detected with an OLR above 3.0 g VS L–1 d–1. / O crescimento econômico e o processo de urbanização vêm contribuindo para o aumento da geração de resíduos sólidos e problemas relacionados à disposição final. A Política Nacional de Resíduos Sólidos reforça o tratamento com o intuito de melhorar a eficiência quanto ao gerenciamento dos resíduos sólidos no país, como uma de suas prioridades e enfatiza o incentivo à recuperação e ao aproveitamento energético. A biodigestão anaeróbia tem sido apontada como uma abordagem promissora ao tratamento da fração orgânica dos resíduos sólidos, sobretudo por representar oportunidade de reduzir a poluição ambiental e minimizar os impactos da crise energética. Assim, o objetivo deste trabalho foi avaliar o potencial de produção de biogás de resíduos de frutas e hortaliças (RFH) coletados na Central de Abastecimento (CEASA – Unidade de Foz do Iguaçu/PR) a partir de testes em batelada e em regime semicontínuo. A comercialização de frutas e hortaliças da unidade é de aproximadamente 70.500 t ano-1, com geração de resíduos sólidos de 2.800 kg d-1, compostos por aproximadamente 85% de matéria orgânica. A influência da composição química de doze amostras de RFH com diferentes composições sobre o potencial bioquímico de metano (PBM) foi analisada. O PBM dos resíduos variou entre 288 LN CH4 kg SV-1 e 516 LN CH4 kg SV-1, com diferenças estatísticas significativas entre as médias, o que pôde ser explicado pela variação na composição química dos resíduos ao longo do tempo. A variação do PBM foi mais fortemente correlacionada à variação do teor de lipídeos e do poder calorífico superior (PCS). Foram realizadas análises de regressão linear visando desenvolver modelos estatísticos para estimar, de forma mais rápida, o potencial metanogênico deste tipo de resíduo. Os modelos foram analisados considerando os componentes químicos e o PCS a partir de regressão linear simples e múltipla. O modelo com as melhores métricas estatísticas foi obtido considerando lipídio, proteína, celulose, lignina e PCS, com R² de 92,5% e com teor de lignina negativamente correlacionado ao PBM. Como o PCS e os lipídeos apresentaram forte correlação, e como o PCS pode ser determinado, em geral, de forma mais rápida que a composição química, o PCS pode ser considerado um parâmetro útil para a estimava do PBM. Além dos testes em batelada, investigou-se também o desempenho da biodigestão anaeróbia em regime semicontínuo utilizando-se uma mistura de RFH como único substrato. O desempenho de reator de mistura completa (do inglês CSTR) foi monitorado juntamente com o aumento gradativo da carga orgânica volumétrica (COV) de 0,5 g SV L-1 d-1 até 5,0g SV L-1 d-1. O PBM dos RFH utilizado para alimentar o reator foi 370 LN CH4 kg SV-1 com biodegradabilidade de 81%. Durante todo o ensaio o pH se manteve estável e o sistema apresentou boa capacidade tampão. A produção volumétrica de biogás (LN biogás L-1 d-1) aumentou de forma linear (R² = 94,4%) de acordo com aumento da COV. Já a produção específica de metano (LN CH4 kg SV-1) indicou o melhor desempenho com COV de 3,0 g SV L-1 d-1 e 30 dias de tempo de retenção hidráulica, com 285 LN CH4 kg SV-1 adicionados, e atingiu 74% de PBM, medido a partir dos testes em batelada. Observou-se um acúmulo evidente de ácidos graxos voláteis (AGV), com consequente redução da produção de metano a partir da COV acima de 3,0 g SV L-1 d-1.

In der vorliegenden Arbeit wird die Konzeptionierung und die Realisierung eines teilkontinuierlichen Thermolyseverfahrens zur rohstofflichen Verwertung von Polyethylen- und Polypropylenabfällen beschrieben. Die Ausführung in der zweistufigen Rührkesselkaskade gewährleistete dabei die Trennung der Prozessschritte Schmelzen sowie Cracken der Einsatzmaterialien, woraus ein Thermolyseöl hervorging, welches weitestgehend frei von den Verunreinigungen aus den Abfällen war. Das Thermolyseöl wies eine Zusammensetzung aus Benzin- und Dieselkomponenten auf und erfüllte einige entscheidende Kraftstoffkriterien. Zur Senkung der qualitätsmindernden Olefingehalte wurden in einem weiteren Teil dieser Arbeit Untersuchungen zur heterogen-katalysierten Hydrierung der Siedeschnitte im Schüttgutreaktor und im Rührautoklav durchgeführt. Dabei konnten die Olefingehalte durch den Einsatz eines Palladium-Platin-Trägerkatalysators sowie durch einen Nickel-Gerüstkatalysator maßgeblich gesenkt werden. Als unerwünschtes Nebenprodukt des Thermolyseprozesses resultierte ein geringer Anteil Koks, welcher in der Schmelze akkumulierte und sich teilweise an der Reaktorwand ablagerte. Die entstandenen Mengen wiesen eine Abhängigkeit von der Prozesstemperatur und -dauer auf und mussten aus dem Prozess geschleust werden. Als weitere Nebenprodukte traten ein leichtflüchtiges Spaltgas sowie ein Sumpfrückstand auf. Darüber hinaus wurde gezeigt, dass die aufzuwendende Energie für den Thermolyseprozess durch die Energiegehalte der Nebenprodukte gedeckt werden kann. Neben dem Einsatz als Kraftstoff empfahl sich das Thermolyseöl aufgrund seiner physikalischen und chemischen Eigenschaften gerade im Hinblick auf einen nachhaltigen Umgang mit Ressourcen als beachtenswerter Ersatz für fossiles Rohöl.

This work investigates the fluid flow in a cylindrical millilitre vial stirred by a magnetic stirred bar using Computational Fluid Dynamic (CFD). Stirred millilitre vials are used to study nucleation phenomena and crystallization as an outline of literature study of nucleation and crystallization phenomena and the role of stirring in this process. The baffle free vial was meshed with around 500,000 cells. To simulate the stirring a rotary frame and moving walls were used. Stirring speeds were between 100 and 1000 rpm where considered, correspondently to a stirrer Reynolds number between 260 and 2600. For stirring speeds bellow 500 rpm, simulations by both the both laminar flow model and the k-ε model where run, while above 500 rpm only k-ε was used. Results of the two models were very similar indicative the adequacy of k-ε to simulate the flow even at low Reynolds. The flow shows expected circulation pattern with upwards pumping close to side walls and downwards pumping in the centre of cylindrical vial. At 1000 rpm circulation patterns expands up to the top of the vial while at 300 rpm and lower the upper half of the vial is poorly mixed. The average turbulent energy of the flow is very low comparing with the squared stirrer tip speed and the power number decrees with Reynolds number, indicating that the flow is not fully turbulent.

The loss of efficiency and performance of bioprocesses on scale-up is well known, but not fully understood. This work addresses this problem, by studying the effect of some fermentation gradients (pH, glucose and oxygen) at a larger scale in a bench-scale two compartment reactor (PFR + STR) using the cadaverine-producing recombinant bacterium, Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT. The initial scale down strategy increased the magnitude of these gradients by only increasing the mean cell residence time in the plug flow reactor (τ_PFR). The cell growth and product related rate constants were compared as the τ_PFR was increased; differences were significant in some cases, but only up to 2 min residence time. For example, losses in cadaverine productivity when compared to the control fed-batch fermentation on average for the τ_PFR of 1 min, 2 min and 5 min were 25 %, 42 % and 46 % respectively. This indicated that the increasing the τ_PFR alone does not necessarily increase the magnitude of fermentation gradients. The new scale-down strategy developed here, increased the magnitude of fermentation gradients by not only increasing the τ_PFR, but also considering the mean frequency at which the bacterial cells entered the PFR section (f_m). The f_m was kept constant by reducing the broth volume in the STR. Hence, the bacterial cells also spent shorter times in the well mixed STR, as the τ_PFR was increased (hypothesised as giving the bacterial cells less time to recover the non-ideal PFR section of the SDR). On adoption of this strategy cadaverine productivity decreases for the τ_PFR of 1 min, 2 min and 5 min were 25 %, 32 % and 53 % respectively. Thus, highlighting that loss in performance is most likely to occur as the magnitude of heterogeneity within the fermentation environment increases. However, Corynebacterium glutamicum DM1945 Δact3 Ptuf-ldcC_OPT did show some resilience in its biomass productivity. It was only marginally affected in the harshest of conditions simulated here.