Protein crystallization is significant in both biotechnology and biomedical applications. In biotechnology, crystallization is essential for determining the structure of both native and synthesized therapeutically important proteins. It can also be used as a final purification step and as a stable form for protein storage. With regard to biomedical systems, protein crystallization appears to be involved in the development and manifestation of certain human diseases. In particular, there exists evidence that L-rich ferritin crystals are involved in Hereditary Hyperferritinemia Cataract Syndrome (HHCS). In the current research a microbatch crystallization apparatus has been introduced that enables (1) multiple batch crystallization experiments at various temperatures and solution conditions in parallel and (2) quantitative monitoring of crystal growth without disturbing the progress of an experiment for observation. The primary application of the apparatus is, but not limited to, screening of protein crystallization conditions, although the system can also be used for other macromolecular and small-molecule crystallization experiments. Multiwell microbatch experiments demonstrated the dependence of apoferritin crystal growth kinetics and final crystal size on temperature and cadmium concentration. Although the solubility of apoferritin might be independent of temperature, the results of this study show that the crystal growth kinetics are affected by temperature, profoundly under some conditions. For apoferritin under near physiological conditions the solution thermodynamics in the form of the second virial coefficient have proofed to be a valuable predictor for the crystallization outcome. Furthermore, the significance of the elevated level of some divalent cations in cataractous lenses has been studied both in dilute solutions and under crystallization conditions and cadmium seems to be sole menace in apoferritin condensation.

The heat capacity and the enthalpy of crystallization of the crystalline phases at the end of cooling must be known in order to determine the excess energy of mixing two pure triglycerides, trilaurin and trimyristin, cooled at different cooling rates. The present investigation was carried out using Differential Scanning Calorimetry, DSC, Modulated Differential Scanning Calorimetry, MDSC®, and Thermal Relaxation (in a Physical Properties Measurement System, PPMS). It was found that enthalpy of crystallization values can be measured to within ? 2% (SE) with DSC Q100 TA Instruments. To achieve this, an experimental procedure and a data analysis method are proposed. It was not possible in this study to obtain accurate and reproducible heat capacity values using a DSC Q100 instrument. The values were shown to be significantly by the position of the sample pan in the measuring sensor. PPMS Cp values were within the literature values.

Batch crystallization is used widely in the production of high-value added species. It is widely recognized that product properties, some of which may be related directly to the utility of the drug, and downstream processes, such as tableting, are influenced by crystal morphology, size, and shape. The ability to observe on-line the evolution of the population density and detect a polymorphic transformation would constitute a major asset in understanding crystallizer operation and the phenomena that influence product quality. Focused-beam reflectance measurement (FBRM) is among the process analytical technologies (PAT) that hold promise for enhanced monitoring of pharmaceutical crystallization. It is based on scattering of laser light and provides a methodology for on-line monitoring of a representation of the crystal population in either batch or continuous crystallization systems. Properly installed, the FBRM allows on-line determination of the chord-length density, which is a complex function of crystal geometry and is statistically related to the population density. A model based on the geometry of the crystal was therefore established to relate both densities and thus enable computation of the population density from a measured chord length density. The evolution of the population density as a function of time leads to the estimation of the supersaturation and therefore allows the determination of the systems kinetics. From there, the population balance can be solved. Paracetamol is a common substance which exhibit polymorphism and is mainly used as an analgesic and antipyretic drug. The developed model was here applied to batch cooling crystallization of paracetamol from ethanol solutions; this system was used to explore the utility of FBRM data in detection of the polymorphic transformations. As different shapes generate different chord length densities, a transition from one polymorphic form with one specific crystal habit to another can be tracked through the FBRM. The purpose of the present study is to use the FBRM to monitor the evolution of the crystallization process, develop a model describing the evolution of the process, and monitor polymorphic transformation. The end results would be the possibility to implement a better control of the crystallization process that would ensure that downstream processing and product quality meet expectations.

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No. of bitstreams: 1 DissMMJ.pdf: 1828985 bytes, checksum: 46683e867b5c537c6e708b4cc9f3c4df (MD5) Previous issue date: 2015-04-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Brazil is the largest producer of cane sugar and the largest producer and exporter of sugar being the state of São Paulo the responsible for over 60% of the national production of sugar, and the region is where is located the city of São Carlos is main producer region of Brazil, this fact becomes a motivation for this project. The crystallization process is the most important in the production of sugar and responsible for the quality of the final product. This work deals with the modeling and simulation of this process through three different approaches: the ideal crystallizer (MSMPR), the integrated sugar production without description of crystals, approach called "gray-box", and the industrial crystallizer. The models were developed in the software EMSO. The EMSO is a program developed in Brazil and has a great advantage compared to other programs, it's a free program, without the need to license purchase. By allowing full access to the developed mathematical models, facilitates the insertion of new models such as the present study about crystallization and allow the improvement of existing models, allowing also the development of specific software libraries. The first held approach, MSMPR, aims to introduce a protocol currents description containing solids and the crystallization process in the EMSO, for in his library there is no model that describes the crystallization or even containing solids, unlike other widely used commercial programs for the simulation of processes such as Aspen Plus, having a model MSMPR. So when performing this first approach, the EMSO can match other programs in relation to the crystallization process. The mass averaged crystal size (MA) obtained with the parameters set as default, L43 = 1.18 mm is much greater than the expected value L43 = 0.5 to 0.55 mm, but with the variation of the kinetic parameters can be obtained results within the desired range . The second approach is a simplified model called "gray-box" in order to facilitate the paying in of crystallization models with models referring to others process. The sugar production obtained in this model was similar than that reported in the literature, but the model can be useful in paying in of process models which constitute a industrial plant. The third and most important approach corresponds to the model of an industrial crystalliser with intent to represent real process of sugar production using data from literature. The discussion was carried out on the variables: temperature, brix, crystal mass and MA. The variations of temperature and brix relative to time obtained are consistent with each step of the process. The crystal mass produced in the simulation is approximately 50% lower than that found in the literature, whereas the MA is also below, but achieves excellent results in the change of the kinetic parameters. The final results obtained in the simulations do not coincide with the expected results, but the easy access to developed models makes these models a good instrument to parameters analysis, reaching with some changes in the kinetic parameters, in satisfactory results that well represent the real process. / O Brasil é o maior produtor mundial de cana-de-açúcar e o maior produtor e exportador de açúcar sendo que o estado de São Paulo é responsável por mais de 60% da produção nacional de açúcar, sendo o interior paulista a principal região produtora do Brasil, tal fato torna-se uma motivação para o presente projeto, pois é onde localiza-se a cidade de São Carlos. A etapa de cristalização é a mais importante na produção de açúcar, por ser a responsável pela qualidade do produto final. O presente trabalho trata da modelagem e simulação desse processo através de três diferentes abordagens: o cristalizador ideal (MSMPR), o processo integrado de produção de açúcar sem descrição dos cristais, abordagem denominada “caixacinza”, e o cristalizador industrial. Os modelos foram desenvolvidos no software EMSO. O EMSO é um programa desenvolvido no Brasil e possui um grande diferencial em relação aos demais programas de ser de uso gratuito, sem a necessidade de compra de licença. Por possibilitar acesso total aos modelos matemáticos desenvolvidos, facilita a inserção de novos modelos, como os de cristalização do presente trabalho e permitem o aprimoramento de modelos já existentes, possibilitando, ainda, o desenvolvimento de bibliotecas específicas no software. A primeira abordagem realizada, o MSMPR, tem como objetivo introduzir um protocolo de descrição de correntes contendo sólidos e o processo de cristalização no EMSO, pois em sua biblioteca não existe nenhum modelo que descreva a cristalização ou até mesmo que contenha sólidos, diferente de outros programas comerciais muito utilizados para a simulação de processos, como o Aspen Plus, que possui um modelo de MSMPR. Então ao realizar essa primeira abordagem o EMSO pode se igualar a outros programas em relação ao processo de cristalização. O tamanho médio mássico obtido com os parâmetros estabelecidos como padrão, L43 = 1,18 mm é muito maior que o valor esperado L43 = 0,5 a 0,55 mm, porém com a variação dos parâmetros cinéticos os resultados obtidos estão na faixa desejada. A segunda abordagem trata de um modelo simplificado denominado “caixa-cinza” com o objetivo de facilitar a integralização da cristalização com modelos referentes a outros processos. A produção de açúcar obtida nesse modelo foi similar à apresentada na literatura, sendo assim, o modelo pode ser útil em uma estimativa de produção do processo e na integralização de modelos de processos que constituem uma usina. A terceira e mais importante abordagem corresponde ao modelo de um cristalizador industrial, com a intenção de representar o processo real na produção de açúcar utilizando dados provenientes da literatura. A discussão dos resultados procedeu-se sobre as variáveis: temperatura, brix, massa de cristais e tamanho médio mássico. As variações da temperatura e do brix em relação ao tempo obtidas condizem com cada etapa do processo. A massa de cristal produzida na simulação é proximadamente 50% menor do que a encontrada na literatura, enquanto que o tamanho médio também está abaixo mas atinge ótimos resultados com a alteração dos parâmetros cinéticos. Os resultados finais obtidos nas simulações não coincidiram com os resultados esperados, porém o fácil acesso aos modelos desenvolvidos torna esses modelos bons instrumentos de análises de parâmetros, podendo chegar com algumas mudanças nos parâmetros cinéticos, a resultados satisfatórios que representem bem o processo real.

Glass-ceramics are of growing interest due to their enhanced properties compared to the base glasses. More specifically, the control of microstructures is a major challenge as the properties of glass-ceramics are the direct consequences of microstructures. Microstructures can be modified by forming specific crystal phases or by using a prior amorphous phase separation before crystallization. The PhD thesis objectives are to demonstrate that the properties of silicate glasses can be enhanced by controlling their microstructure genesis with composition and thermal process parameters. More specifically, two systems were studied and compared: the BaO-TiO2-SiO2 system and the soda-lime silica Na2O-CaO-SiO2 used industrially. Both systems exhibit a large zone of immiscibility allowing the study of the influence of phase separation on crystallization.<p>The first system BaO-TiO2-SiO2 has gathered interest from the interesting properties of fresnoite (Ba2TiSi2O8): piezo and pyroelectricity, second harmonic generation and blue/white photoluminescence. Many studies on the stoichiometric composition were conducted to understand and improve those promising properties. However, it was recently suggested that the photoluminescence can be improved with composition exhibiting phase separation. This indicates that the photoluminescence intensity can be improved through a microstructural control. The possible role of a prior amorphous phase separation on the subsequent crystallization has been however the topic of vigorous debates over the last decades and has not yet been clarified, especially regarding the role of the interfaces created by the phase separation. In this PhD, the effect of phase separation on fresnoite crystallization was studied. This had to pass through the calculation of the liquid-liquid immiscibility in the phase diagram in order to select suitable compositions to compare in a systematic study. The systematic study concludes to a surface crystallization mechanism for all non- stoichiometric compositions and shows no influence between amorphous droplets and matrix crystallization. This study was also completed with the investigation of the effect of composition (i.e. SiO2-excess), annealing temperature and prior heat treatment, i.e. heating rate, cooling rate or a prior isothermal step before annealing. It is shown that specific microstructures are obtained depending on the process parameters. Finally, selected compositions and heat treatment show how photoluminescence intensity can be improved by a microstructural control. The highest intensity is obtained with a high crystallization fraction and a maximization of the number of interfaces.<p>The results obtained in the study of the BaO-TiO2-SiO2 system are extended to the soda-lime-silica system in order to study the effect of phase separation on crystallization. It is shown that cristobalite forma- tion from the surface cannot be avoided and that the involved composition shift inhibits phase separation. It is consequently difficult to observe an interplay. Those studies lead to a general discussion about the criteria allowing to observe an interplay between phase separation and crystallization in oxide glasses. / Doctorat en Sciences de l'ingénieur / info:eu-repo/semantics/nonPublished

This diploma thesis deals with crystallization additives used to modify cement composites. Describes their principle of operation, application methods and also mentions the different manufacturers with their products. In this work were made test samples with Xypex Admix crystallization additive which were tested for mechanical and physical properties depending on the amount of crystallization additives, aggressive environment and the duration of exposure in this environment. Selected samples were analyzed with RTG, DTA, SEM and porosimetry for detailed examination of the microstructure.

No description available.

We studied the usefulness of genetic fusion to TELSAM polymers as an effective protein crystallization strategy. We observed novel properties in crystals of two TELSAM-target protein fusions. TELSAM as a crystallization chaperone shows rapid crystallization when it's fused to target proteins and possibly with a greater propensity. Some TELSAM-target fusions crystallized more rapidly than the same target protein alone. TELSAM-target proteins can be crystallized at relatively low protein concentrations such as 0.1 mg/mL. TELSAM requires no TELSAM polymers touching one another in the crystal lattice in order to form well-diffracting crystals. This lack of crystal contacts has not been observed in previously reported TELSAM crystal structures. Flexible TELSAM-target protein linkers can allow target proteins to find productive binding modes against the TELSAM polymer. This study tested TELSAM linker lengths varying by the number of glycines, such as 2xGly, 4xGly, 6xGly, 8xGly, and 10xGly. Only TELSAM fused to UBA with 2 and 4 glycine linkers were crystalized. TELSAM polymers can adjust their helical rise to allow fused target proteins to make productive crystal contacts, and fusion to TELSAM polymers increases avidity to stabilize weak inter-target protein crystal contacts. In conclusion, we report features of TELSAM-target protein crystal structures and outline future work needed to validate TELSAM as a crystallization chaperone and define the best practices for its use.

No description available.

Thesis: Metal. E., Massachusetts Institute of Technology, Department of Materials Science and Engineering, 1978 / Includes bibliographical references. / Metal. E. / Metal. E. Massachusetts Institute of Technology, Department of Materials Science and Engineering