Dissertationen zum Thema „Chemical reactions monitoring“

Dissertation (Ph.D.)--Worcester Polytechnic Institute.
Keywords: Parametric optimization; nonlinear dynamics; functional equations; chemical reaction system dynamics; time scale multiplicity; robust control; nonlinear observers; invariant manifold; process monitoring; Lyapunov stability. Includes bibliographical references (leaves 92-98).

A novel method for monitoring of pharmaceutically relevant reactions using PADI-MS has been developed in this study. The visible non-thermal plasma plume from a coaxial helium gas flow non-thermal RF plasma was optimised using a range of samples. PADI-MS was found to be a powerful analytical technique for pharmaceutically relevant solid and liquid samples and can readily be adapted for use in reaction monitoring. This study has determined that PADI-MS is fast, easy to set up and requires little or no sample preparation. PADI-MS has significant advantages over other techniques as it is faster, more sensitive and more convenient and suitable for investigation of complex molecules and mixtures. However, two limitations of PADI-MS are that the plasma can affect the sample surface chemistry upon exposure and quantification is not always trivial. A number of other analytical methods were used in conjunction with PADI-MS: TLC, HPLC, FTIR and Raman spectroscopy. Chapter 3 investigated PADI-MS and Raman analysis of paracetamol tablet as model for pharmaceutically relevant solids. Raman microscopy was used to develop an understanding of how the plasma affects the sample surface. The plasma effect was also studied by examining changes in PADI-MS spectra. In Chapter 4, PADI-MS acquisition settings were improved by adding water vapour to the outer He flow gas and increasing the plasma power to 8 W, optimising the analysis of mixture solutions from TLC plates. Although molecules could be identified with optimum sensitivity after separation, this may not be necessary, unless the highest possible sensitivity is required. Chapter 5 deals with PADI-MS for direct analysis of pharmaceutical compounds in solid and liquid forms from glass slides and cotton swabs. PADI-MS was determined to besuitable for analysis of pharmaceutical tablets from solutions via both substrates, with distinct advantages for the latter. The final Chapter studied PADI-MS for the monitoring of imine formation as model pharmaceutical reaction. Both FTIR and PADI-MS were successfully used, but the latter is faster and more versatile. TLC and HPLC could not be used for this reaction. PADI-MS was successfully used for this reaction using cotton swabs without preparation or pre-concentration of sample solutions.

Several aspects of butyl acrylate/vinyl acetate (BA/VAc) polymerizations were investigated in this thesis. Polymerization process monitoring is a key factor in obtaining high quality products with prespecified properties. Therefore, a considerable part of this work was devoted to the real-time monitoring of BA/VAc emulsion polymerization reactions. An Attenuated Total Reflectance - Fourier Transform Infrared (ATR-FTIR) spectroscopy sensor was used for monitoring conversion and copolymer composition. Due to the novelty of this technique, in the first part of the study, the suitability of this technique for polymerization monitoring was investigated. In the second part of this thesis, the knowledge obtained from the off-line monitoring of the solution polymerizations was employed for the real time monitoring of six high-solids BA/VAc emulsion polymerizations. Finally, the latexes obtained in the second part of this thesis were characterized for a variety of polymer properties of interest to adhesive industry. Among the properties investigated were particle size, rheology, dynamic mechanical properties of the dry polymers and the shear and tensile strength of adhesive bonds when hard maple wood is used as a substrate. (Abstract shortened by UMI.)

Photopolymerization is the basis of several multi-million dollar industries including films and coating, inks, adhesives, fiber optics, and biomaterials. The fundamentals of the photopolymerization process, however, are not well understood. As a result, spatial variations of photopolymerization impose significant limitations on applications in which a high spatial resolution is required. To address these issues, microrheology was implemented to study the spatial and temporal effects of free-radical photopolymerization. In this work a photosensitive, acrylate resin was exposed to ultraviolet light, while the Brownian motion of micron sized, inert fluorescent tracer particles was tracked using optical videomicroscopy. Statistical analysis of particle motion yielded data that could then be used to extract rheological information about the embedding medium as a function of time and space, thereby relating UV exposure to the polymerization and gelation of monomeric resins. The effects of varying depth, initiator concentration, inhibitor concentration, composition of the monomer, and light intensity on the gelation process were studied. The most striking result is the measured difference in gelation time observed as a function of UV penetration depth. The observed trend was found to be independent of UV light intensity and monomer composition. The intensity results were used to test the accuracy of energy threshold model, which is used to empirically predict photo-induced polymerization. The results of this research affirm the ability of microrheology to provide the high spatial and temporal resolution necessary to accurately monitor the photopolymerization process. The experimental data provide a better understanding of the photo-induced polymerization, which could lead to expanded use and improved industrial process optimization. The use of microrheology to monitor photopolymerization can also aid in the development of predictive models and offer the ability to perform in-situ quality control of the process.

La spectroscopie de résonance magnétique nucléaire (RMN) est une technique amplement utilisée pour la détection et la quantification de composés chimiques avec un spectre d’application très large. Dans ce manuscrit, deux d’entre eux sont traités : la détection de polluants dans l'eau potable et la surveillance des réactions chimiques. Alors que les équipements de RMN de laboratoire présentent des résultats d'analyse très fiables, la RMN portable est un domaine de recherche en évolution avec de multiples défis technologiques et d’autres liés aux applications ciblées. Les dispositifs RMN portables émergents présentent cependant comme avantage évidente par rapport aux dispositifs classiques leur utilisation directe sur le terrain. Cela permet ainsi d’avoir des résultats d’analyses plus rapidement et de limiter les coûts de personnel et de consommables. Afin de concevoir des spectromètres RMN portables, on doit faire des compromis de conception, tout en étant capable de comprendre les enjeux liés à ces choix, afin que le produit final puisse toujours répondre aux exigences des applications concernées. Pour cela, nous proposons une chaîne d'outils de simulation RMN complète, capable de générer divers aboutissements correspondant à un spectromètre RMN réel. En outre, nous développons une preuve de concept de l’électronique de contrôle et d’acquisition basée sur des composants commerciaux disponibles et nous la validons sur notre prototype de spectromètre RMN portable. Finalement, ce prototype est utilisé pour évaluer le potentiel de la RMN portable pour les applications citées ci-dessus. Cette étude nous a permis d’identifier les limites du dispositif actuel et de proposer un cahier des charges visant son amélioration continue
Nuclear Magnetic Reaction (NMR) spectroscopy is a widely employed technique in the detection and quantification of chemical compounds, with a wide range of applications. In this manuscript, the focus is put on two of them: the detection of pollutants in drinking water and the monitoring of chemical reactions. While laboratory NMR equipment presents highly reliable analysis results, portable miniaturized NMR is an evolving research field with multiple technological and application-related challenges. Such emerging devices present however a clear advantage when compared to the classic, stablished ones: it can be used in the field, therefore saving time and limiting staff and consumables costs. In order to design NMR spectrometers to attain the desired portability and miniaturization, one has to compromise, however being able to understand what is at stake, so that the final product still meets the demands. For that, we propose a complete NMR simulation toolchain capable of generating diverse outcomes corresponding to a real NMR spectrometer. Furthermore, we develop a proof of concept for an electronic control and acquisition unit based on commercial-off-the-shelf components and validate it on a portable NMR spectrometer prototype. Finally, we use this prototype to assess the potential of portable miniaturized NMR for the targeted applications cited above. This study allowed us to identify the limits of our current prototypical device and to provide directions for its further improvement

Master of Science
Department of Chemical Engineering
J.R. Schlup
The curing reaction for the amine epoxy resin system of phenyl glycidyl ether (PGE) with metaphenylene diamine (mPDA) was investigated using two-dimensional correlation spectroscopy in the near-infared region (2DNIR). Synchronous and asynchronous correlation maps were generated using 2Dshige© software. The characteristic NIR band assignments were made, including the identification of new peaks for the O-H combination band in the 4825-4750 cm[superscript]-1 region and the CH stretching vibration overtone at 6018 cm[superscript]-1. Finally, the data suggests the reaction proceeds as follows: the appearance of the OH groups and C-H backbone vibrations occurs before the primary amine reactions and epoxide rings disappear.

Le nombre croissant de médicaments protéiques utilisés en thérapeutique a créé des besoins dans le domaine de leur quantification, principalement dans le plasma, un milieu de composition protéique complexe. Le dosage, essentiel aux études pharmacocinétique/pharmacodynamique, ainsi qu’à l’optimisation de ces traitements, est compliqué par la nature protéique de ces médicaments et par les faibles concentrations auxquelles ils sont attendus dans ces milieux complexes. La méthodologie proposée se démarque des méthodes de dosage usuelles par son caractère universel. Elle fait appel à la spectrométrie de masse adaptée à la quantification des protéines grâce à l’utilisation d’un marquage isotopique différentiel des peptides : après enrichissement et protéolyse, l’échantillon à doser est marqué sur les lysines par la version légère d’un réactif de dérivation. En parallèle, les peptides de la protéine médicament pure marqués par la version lourde du réactif, servent d’étalon interne. La possibilité de quantifier la protéine à partir de plusieurs de ses peptides améliore la fiabilité du dosage. Appliquée à l’epoetin beta aux concentrations attendues en thérapeutique (autour de 0,5 femtomole/µL de plasma), la stratégie proposée permet de situer la limite de quantification à environ 50 attomoles d’epoetin beta/µL de plasma avec une méthodologie de spectrométrie de masse nano-LC-ESI-Q-TRAP fonctionnant en mode MRM. Pour étendre l’universalité de cette approche au champ des protéines médicaments pégylées, une seconde molécule a été étudiée. Il s’agit de l’interféron alfa-2b pégylé qui a permis de mettre en place une stratégie d’extraction spécifique du médicament utilisant sa pégylation
The growing number of therapeutic proteins has created needs in the field of their quantification, mainly in plasma, which is a complex protein environment. Quantitative analysis of these proteins is essential for pharmacokinetics/pharmacodynamics studies, and for the optimization of treatments. However, the nature itself of the analyte and the low concentrations that are expected in plasma complicate the quantitative analysis. The proposed methodology differs from usual methods on its universal applicability. It relies on mass spectrometry adapted to the quantification of proteins by using peptides differential isotope labelling : after enrichment and proteolysis, the therapeutic protein and the plasmatic proteins are labelled on lysine residues by the light reagent. In parallel, peptides of the pure therapeutic protein, labelled by heavy version of reagent, are used as internal standard. The ability to quantify the protein with several of its peptides improves the reliability of the analysis. When applied to epoetin beta at expected therapeutic concentrations (about 0.5 femtomole/µL of plasma), the proposed strategy leads to a quantification limit close to 50 attomoles of epoetin beta/µL plasma, with a nano-LC-ESI-Q-TRAP mass spectrometry methodology operating in MRM. To extend the universal character of this approach to the field of pegylated protein drugs, a second therapeutic protein model has been studied. This model is a pegylated interferon alfa-2b which allowed developing a strategy for specific extraction of the drug relying on its pegylation

La maladie de Lyme, ou borréliose de Lyme, est une infection bactérienne causée par le spirochète Borrelia burgdorferi sensu lato et transmise à l'hôte (homme, animal) par piqûre de tique du genre Ixodes. Cette maladie, caractérisée par un polymorphisme clinique important, est la maladie à transmission vectorielle la plus répandue dans l'hémisphère nord. Un traitement par antibiotiques permet une guérison rapide, mais si la maladie est diagnostiquée tardivement, certains symptômes persistent. Actuellement, aucun vaccin n'est commercialisé pour l'homme. Dans ce contexte, nous avons développé des approches protéomiques afin d'apporter de nouveaux éléments de compréhension du mécanisme d'interactions de la triade tique / bactérie / hôte. Ces travaux, visant particulièrement le développement de nouvelles stratégies vaccinales et diagnostiques, sont articulés autour de trois parties : - L'identification, suite à de nombreuses optimisations, d'une méthode d'analyse HPLC-UV et nanoLC-MS/MS, de protéines présentes dans des extraits de glandes salivaires de tiques et possédant une activité sur la réponse immunitaire innée cutanée. Ces développements ont mis en évidence une liste restreinte de protéines potentiellement bioactives. - La mise au point, sur un modèle murin, d'une méthode de détection d'une protéine de Borrelia burgdorferi, OspC, dans des biopsies cutanées par spectrométrie de masse ciblée LC-SRM. Cette étude a ouvert des perspectives quant au développement de nouveaux outils diagnostiques. - L'évaluation de la faisabilité de la détection de Borrelia burgdorferi directement à la surface de la peau par imagerie par spectrométrie de masse MALDI-MSI.

Dissertação de Mestrado Integrado em Engenharia Química apresentada à Faculdade de Ciências e Tecnologia
A segurança dos pacientes e a eficácia dos medicamentos são as principais preocupações da indústria farmacêutica, para a qual a garantia da qualidade do produto é essencial.Convencionalmente, o processamento na indústria farmacêutica é realizado em regime descontínuo, sendo a qualidade dos lotes garantida através de testes laboratoriais a amostras recolhidas, por forma a monitorizar os atributos críticos de qualidade (CQAs) do produto.Contudo, ao longo dos anos, surgiram várias tecnologias que permitem maior conhecimento do produto e do processo de fabrico, possibilitando um melhor desenvolvimento, fabrico e garantia de qualidade através do controlo e da análise de dados do processo.Estas tecnologias, tecnologias analíticas de processo (PAT), utilizam instrumentação e modelação matemática para monitorizar continuamente os CQAs de um produto, permitindo a passagem de testar a qualidade do produto acabado com métodos analíticos off-line para assegurar a qualidade do produto através da monitorização contínua e em tempo real dos seus atributos.Os sensores on-line PAT fornecem a informação necessária para inferir as principais variáveis de controlo de qualidade do sistema, embora corrompida por ruídos, biases, e imprecisões de equipamento.A qualidade desta informação pode ser melhorada através da aplicação de um algoritmo de estimativa óptima, combinando as medições disponíveis com o conhecimento prévio do sistema e dos equipamentos de medição.Neste projecto, a espectroscopia de infravermelhos (IR) é utilizada para monitorizar a concentração do reagente limitante de uma reacção em tempo real.Um modelo PLS é calibrado a partir dos dados IR recolhidos para prever a concentração do reagente, e um modelo cinético para descrever o comportamento do sistema com base nos primeiros princípios é desenvolvido.Esta informação é combinada aplicando o algoritmo do filtro de Kalman estendido híbrido (HEKF).Este trabalho evidencia os resultados favoráveis da aplicação de algoritmos da família do filtro de Kalman para combinar informação resultante dos sensores e informação mecanística, que permitem obter previsões mais precisas do que as obtidas quando a mesma informação é utilizada individualmente.A aplicação do algoritmo HEKF produz uma melhoria de precisão de 50.3 % em relação ao modelo PLS, e uma melhoria de precisão de 80.0 % em relação ao modelo cinético.Esta aplicação permite também identificar o tempo final da reacção 15 minutos antes da sua ocorrência.
Patient safety and drug efficacy are the major concerns in the pharmaceutical industry, for which product quality assurance is essential.Conventionally, pharmaceutical manufacturing consists in batch processing with off-line laboratory testing conducted on collected samples to monitor the product's critical quality attributes (CQAs).However, throughout the years, several technologies with the potential to increase insight into the product and the manufacturing process have emerged, allowing for improved pharmaceutical development, manufacturing, and quality assurance through process control and analysis of process data.These technologies, process analytical technologies (PAT), employ instrumentation and mathematical modelling to continuously monitor the CQAs of a pharmaceutical product, allowing the shift from testing the quality of the finished drug product with off-line analytical methods to assuring the product’s quality by continuous, real-time monitoring of its attributes.PAT on-line sensors provide the information needed to infer key quality control variables of the system, albeit corrupted by noise, biases, and device inaccuracies.The quality of this information can be improved through application of an optimal estimation algorithm, by combining the available measurement data with prior knowledge of the system and of the measuring devices.In this project, infrared (IR) spectroscopy is used to monitor the concentration of the limiting reagent of a reaction in real-time.A PLS model is calibrated from the collected IR data to predict the concentration of the reagent and a kinetic model is developed to describe the behaviour of the system based on first principles. This information is combined applying the hybrid extended Kalman filter (HEKF) algorithm.This work evinces the favourable outcomes of applying Kalman-filter-like algorithms to combine sensor and mechanistic information, which yield predictions that are more accurate than those obtained by the same information, if individually used.The application of the HEKF algorithm yields an accuracy improvement of 50.3 % with respects to the PLS model, and an accuracy improvement of 80.0 % with respects to the kinetic model.This application also makes possible to identify the reaction's end time 15 minutes before the occurrence.

Electrospray ionization mass spectrometry (ESI-MS) is a powerful method to monitor organometallic reactions. It is fast at generating spectrum, soft to fragile organometallic compounds and sensitive to intermediates in low concentration. When coupled with the pressurized sample infusion (PSI) that helps to continuously inject reacting solution to the MS, both an inert-gas atmosphere and real-time reaction monitoring can be achieved. Also collision induced dissociation (CID) of MS can be used to probe the relative binding affinities of phosphine ligands in ruthenium complexes. PSI ESI-MS can be coupled with Fourier transform infrared spectroscopy (FTIR) to monitor the rhodium-catalyzed hydroacylation simultaneously. This technique expands the dynamic range to 5 magnitudes. The effect of mass-transfer in heterogeneous hydrogenation of charge-tagged alkyne was also studied by PSI ESI-MS. In this study cross area, stirring effect, catalyst loading and hydrogen concentration were considered and tested. Also in the study an interesting finding reveals in heterogeneity of the solution. Relative binding affinities of different phosphine ligands were attained from comparing the relative intensities of fragmentation products from MS/MS. And the phosphine ligand substitution reaction was monitored by the ESI-MS in a real-time manner. A competitive dissociative substitution mechanism was proposed and confirmed by the simulation and modeling of COPASI.
Graduate

Thesis (Ph. D.)--University of Wisconsin--Madison, 1995.
Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 246-249).

碩士
崑山科技大學
機械工程研究所
95
The chemical reactions between the frictional interfaces for the titanium specimen in the air include at least two organizations: TiN and TiO2. Moreover, the chemical mechanisms are very complex and still unclear up to now. On the other hand, it is also well known that the titanium is very widely applied in the industry. Therefore, it is worth deeply investigating the dynamic chemical reactions of the titanium specimen in the friction process. Moreover, the variations of the tribo-electrification voltage had been successfully applied to monitor the tribological properties between the metal films by our laboratory members. In fact, the novel method of using continuous tribo-electrification variations for monitoring the tribological properties between the soft metal films is more “sensitive” and “discriminative” than that by the continuous friction coefficient variations as usual. Therefore, this study is based on the above results to further develop this novel method for dynamic monitoring the chemical reactions of titanium in the friction process. The experiment was conducted by the self-developed friction tester and its measure system. The dynamic tribo-electrification and friction coefficient were measured for monitoring the chemical reactions of the titanium in the friction process. Moreover, the wear loss was measured by an accuracy balance and the SEM was used to observe the structures of material transfer after the friction test. According to the experimental results, the method of using dynamic tribo-electrification and friction coefficient variations to monitor the chemical reactions of titanium is feasible.

碩士
崑山科技大學
機械工程研究所
97
The chemical reactions between the frictional interfaces for the titanium specimen in the air include at least two organizations: TiN and TiO2. Moreover, the chemical mechanisms are very complex and still unclear up to now. On the other hand, it is also well known that the titanium is very widely applied in the industry. Therefore, it is worth deeply investigating the dynamic chemical reactions of the titanium specimen in the friction process. Moreover, the variations of the tribo-electrification voltage had been successfully applied to monitor the tribological properties between the metal films by our laboratory members. In fact, the novel method of using continuous tribo-electrification variations for monitoring the tribological properties between the soft metal films is more “sensitive” and “discriminative” than that by the continuous friction coefficient variations as usual. However, this novel method was only suitable for the conduct materials. Therefore, this study is based on the above results to further develop this novel method for dynamic monitoring the chemical reactions of titanium in the friction process. The experiment was conducted by the self-developed friction tester and its measure system. The dynamic electrical contact resistance and friction coefficient were measured for monitoring the chemical reactions of the titanium in the friction process. Moreover, the wear loss was measured by an accuracy balance and the SEM was used to observe the structures of material transfer after the friction test. According to the experimental results, the method of using dynamic electrical contact resistance and friction coefficient variations to monitor the chemical reactions of titanium is feasible.

碩士
國立交通大學
應用化學系碩博士班
101
Mass spectrometry (MS) is a powerful analytical tool that can be used to determine molecular weights and molecular structures of analytes. The progress of the ionization methods in MS is quite fast in the beginning of the 21st century because of the emerging of ambient MS (AMS). One of the advantages of AMS is that sample preparation can be minimized or eliminated. Among AMS approaches, reactive MS that can be used to monitor and to accelerate chemical reactions simultaneously during ionization process has gained considerable attentions. Furthermore, the development of reactive MS is still growing. Thus, in the first part of the thesis, an ionization method, so called ultrasonication-assisted spray ionization mass spectrometry (UASI) equipped with a miniature ultrasonic transducer (~1.7 MHz) as the ionization source was successfully used to analyze small and large molecules. Simply depositing a sample solution on the MHz-based ultrasonic transducer, which is placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Furthermore, using the UASI-MS for real-time acceleration/monitoring of chemical reactions was demonstrated. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions were readily generated and instantaneously monitored using MS within 1 s. Two reactions including Girard T reagent and hydroxylamine reacted with ketosteroids were used as the model reactions to demonstrate the feasibility of using the UASI in the applications of reactive MS. The identification of specific steroids from complex urine samples by monitoring the generation of the product ions was also demonstrated. Additionally, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has been successfully used to rapidly characterize microorganisms. Pathogenic bacteria can be identified easily based on their fingerprint mass spectra. In the second part of the thesis, an approach by combining nanoprobes, use of bleach, MALDI-MS, and principal component analysis (PCA) was proposed to rapidly identify bacteria that are different in substrain/species levels from complex samples. Fe3O4@Al2O3 MNPs were used as affinity probes to rapidly enrich a sufficient number of bacterial cells from sample solutions for MS analysis by eliminating the steps of cell culture. Followed by addition of bleach, the bleach-dissolving bacterial products were analyzed by MALDI-MS. Different species of bacteria including Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli can be readily distinguished from the resultant MALDI results combined with PCA. Furthermore, different substrains of E. coli were also able to be differentiated by this approach. Only few bacterial cells such as E. coli O157:H7 (~100 cells/mL) in complex samples can be readily characterized using this proposed method.

This thesis combines work in the areas of mass spectrometric reaction monitoring and chemical education. In the first part of this thesis, real-time mechanistic analysis using electrospray ionization mass spectrometry is reported. In Chapter 1, an introduction to the mass spectrometric instrumentation and methodologies used in this research is provided. In Chapter 2, the real-time mechanistic analysis of the Hiyama cross-coupling reaction using electrospray ionization mass spectrometry is reported, in particular, the fluoride-mediated rearrangement of phenylfluorosilanes that was found to occur even before catalyst addition. Combining Ph3SiF with a fluoride ion source under typical Hiyama cross-coupling conditions causes rapid formation of the expected [Ph3SiF2]–; however, ESI-MS analysis reveals that phenyl-fluoride exchange occurs concomitantly, also producing substantial quantities of [PhnSiF5–n]– (n = 0-2). The exchange process is verified using 19F NMR spectroscopy. This observation may have implications for Hiyama reaction protocols, which use transmetallation from triaryldifluorosilicates as a key step in cross-coupling. Optimization of the methodology used for real-time analysis by ESI-MS to reduce observed contamination from leaching of rubber septa additives is also discussed. In the second part of this thesis, the development and application of two different approaches for generating molecular models for the teaching molecular geometry and VSEPR theory in first year chemistry is reported. Chapter 4 details a method for the application of handheld 3D printing pens for producing models from ABS plastic. In Chapter 5, the development of laser-cut acrylic model kits is detailed, as well as the design and results of a quantitative study aimed at assessing their effectiveness for improving representational competence and comprehension of molecular geometry.
Graduate