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Weber, Andreas [Verfasser]. "Process Analysis of Biosurfactant Downstream Processing / Andreas Weber." München : Verlag Dr. Hut, 2014. http://d-nb.info/1063222281/34.
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Bibi, Noor Shad [Verfasser]. "Downstream process intensification by innovative material development / Noor Shad Bibi." Bremen : IRC-Library, Information Resource Center der Jacobs University Bremen, 2012. http://d-nb.info/1035266261/34.
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Winkelnkemper, Torsten [Verfasser]. "Key performance indicators for economic downstream process development / Torsten Winkelnkemper." München : Verlag Dr. Hut, 2012. http://d-nb.info/102424279X/34.
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Hahn, Tobias [Verfasser], and J. [Akademischer Betreuer] Hubbuch. "Advances in Model-based Downstream Process Development / Tobias Hahn. Betreuer: J. Hubbuch." Karlsruhe : KIT-Bibliothek, 2015. http://d-nb.info/1081213078/34.
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Chibuye, Lweendo, and Eva Löfgren. "Performance Measurement Systems : pre-conditions & implementation process for manufacturers moving downstream." Thesis, KTH, Industriell ekonomi och organisation (Inst.), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-124522.
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Manufacturers have in recent years become more and more aware of the benefits of offering more comprehensive value propositions. As the economic climate changes, more manufacturers are trying to capture value further downstream in the value chain by providing services. The field of performance management has been extensively adopted in production and the benefits of performance measurement have been widely praised both in literature and in business. The literature on performance management has also extended into service management and how to manage service performance. But how can performance measurement and performance measurement systems be implemented when the line between products and services becomes more and more unclear? Over a twenty week period, the researchers have studied, analyzed, and observed the procedures at Scania CV’s maintenance development and delivery organization. The study was conducted on Scania’s premises in Södertälje, Sweden. Scania’s Preventative Maintenance Development group develops and sets the requirements for the preventative maintenance programs Scania offers to its customers. The group had a desire to track and measure what effects changes made in the maintenance program have on the customer’s life cycle profit. At Scania’s Preventative Maintenance Development group, there is a developed performance measurement system, MPI-model, consisting of maintenance performance indicators (MPIs). The current MPI-model, however, lacks practical applicability. The master thesis has aimed at investigating how the MPI-model could be implemented in the preventative maintenance development by researching what criteria are set in literature for performance measures, how existing resources can be employed, and how performance measurement systems can be used. Apart from conducting a case study, in order to investigate how performance measurement systems could be implemented, an extensive literature review was also conducted to provide the necessary theoretical knowledge. The result of the study was a proposed three-step model that clarifies the requirements for the implementation of a performance measurement system.
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Zheng, Yizhou. "Process development for downstream processing of human growth hormone and its antagonist." Ohio : Ohio University, 1994. http://www.ohiolink.edu/etd/view.cgi?ohiou1174330360.
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Matthey-de-l'Endroit, François. "A new downstream process for a unique lipoteichoic acid established via quantitative immunoanalysis /." [S.l.] : [s.n.], 1999. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=13536.
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Liu, Jiahong. "Downstream process synthesis for biochemical production of butanol, ethanol, and acetone from grains /." Search for this dissertation online, 2003. http://wwwlib.umi.com/cr/ksu/main.
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Johansson, Emma. "Effect of filtration aid on downstream processing of polymer particles : Effektivisering av avvattningsprocessen av polymerpartiklar." Thesis, Luleå tekniska universitet, Industriell miljö- och processteknik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-74944.
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Polymer particles are expandable and produced by Nouryon. The production consists of polymerization, dewatering and drying. Dewatering of polymer particlesis an important part of the production process and have a large impact on how efficient the downstream process can be performed. An efficient dewatering enablesa fast and effective drying process and is therefore of great importance for a fastproduction process. Here, today, there are big variations. For mostpolymer particlegradesthe dewatering aid DEW1is added to the slurry. DEW1is a non-ionic surfactant that greatly increases dewatering abilities of slurry and thus increases speedof the downstream process. But, DEW1cannotbeused for allpolymer particlegrades due to regulations. Therefore, thosepolymer particlesdemand longer downstream times with higher production costs and higher energy consumption following. The aim ofthisdiploma work was to find an alternative dewatering aid which can be used for all polymer particle grades, has a good environmental profile and increases speed of the drying process. Several compounds weretestedin laboratory scaleduring this studyto investigatetheir effect ondry contentafter dewatering.One ofthem, DEW2, showedpromising features as an alternativedewatering aid which isalso bio-based. The highestdry content ofdewatered polymer particleslurrywith DEW2as dewatering aidwasXwt% dry polymer particles.This was2.2wt% higher dry content thanthe results achieved with DEW1.Also, the effect of heated polymer particleslurry and wash water on dry content wasinvestigatedduring this study. A strong relation between higher temperatures of especially wash water and increased dry content of dewatered polymer particleswasdetected. The highest dry content achieved was Xwt% dry polymer particlesfrom a test with slurry 20 °Cand wash water 80 °C. This was an increase in dry content with 26.9 % compared to the lowest dry content achieved. The lowest value was obtained when both slurry and wash water temperature was 20 °C, which during these tests gave a dry content of Xwt%. However, polymer particlesfrom testswith high temperatures showed signs of agglomerationof polymer particles on dispersion testwhich is not accepted for polymer particles of good quality.Two full scale production trialswere performed with wash water heated to 40 °C. No agglomerated polymer particleswereseen in the dried product, and the production speed increased with 18 respectively 11 %Polymerpartiklar är expanderbara och producerade av Nouryon. Produktionen består av polymerisation, avvattning samt torkning.Avvattning avpolymerpartikelslurry är en stordel av efterbehandlingsprocessenoch det är viktigt att den kan genomföras effektivtför att minska tids-och energiåtgång. En väl fungerande avvattning främjar en snabb och effektiv torkprocess och är därför av stor betydelse för en snabb produktionsprocess. Idag finns stora variationergällande tidsåtgång beroende påvilken polymerpartikelskvalitet som produceras. Till de flesta polymerpartikelskvalitetertillsättsDEW1som fungerar somavvattningshjälpmedel. DEW1är en non-jonisk tensid som avsevärt förbättrar avvattningskapacitetenför polymerpartikelslurrynoch därmed förkortar efterbehandlingstidenoch därmed den totala produktionstiden. Dock kan inte DEW1användas föralla typer av polymerpartiklar.Det medför att produktionstidenförlängsför dessa kvaliteter, vilketleder till högre produktionskostnader samt en högre energiförbrukning. Syftet med det här examensarbetet varatt hitta ett alternativt avvattningshjälpmedelsom är miljövänligt,ökarhastigheten på avvattning-och torkningsprocessenoch som kan användas för alla typer av polymerpartiklar. Ett antal substansertestadesunder examensarbetet laborativt för att utvärdera deras effekt påtorrhalt på polymerpartiklarefter avvattning. Det biobaseradeavvattningshjälpmedlet DEW2såglovande ut med goda avvattningsegenskaper. Resultaten från försök med DEW2gav2.2wt% högre torrhaltän DEW1. Andra försök gjordes under examensarbetetför att undersöka sambandet mellan temperatur på polymerpartikelslurryoch tvättvatten mot torrhalt på avvattnade polymerpartiklar. Högre temperatur på speciellt tvättvatten gavhögre torrhalt, och den högsta torrhalten som uppnåddes vid försöken varXwt%med en slurrytemperatur på 20 °Coch tvättvattentemperatur på80 °C.Jämfört med det sämsta resultatet för torrhalt var det en ökningmed26.9%mot resultatet från tester utförda med slurry och tvättvattentemperatur 20 °C, som gav torrhalten Xwt%. Dessvärre visadedispersionstesterfrån testerutförda med temperaturer mellan 50 till 80 °Catt agglomerat bildatsi torkade polymerpartiklar.Två produktionstester utfördes där tvättvattnet värmdes till 40 °C. Här sågs inga problem med agglomerat i färdig produktoch produktionshastigheten ökade med 18 respektive 11 %.
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Thygs, Fabian B. [Verfasser]. "Automation Techniques to Support Experimental Investigation During Systematic Downstream Process Development / Fabian B. Thygs." München : Verlag Dr. Hut, 2017. http://d-nb.info/1149580240/34.
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Wang, Gang [Verfasser], and J. [Akademischer Betreuer] Hubbuch. "Advancing Downstream Process Development - Mechanistic Modeling and Artificial Intelligence / Gang Wang ; Betreuer: J. Hubbuch." Karlsruhe : KIT-Bibliothek, 2018. http://d-nb.info/1163320358/34.
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Horn, Carsten. "Downstream processing with affinity chromatography : a study of a continuous process for biospecific adsorption." Thesis, University of South Wales, 1993. https://pure.southwales.ac.uk/en/studentthesis/downstream-processing-with-affinity-chromatography-a-study-of-a-continuous-process-for-biospecific-adsorption(acd33b1a-fed5-47b3-9b01-b389810c1466).html.
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A polymer matrix of hydroxy ethyl methacrylate - ethylene glycol dimethacrylate was synthesised and coupled with the ligand p-aminobenzamidine. Although the adsorbent displayed sufficient affinity towards trypsin, the overall adsorption performance was not satisfactory. Subsequent studies were carried out with a p-aminobenzamidine silica adsorbent, which gave far superior results. Amounts of up to 35 mg of trypsin per g of silica could be adsorbed from a porcine pancreatic extract at buffer conditions of 0.05 M Tris, 0.5 M NaCl, pH 8. Complete elution was achieved with a buffer of 0.1 M acetic acid, pH 3. The system was characterised by fixed bed breakthrough studies of the adsorption, wash and desorption step. A method of data analysis was developed and applied to the experimental results. Axial dispersion could be identified as the predominant 'mass transfer' mechanism. A simulation model was build, based on the data analysis results. The model was verified successfully against the experimental data. Continuous separation experiments were performed with three fluidised beds, namely an adsorption, desorption and wash column, with circulation of solids between the columns. Purities of 83% and 66% were achieved in these runs with complete recovery of trypsin. A continuous process model, also based on the data analysis results and on fluidised bed characteristics, was found to agree fairly well with the experimental data. Simulation experiments were conducted to find the optimum configuration of the process. Best performances with respect to product purity were obtained for an adsorption column height of 3 cm and a wash column height of 4 cm. Step experiments revealed that the process is relatively easy to control if the solid flow rate is chosen as the control parameter.
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Hadjiyiannis, Constantinos. "Investigation of break-up process of liquids and downstream spray characteristics in air-blast atomisers." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/23215.
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The research of this thesis focuses on the study of sprays produced by twin fluid air-blast atomisers and the main objective is to study the liquid jet break-up mechanism and relate it to the downstream spray characteristics. Two different air-blast atomiser geometries are used; coaxial, where the liquid co-flows with the gas stream, and the liquid jet in a gaseous cross-flow. The thesis describes advanced and novel measurements to reveal the temporal and spatial development of the liquid flow and its interaction with the surrounding gas stream. Initially, the break-up process is studied by measuring the characteristics of the continuous liquid jet. Techniques such as electrical conductivity, high-speed shadowgraphy and optical connectivity were used to characterise the atomisation process. The latter is a novel laser-based technique used to illuminate internally the continuous liquid column by introducing a laser beam within the liquid nozzle, while a fluorescent dye in the liquid ensures that the whole volume of the liquid is visualised. The laser light propagates downstream while reflecting on the gas-liquid interface to be interrupted at the break-up position, where the light is scattered and diffuses widely. In the case of a jet in a cross-flow gas stream the fluorescent intensity images were recorded from two different angles to reveal the various features involved in the liquid jet structure. The study of the spatial and temporal characteristics of the instabilities and the developed surface waves on the liquid column can provide information on jet morphology and a better understanding of the physics that elicit the break-up phenomenon. For that purpose, Proper Orthogonal Decomposition (POD) is applied to reveal the various flow scales and elucidate the mechanism of transfer of momentum from the gas to the liquid flow. The most energetic modes are used to describe the jet interface dynamics that may well define the formation of the downstream droplet sizes. Interferometric Laser Imaging for Droplet Sizing (ILIDS) was also used for planar measurements of droplet sizes and velocities. ILIDS images the scattered light from droplets in an out-of-focus mode at different streamwise distances from the nozzle exit to obtain interference fringe patterns associated with each droplet. The spacing of each fringe pattern is proportional to the corresponding droplet diameter. Instantaneous droplet clustering is measured along with the primary atomisation process and the liquid jet break-up characteristics are correlated with the downstream droplet sizes. Several time delays are used between optical connectivity and ILIDS measurements to capture the various classes of droplet sizes that travel with different velocities from the break-up region to the downstream spray location. The small droplets travel faster and move with a velocity similar to the gas flow, in contrast to the larger droplets, which are conveyed to the size measuring region with a lower velocity and, therefore, higher time delays. A conditional correlation method was developed to reduce statistical uncertainties. Negative correlations were found between the break-up length of the liquid jet and downstream number of droplets, indicating that they are inversely proportional. The relation between the break-up length and droplet Arithmetic and Sauter Mean Diameters seems to be more complex since a sinusoidal relation was extracted. The estimated correlation coefficients varied with time delay and a repeatable trend was observed which exposed the coherent behaviour of the break-up process and its frequency, revealing that it is not a random phenomenon, but rather a multifaceted mechanism governed by physical laws.
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Vicente, Tiago. "Downstream processing development of enveloped viruses for clinical applications: innovative tools for rational process optimization." Doctoral thesis, Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica, 2010. http://hdl.handle.net/10362/5247.
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Dissertation presented to obtain a Ph.D. degree in Engineering and Technology
Sciences, Biotechnology at the Instituto de Tecnologia Química e Biológica,
Universidade Nova de LisboaViral vectors and virus-like particles hold a tremendous potential in various clinical applications in the areas of gene therapy and/or vaccination, drawing the attention of biotechnology and pharmaceutical companies. The majority of these products are manufactured in animal cell cultures, inherently making the process costly. A great deal of effort is taking place to generate optimized biological and engineering strategies to find scalable and cost-effective processes, easily transferable to cGMP facilities. However, the implementation of robust downstream processes generating this type of biopharmaceuticals in the amounts required for pre-clinical and clinical trials is still lacking and lagging. By including a labile lipid membrane layer harboring glycoproteins (often critical for infection) over the viral capsid, enveloped viruses bring extra challenges in terms of their bioprocessing particularly downstream. The work developed during this thesis aimed at improving the state-of-the-art purification processes for these types of viral particles. The rationale was to integrate process understanding with product characterization, still scarce in such biological systems.(...)
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Norouzi, Saba. "Measuring Iranian Petroleum Downstream Supply Chain Management Performance; : A Combination of Analytical Hierarchy Process and Balance Score Card." Thesis, KTH, Industriell produktion, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-128168.
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Petroleum downstream is a strategic and important industry for any nation. It supplies most of transport and travel needs and provides petrochemical business raw material, which is one of the infrastructure industries. Considering the importance of petroleum downstream and due to a very volatile crude and product market, one of the industry’s main targets is to meet customers’ requirements with administrating downstream supply chain efficiently. Supply chain management (SCM) is a strategic tool to enhance an organization’s productivity, profitability and certifying the success of business. Performance of SCM can indicate how successfully the supply chain is able to deal with its aim, which is increasing profit by increasing value to the customer. For evaluating the performance of SCM, a measurement system is required to determine its progress toward the main goal. In this thesis, the main concern is to propose a performance measurement method which is applicable for petroleum downstream SCM. For this purpose literature review is used to develop a model in Iran petroleum downstream. As a result of the research a numerical performance measurement model is suggested for Iranian downstream petroleum industry which is a combination of Analytical Hierarchy Process (AHP) and Balance Score card (BSC). One of the main features of this model is that it is applicable for industry level and can be used for benchmarking one SCM against another. Key words: Supply chain management, Performance measurement, Petroleum downstream supply chain, Balance score card, Analytical hierarchy process.
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Grossi, Matteo. "Dynamic design, optimization and simulation of a control strategy for a pharmaceutical bioprocess." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/17906/.
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In recent years, pharmaceutical companies have grown interest in developing new technologies for the continuous manufacturing of drug products. The continuous manufacturing of pharmaceuticals is critical in order to increase productivity and to reduce the amount of overall waste in a time-efficient manner. To strive towards this goal, in this work, the realistic case study of the continuous production of lovastatin is investigated and modeled. Therefore, based on the steady-state model proposed by Colombo et al. (2018) [1], a control plant-wide control strategy is developed and simulated for a semi-continuous benchmark simulation model for the production of lovastatin. Hence, the upstream and downstream processes have been integrated with feedback control systems using rigorous non-linear dynamic process models, in order to reach an accurate control of the process variables, and thus consistently maintain the predefined product quality. The proposed strategy ultimately leads to the identification and the development of a comprehensive benchmark model of an end-to-end plant-wide controlled system that, as it captures the generic dynamics of a bio-pharmaceutical process, can be deemed as a starting point for further simulations and implementations of other chemical process units. The results showed that under considerable and durable disturbances, the designed control strategy is capable to take action and adjust the process variables to their set points values, thus attesting for the effectiveness of the proposed model.
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Han, Tzu-Chiang. "Control of Intein-Mediated Self-Cleaving Tag for Recombinant Protein Purification." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1453206997.
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Neal, G. E. "Integrated scale down of the primary downstream purification process and assessment of alternative process options for the production of an ovine polyclonal antibody based anti-venom." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444864/.
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This thesis describes the development of a linked 1000th scale mimic of four distinct unit operations, including precipitation and centrifugation. These operations are utilised during the production of an anti-snake venom Fab fragment. A new approach has been used to define the important engineering parameters that impacted on the recovery process the effect of these was verified by experimental work. The mimic requires only millilitre quantities of material to predict changes in the physical and biological properties of key components, such as particle size and antibody activity. The potential impact of several process changes on the characteristics of the feed stream and on purification steps further downstream has been assessed, which is not possible without a linked system. Microfiltration has been examined as a possible alternative to the current centrifugal method of recovering the antibody particles. A small-scale stirred cell device was used to carry out a number of operations in a single piece of equipment these included separation, concentration and buffer exchange. An overall increase in the yield of 10% was observed. This was attributed to the ability of microfiltration to reduce material losses by integrating a number of operations. A preliminary investigation has been conducted into the possibility of utilising Protein G affinity chromatography in place of the current four-step precipitation and centrifugation recovery operation. A mathematical model capable of predicting the size and shape of the breakthrough curves has been developed the predicted curves were tested by comparison with breakthrough curves produced under different experimental conditions. The initial results demonstrated the feasibility of utilising affinity chromatography as a one step recovery process. However the predicted breakthrough curves varied from the experimental curves suggesting that the mathematical model requires refinement.
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Oppermann, Tobias [Verfasser]. "Mannheimia haemolytica – Bioprocess improvement of leukotoxin production using a fed-batch process and a ceramic membrane based downstream strategy / Tobias Oppermann." Aachen : Shaker, 2018. http://d-nb.info/1188549286/34.
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Gorte, Olga [Verfasser], and C. [Akademischer Betreuer] Syldatk. "Towards an optimized lipid production with unconventional oleaginous yeasts - Process optimization and evaluation of lipid downstream methods / Olga Gorte ; Betreuer: C. Syldatk." Karlsruhe : KIT-Bibliothek, 2021. http://d-nb.info/1233359088/34.
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Heathman, Thomas R. J. "Developing a process control strategy for the consistent and scalable manufacture of human mesenchymal stem cells." Thesis, Loughborough University, 2015. https://dspace.lboro.ac.uk/2134/22174.
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Human mesenchymal stem cells (hMSCs) have been identified as a promising cell-based therapy candidate to treat a number of unmet clinical indications, however, in vitro expansion will be required to increase the available number of cells and meet this demand. Scalable manufacturing processes, amenable to closed, single-use and automated technology, must therefore be developed in order to produce safe, effective and affordable hMSC therapies. To address this challenge, a controlled serum-free end-to-end microcarrier process has been developed for hMSCs, which is amenable to large-scale manufacture and therefore increasing economies of scale. Preliminary studies in monolayer culture assessed the level of variability in growth between five hMSC donors, which was found to have a variance of 25.3 % after 30 days in culture. This variance was subsequently reduced to 4.5% by the development of a serum-free monolayer culture process with the maintenance of critical hMSC characteristics and an increased number of population doublings. In order to transfer this into a scalable system, the serum and serum-free expansion processes were transferred into suspension by the addition of plastic microcarriers in 100 mL spinner flasks without control of pH or dissolved oxygen (DO). This achieved a maximum cell density of 0.08 ± 0.01 · 106 cells.mL-1 in FBS-based medium, 0.12 ± 0.01 · 106 cells.mL-1 in HPL-based medium and 0.27 ± 0.03 · 106 cells.mL-1 in serum free medium after six days. In order to drive consistency and yield into the manufacturing process, a process control system was developed for the FBS-based microcarrier expansion process in a 100 mL DASbox bioreactor platform to control DO, pH, impeller rate and temperature. Reduced impeller rates and DO concentrations were found to be beneficial, with a final cell density of 0.11 ± 0.02 · 106 cells.mL-1 and improved post-harvest outgrowth and colony-forming unit (CFU) potential compared to uncontrolled microcarrier and monolayer culture. This controlled bioreactor expansion process was then applied to the previously developed serum-free microcarrier process, eventually achieving a final cell density of 1.04 ± 0.07 · 106 cells.mL-1, whilst retaining key post-harvest hMSC characteristics. Following the controlled serum-free expansion and harvest of hMSCs, a downstream and cryopreservation process was developed to assess the impact of prolonged holding times and subsequent unit-operations on hMSC quality characteristics. This showed that hMSCs are able to maintain key characteristics throughout the entire end-to-end process, demonstrating their potential for commercial scale manufacture.
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Zhang, Jian. "Advance Surgery Scheduling with Consideration of Downstream Capacity Constraints and Multiple Sources of Uncertainty." Thesis, Bourgogne Franche-Comté, 2019. http://www.theses.fr/2019UBFCA023.
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Les travaux de ce mémoire portent sur une gestion optimisée des blocs opératoires dans un service chirurgical. Les arrivées des patients chaque semaine, la durée des opérations et les temps de séjour des patients sont considérés comme des paramètres assujettis à des incertitudes. Chaque semaine, le gestionnaire hospitalier doit déterminer les blocs chirurgicaux à mettre en service et leur affecter certaines opérations figurant sur la liste d'attente. L'objectif est la minimisation d'une part des coûts liés à la réalisation et au report des opérations, et d'autre part des coûts hospitaliers liés aux ressources chirurgicaux. Lorsque nous considérons que les modèles de programmations mathématiques couramment utilisés dans la littérature n'optimisent pas la performance à long terme des programmes chirurgicaux, nous proposons un nouveau modèle d'optimisation à deux phases combinant le processus de décision Markovien (MDP) et la programmation stochastique. Le MDP de la première phase détermine les opérations à effectuer chaque semaine et minimise les coûts totaux sur un horizon infini. La programmation stochastique de la deuxième phase optimise les affectations des opérations sélectionnées dans les blocs chirurgicaux. Afin de résoudre la complexité des problèmes de grande taille, nous développons un algorithme de programmation dynamique approximatif basé sur l'apprentissage par renforcement et plusieurs autres heuristiques basés sur la génération de colonnes. Nous développons des applications numériques afin d'évaluer le modèle et les algorithmes proposés. Les résultats expérimentaux indiquent que ces algorithmes sont considérablement plus efficaces que les algorithmes traditionnels. Les programmes chirurgicaux du modèle d’optimisation à deux phases sont plus performants de manière significative que ceux d’un modèle de programmation stochastique classique en termes de temps d’attente des patients et de coûts totaux sur le long termeThis thesis deals with the advance scheduling of elective surgeries in an operating theatre that is composed of operating rooms and downstream recovery units. The arrivals of new patients in each week, the duration of each surgery, and the length-of-stay of each patient in the downstream recovery unit are subject to uncertainty. In each week, the surgery planner should determine the surgical blocks to open and assign some of the surgeries in the waiting list to the open surgical blocks. The objective is to minimize the patient-related costs incurred by performing and postponing surgeries as well as the hospital-related costs caused by the utilization of surgical resources. Considering that the pure mathematical programming models commonly used in literature do not optimize the long-term performance of the surgery schedules, we propose a novel two-phase optimization model that combines Markov decision process (MDP) and stochastic programming to overcome this drawback. The MDP model in the first phase determines the surgeries to be performed in each week and minimizes the expected total costs over an infinite horizon, then the stochastic programming model in the second phase optimizes the assignments of the selected surgeries to surgical blocks. In order to cope with the huge complexity of realistically sized problems, we develop a reinforcement-learning-based approximate dynamic programming algorithm and several column-generation-based heuristic algorithms as the solution approaches. We conduct numerical experiments to evaluate the model and algorithms proposed in this thesis. The experimental results indicate that the proposed algorithms are considerably more efficient than the traditional ones, and that the resulting schedules of the two-phase optimization model significantly outperform those of a conventional stochastic programming model in terms of the patients' waiting times and the total costs on the long run
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Kornecki, Martin Lukas [Verfasser], Jochen [Akademischer Betreuer] Strube, and Udo [Akademischer Betreuer] Rau. "Methoden zur Integration von Upstream und Downstream Processing für Biologics hinsichtlich Prozessentwicklung, Digital Twin und Process Analytical Technology / Martin Lukas Kornecki ; Jochen Strube, Udo Rau." Clausthal-Zellerfeld : Technische Universität Clausthal, 2020. http://d-nb.info/1231362537/34.
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Neumann, Gregor [Verfasser], and Hans-Georg [Akademischer Betreuer] Rammensee. "Downstream process development and preliminary formulation development for the bispecific antibody NF-CU N297Q for a clinical phase I/IIa trial / Gregor Neumann ; Betreuer: Hans-Georg Rammensee." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/1197694196/34.
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Zimmermann, Sarah [Verfasser], and J. [Akademischer Betreuer] Hubbuch. "Cell Separation in Aqueous Two-Phase Systems - Development of an Integrated High-Throughput Screening Platform for Downstream Process Development for Cell-Based Products / Sarah Zimmermann ; Betreuer: J. Hubbuch." Karlsruhe : KIT-Bibliothek, 2017. http://d-nb.info/1130246558/34.
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Masri, Mahmoud [Verfasser], Thomas [Akademischer Betreuer] Brück, Thomas [Gutachter] Brück, Rainer [Gutachter] Buchholz, and Volker [Gutachter] Sieber. "Generation of Microbial Oil via a Process Engineering Approach : New generation of up- /downstream processing and a feedstock / Mahmoud Masri ; Gutachter: Thomas Brück, Rainer Buchholz, Volker Sieber ; Betreuer: Thomas Brück." München : Universitätsbibliothek der TU München, 2019. http://d-nb.info/1202111289/34.
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Orlando, Anna Chiara. "Recupero e purificazione di poliidrossialcanoati da cellule batteriche." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amslaurea.unibo.it/9070/.
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Le materie plastiche sono materiali polimerici che possono contenere altre sostanze finalizzate a migliorarne le proprietà o ridurre i costi (IUPAC).
Accanto agli innumerevoli vantaggi apportati dall’utilizzo della plastica, negli anni sono emersi aspetti negativi relativi all’inquinamento ambientale causato dalla dispersione del materiale plastico nei rifiuti urbani e conseguentemente nelle discariche.
La diffusione e l’utilizzo della bioplastica si pone come obiettivo minimizzare la dipendenza dal petrolio in previsione della diminuzione del numero di giacimenti e quindi della sua disponibilità.
Lo scopo del presente lavoro di sperimentazione è lo studio del processo di dowstream di PHA prodotti in laboratorio partendo dalla verifica dei risultati riportati in letteratura e puntando poi ad un miglioramento di un processo convenzionale attraverso la ricerca di nuove alternative.
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Di, Nuzzo Nicola. "Use of recycled polystyrene to manufacture filtration membranes: an experimental investigation." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amslaurea.unibo.it/22395/.
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This study has the aim to investigate the possibility to use recycled polystyrene (PS) as feedstock for the preparation of membranes. Considering that recycling is becoming a consolidated reality, it is fundamental to explore other possibilities and see if a recycled material can substitute a conventional product. Moreover, it is relevant to understand which are the advantages and limitations of this new approach, to define the possible applications on actual processes.
In particular, the goal is to produce a reliable membrane, with a narrow pore size distribution, that should be suitable for filtration applications, considering that membranes made of recycled polymers are a developing field and that polystyrene is not commonly used for membrane production, due to its hydrophobicity and due to its fragility when casted.
Using the E.T.E. technology (Emulsified Thermoplastic Engineering) it is possible to obtain recycled PS from food packaging, which was then used for the membrane production by phase inversion, along with NaCl and several types of PEG as porogens.
The samples are then tested to evaluate their properties in terms of permeability, porosity and rejection, to understand the suitability of this material and to possibly define an application.
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Banaszewski, Roni Fabio. "Modelo multiagentes baseado em um protocolo de leilões simultâneos para aplicação no problema de planejamento de transferências de produtos no segmento downstream do sistema logístico brasileiro de petróleo." Universidade Tecnológica Federal do Paraná, 2014. http://repositorio.utfpr.edu.br/jspui/handle/1/822.
Full textAbstract:
CAPESO segmento downstream da cadeia de suprimentos da indústria brasileira de petróleo é composta por bases de produção (e.g. refinarias), armazenamento (e.g. terminais) e consumo (e.g. mercados consumidores) e modais de transportes (e.g. oleodutos, navios, caminhões e trens). O planejamento da transferência de derivados de petróleo nesta rede multimodal é um problema complexo e atualmente é realizado para um horizonte de três meses com base na experiência de profissionais e sem auxílio de um sistema computacional de apoio à decisão. Basicamente, o problema pode ser visto como uma negociação para alocação de recursos disponíveis (tais como derivados de petróleo, tanques e modais de transporte) pelas diferentes bases envolvidas que necessitam enviar ou receber derivados de petróleo. Na literatura, alguns problemas semelhantes, porém mais voltados para o planejamento de redes formadas por um único tipo de modal de transporte, têm sido tratados por diferentes abordagens, com predominância da programação matemática. Estes trabalhos ilustram a difícil tarefa de modelar grandes problemas por meio desta abordagem. Geralmente, tais trabalhos consideram apenas um curto horizonte de planejamento ou apenas uma parte do problema original, tal como uma parte da rede petrolífera brasileira, gerando limitações importantes para os modelos desenvolvidos. Devido às características do problema em estudo, o qual envolve toda a rede de transporte e apresenta perfil de negociação entre as diferentes entidades envolvidas, surge o interesse da utilização do paradigma de sistemas multiagente. O paradigma de agentes tem sido aplicado a problemas de diferentes contextos, particularmente em problemas de gerenciamento de cadeias de suprimentos devido à sua correspondência natural com a realidade e, em geral, em problemas que envolvem a competição por recursos por meio de mecanismos de negociação com base em leilões. Este trabalho apresenta um novo protocolo de negociação baseado em leilões e aplicação deste protocolo em forma de um modelo multiagente na resolução do problema de planejamento em questão. Os agentes que formam a solução representam principalmente os locais de produção, armazenamento, consumo e os modais de transporte na rede petrolífera brasileira. O objetivo destes agentes é manter um nível de estoque diário factível de cada produto em cada local por meio de transferências de produtos pela rede petrolífera brasileira com preferível redução do custo de transporte. Por fim, este trabalho apresenta a satisfação destes objetivos por meio de experimentos em cenários fictícios e reais da rede brasileira de petróleo.
The Brazilian oil supply chain is composed by oil refineries, consumer markets, terminals for intermediary storage and several transportation modals, such as pipelines, ships, trucks and trains. The transportation planning of oil products in this multimodal network is a complex problem that is currently performed manually based on expertise, for a period of three months, due to the lack of a software system to cover the problem complexity. Such problem involves the negotiation of available resources such as oil products, tanks and transportation modals between different sources and consumption points. Similar problems, but more directed to the planning of single modes of transportation, have been treated by different approaches, mainly mathematical programming. Such works illustrate the difficult task of modeling large problems with this mechanism. Generally, they consider a short horizon planning or only part of the original problem, such as a part of the network, rendering important limitations to the models developed. Due to the characteristics of the problem in study where the full network needs to be considered and there exists negotiation amongst the different entities involved, the usage of multi-agent models seems to be worth to explore. Such models have been applied in different contexts such as to supply chain problems due its natural correspondence with the reality. Furthermore, in problems involving competition for resources, multi-agents negotiation mechanisms based on auctions are commonly applied. Thus, this thesis presents one auction-based solution formed by the cooperation among agents for them to achieve their goals. The agents involved in the auctions represent mainly the production, storage and consumption locations. Their goal is to maintain a daily suitable inventory level for each product by means of transportation through the multimodal network at a low transport cost. Finally, this paper presents the satisfaction of these objectives through experiments on real and fictional scenarios of Brazilian oil network.
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Moreira, Ana Sofia da Costa. "Downstream process development of novel valuable bio-therapeutics." Master's thesis, 2016. http://hdl.handle.net/10316/36427.
Full textAbstract:
Dissertação de mestrado em Biotecnologia Farmacêutica, apresentada à Faculdade de Farmácia da Universidade de CoimbraThe development of novel recombinant Virus-like particles (VLPS) has been putting the spotlight in vaccine’s biomanufacturing. However, establishing purification and quantification methods for complex therapeutic products with a short time to market represents an engineering challenge. The first aim of this work was to use BLI technology to improve mucin detection and quantification in a fast, simple and label free way. The experiments were performed using streptavidin (SAX) biosensors that binds biotinylated lectins, which can recognize mucins carbohydrate structures. Two different mucins were detected and quantified: Bovine Submaxillary Gland Mucin (BSM) and human MUC5B mucin. Different assay conditions were optimized and the most suitable lectin, Aleuria aurantia lectin (AAL), was selected. Additionally, competition assay allowed the identification of the minimal concentration to inhibit AAL-mucin association. These results can be applied for future mucin purification improvement, for example, in affinity chromatography. The second part of this work reports the development and implementation of a flow-through purification strategy for Hepatitis C virus-like particles, using anion exchange chromatography. Exploratory evaluations were performed using scale-down tools, in one mL scout column. The results obtained allowed the translation to radial flow chromatography, an alternative to standard axial packed columns. The global recovery yield of the developed strategy was 66%. Impurity clearance efficiencies with a log reduction value of 2 and 1.4 for baculovirus and DNA, were achieved. Overall, valuable tools were reported and can be used to improved and optimized new and already established purification processes.
O desenvolvimento de novas partículas recombinantes semelhante a vírus (VLPs) tem colocado grande foco na produção de vacinas. Contudo, implementar métodos de purificação e quantificação para produtos terapêuticos complexos, de forma a entrarem rapidamente no mercado, representa um desafio significativo. O primeiro objetivo deste trabalho foi utilizar a tecnologia de Bio-layer interferometry (BLI) de modo a melhorar a deteção e quantificação de mucinas, de uma forma rápida, simples e sem recorrer ao uso de marcadores. O método foi implementado com recuso a biossensores de streptavidina (SAX), com afinidade para lectinas biotiniladas, que são capazes de reconhecer estruturas de hidratos de carbono existentes nas mucinas. Foram avaliadas, deteção e quantificação, duas mucinas distintas: a mucina da glândula submaxiliar bovina (BSM) e a mucina humana MUC5B. Depois de otimizadas diferentes condições foi selecionada a lectina mais adequada, Aleuria aurantia lectina (AAL). Adicionalmente, ensaios de competição permitiram a identificação da concentração mínima para inibir a associação AAL-mucina. Estes resultados podem ser aplicados futuramente, nomeadamente para otimizar a purificação de mucinas, por exemplo, em cromatografia de afinidade. A segunda parte deste trabalho descreve o desenvolvimento e implementação de uma estratégia de purificação por cromatografia em modo negativo para VLPs de Hepatite C, recorrendo a cromatografia de troca aniónica. Foram realizadas avaliações com o uso de materiais para escalas laboratoriais, em colunas de um mL. Os resultados obtidos permitiram a transição para cromatografia de fluxo radial, que representa uma alternativa às colunas tradicionais de fluxo axial. A percentagem da recuperação global do método desenvolvido foi de 66%. Quanto à remoção de impurezas foram obtidos log reduction values de 2 para baculovírus e 1.4 para DNA. No geral, foram referidas neste trabalho ferramentas de grande valor que podem ser utilizadas para melhorar e otimizar métodos de purificação novos e já existentes.
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Ferreira, Hugo Miguel Lambuça. "Overcome challenges in influenza virus-like particles downstream process." Master's thesis, 2017. http://hdl.handle.net/10362/24817.
Full textAbstract:
The development of new vaccines for influenza virus introduced a new generation of vaccines using virus-like particles (VLPs). The lack of genetic material, possibility of production on cell lines and presence of antigens with immunogenicity are the main advantages over the traditional vaccines. The development of a cost-effective downstream process while maintaining the high purity, potency and quality of VLPs is a challenge. In this thesis, several purification steps – clarification, concentration, chromatography, polishing and sterile filtration – were studied to develop a new downstream proves for influenza VLPs.
In clarification step, a strategy using D0HC followed by Opticap XL SHC filters presented the best result. For concentration step, the cassette with cut-off of 300 kDa presented a higher yield on hemagglutinin recovery and the lowest process time. For chromatography step, the membrane Sartobind Q and the resin HiTrap Q HP were evaluated, concluding that resin HiTrap presented higher dynamic binding capacity and better resolution on elution. For polishing step, size-exclusion chromatography and multimodal chromatography operate in flow-through mode were compared. The last presented higher recovery yield on hemagglutinin and it was select due to the non-limitation for scale-up. Different materials were analysed for the final sterile filtration.
A proof of concept run was performed were the optimized conditions and best devices were evaluated. In the end of process, it was obtained influenza VLPs with concentration and quality enough to advance for animal in vivo studies and for clinical phase I.
Additionally, a new tool – magnetic sulphated cellulose particles – was evaluated with the goal to obtain purified and concentrated samples to use in characterization techniques.
Overall, this thesis contributes to introduce a new tool and a novel cost-effective downstream purification process with high purity, potency and quality for the next generation of influenza vaccines - VLPs.O desenvolvimento de novas vacinas para o vírus de influenza introduziu uma nova geração de vacinas utilizando partículas semelhantes a vírus (VLPs). A ausência de material genético, possibilidade de produção em linhas celulares e presença de antigénios com imunogenicidade são as principais vantagens em relação às vacinas tradicionais. O desenvolvimento de um processo de purificação de baixo custo mantendo a elevada pureza, potencia e qualidade das VLPs é um desafio. Nesta tese, alguns passos de purificação – clarificação, concentração, cromatografia, polimento e filtração estéril final – foram estudados para desenvolver um novo processo de purificação de VLPs de influenza. Na clarificação, a estratégia usando os filtros D0HC seguido do Opticap XL SHC apresentaram os melhores resultados. Na concentração, a cassete com cut-off de 300 kDa apresentou um maior rendimento na recuperação de hemaglutinina e o mais baixo tempo de operação. Na cromatografia, a membrana Sartobind Q e a resina HiTrap Q HP foram avaliadas, concluindo-se que a resina apresenta maior capacidade de ligação dinâmica e maior resolução na eluição. No polimento, a cromatografia de exclusão molecular e a cromatografia multimodal, operada em flow-through comparadas. Esta última apresentou valores superiores de recuperação de hemaglutinina sendo escolhida por não conter limitações no escalamento. Diferentes materiais foram analisados na filtração estéril final. Na realização da corrida de prova de conceito as condições ótimas e os melhores materiais foram estudadas. No final do processo, obteve-se VLPs de influenza na concentração e qualidade suficiente para avançar para estudos em animais in vivo e para fase clínica I. Adicionalmente, uma nova ferramenta – partículas magnéticas de celulose sulfatada – foram estudadas com objetivo de obter VLPs purificadas e concentradas para utilização em técnicas de caracterização. Em geral, esta tese contribuiu para introduzir uma nova ferramenta e um novo processo de purificação mais económico com elevada pureza, potência e qualidade, para a nova geração de vacinas - VLPs.
iBET
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Vaz, Bárbara Maria Correia. "Development of downstream processes for pigment valorization: a step towards blue biorefinery." Master's thesis, 2021. http://hdl.handle.net/10773/33018.
Full textAbstract:
The guidelines of The 2030 Agenda for Sustainable Development were very clear. New strategies need to be found to ensure a sustainable future. In this way, marine resources emerge as natural and renewable feedstocks to integrate a blue biorefinery framework and a circular economy approach. Through biomass conversion an integrated production of biofuels and value-added compounds can be designed, allowing the recovery of multiple compounds with lower environmental impacts and a sustainable economic growth. Pigments are natural compounds used in high-end applications due to their colour and high biological interest that can be found in several marine resources. However, the conventional techniques to recover them require the use of complex and time-consuming methodologies that may lead to the degradation and/or loss of stability of the compounds, high energy consumption, and low yields of extraction. Alternative solvents such as aqueous solutions of surfactants and ionic liquids (ILs) appear as more sustainable options that can improve thermal and chemical stability of pigments, obtain higher extraction yields, while minimizing the environmental impacts of the process. In this work, two procedures were developed to recover different pigments using alternative solvents, to overcome the bottlenecks found in the conventional methodologies. In the first work, a solid-phase extraction technique was used to fragmentate chlorophylls from xanthophyll. Then, to elute chlorophylls from AmberLite™ HPR900 OH resin, aqueous solutions of ILs revealed to be efficient solvents to valorize simultaneously xanthophyll and chlorophylls while reusing the resin in several new cycles of purification. The second work focused on the extraction of bacterioruberin pigment from Haloferax mediterranei with aqueous solutions of surfactants, being the non-ionic class the one that showed higher extraction yields. Moreover, the purification of bacterioruberin was also addressed by inducing a simple precipitation with ethanol as anti-solvent to recover proteins as a second added-value compound. In both works easy to implement and environmentally friendly procedures using water-based solvents were successfully proposed, being the operational conditions optimized to reduce both economic and environmental impacts, and to reach higher yields.As diretrizes da Agenda 2030 para o Desenvolvimento Sustentável foram muito claras. Novas estratégias precisam de ser encontradas para garantir um futuro sustentável. Desta forma, os recursos marinhos surgem como matérias-primas naturais e renováveis para integrar uma estrutura de biorefinaria marinha e uma abordagem de economia circular. Através da conversão de biomassa, uma produção integrada de biocombustíveis e compostos de valor acrescentado pode ser projetada, permitindo a recuperação de vários compostos com impactos ambientais mínimos e um crescimento económico sustentável. Pigmentos são compostos naturais utilizados em aplicações de elevado padrão devido à sua cor e ao seu alto interesse biológico, podendo ser encontrados em diversos recursos marinhos. No entanto, as técnicas convencionais para recuperá-los requerem o uso de metodologias complexas e demoradas que podem levar à degradação e/ou perda de estabilidade dos compostos, alto consumo de energia e baixos rendimentos de extração. Solventes alternativos, como soluções aquosas de líquidos iónicos e surfactantes, aparecem como opções mais sustentáveis que podem melhorar a estabilidade térmica e química dos pigmentos, obter rendimentos de extração mais altos, enquanto minimizam os impactos ambientais do processo. Neste trabalho, foram desenvolvidos dois procedimentos para recuperar diferentes pigmentos utilizando solventes alternativos, a fim de superar as dificuldades encontradas nos métodos convencionais. No primeiro trabalho, uma técnica de extração em fase sólida foi usada para fracionar clorofilas e xantofilas. A seguir, para eluir as clorofilas da resina AmberLite™ HPR900 OH, as soluções aquosas de líquidos iónicos revelaram-se solventes eficientes para valorizar simultaneamente xantofilas e clorofilas, e reaproveitar a resina em vários novos ciclos de purificação. O segundo trabalho teve como foco a extração do pigmento bacterioruberina com soluções aquosas de surfactantes a partir da Haloferax mediterranei, sendo a classe dos não iónicos a que apresentou maiores rendimentos de extração. Além disso, a purificação da bacterioruberina também foi abordada através de uma simples precipitação induzida com etanol como anti-solvente para recuperar proteínas como um segundo composto de elevado valor comercial. Em ambos os trabalhos foram desenvolvidos com sucesso procedimentos de fácil implementação e ambientalmente sustentáveis recorrendo ao uso de solventes aquosos, sendo as condições operacionais otimizadas para reduzir os impactos económicos e ambientais, e permitir alcançar rendimentos mais elevados.
Mestrado em Engenharia Química
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Thayer, James Benjamin. "Downstream Variability of Fluvial Form, Process, and Character in a Small Deglaciated Watershed, Southern Ontario." Thesis, 2012. http://hdl.handle.net/1807/33568.
Full textAbstract:
Many deglaciated watersheds possess complex longitudinal profiles and spatially variable sediment sources derived from the last glaciation. Accordingly, downstream patterns in fluvial forms and characteristics of the channel and floodplain may diverge from conventional ‘graded’ watershed models where channel slope decreases downstream. Within a small, deglaciated watershed, five distinct fluvial forms were identified and it was found that the watershed is organized in a spatially variable, but generally inverted arrangement with stable, low-energy forms dominating the upper watershed and more dynamic, high-energy forms in the lower watershed. As a consequence of this inverted and variable downstream succession, and the spatially erratic organization of glacial sediment sources, downstream trends in channel and floodplain characteristics are poorly defined, and in many cases, deviate from expected trends. This is most true for sedimentological variables where multiple co-dominant controls exist, while morphological and hydrological variables better conform to
expected downstream trends.
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Peens, Gert Petrus. "Evaluation of upstream and downstream process parameters on electrostatic precipitator performance / Gert Petrus Peens." Thesis, 2013. http://hdl.handle.net/10394/11932.
Full textAbstract:
New emission legislation regarding air pollution control, as instructed by the Department of Environmental Affairs (DEA) to Eskom Generation Power Stations, implies a particulate emission limit of 100 mg/Nm3 for all existing power stations by 2015 and 50 mg/Nm3 for all new and existing power stations by the year 2020. Some of Eskom’s power stations which are equipped with Electrostatic Precipitators (ESP’s) were not designed for this stringent legislation. It is also experienced that ESP’s and coal quality in Eskom have deteriorated over time, resulting in the performance of the ESP’s not meeting the legislative requirements.
Eskom is in the process of introducing various ESP enhancement projects to improve performance and aligning the operating philosophy to comply with the more stringent particulate emission legislation.
An ESP efficiency test was conducted at Lethabo Power Station to determine the current state of the plant and performance. The results of the test were compared with the original design base specifications to determine the relevant deficiencies which contribute to high emissions and poor ESP performance.
It was aimed to develop an ESP simulation model and validate the outputs with the test data. This study endeavours to demonstrate the greater impact on ESP performance when the ESP is operated outside the design specification.
It is further aimed to demonstrate that a solution to the problem of high emissions is not only contributed by the variables within the ESP itself. This study is a coal to stack evaluation considering the ESP variables and the upstream conditions of the ESP that form part of the entire process. The intention of this study is to demonstrate the importance of operating an ESP at the designed parameters and highlight the significance of proper maintenance.
It was learned that before any ESP enhancement technology can be implemented, the ESP and upstream conditions must be in accordance with design specifications. The implementation of an ESP enhancement technology will have no merit or justification on a unit that is being operated outside of its design specifications.
The results obtained from the ESP simulation model correlated well with the ESP efficiency test data. The expectation of the model to assist operators and engineers to operate ESP’s according to the designer’s specifications was conceded.MIng (Mechanical Engineering), North-West University, Potchefstroom Campus, 2014
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Oliveira, Francisca Isabel Nunes. "Implementation and optimization of downstream strategies to manipulate Microcystis aeruginosa growth and toxicity." Master's thesis, 2018. http://hdl.handle.net/1822/74152.
Full textAbstract:
Dissertação de mestrado em Biologia Molecular, Biotecnologia e Bioempreendedorismo em PlantasMicrocystis aeruginosa is a microorganism that belongs to the group of cyanobacteria, which includes more than 2000 prokaryotic species. Despite being often called blue-green algae, cyanobacteria are classified as Gram negative bacteria. The microrganisms of this species possess an intracellular cyanotoxin– microcystin (MC) – that presents a great potential in therapeutic terms, both as an antimicrobial and as anticancer/antitumor agent. On the other hand, this toxin is dangerous to humans and animals, when present in high concentrations in water. These two factors, along with the high price of the cyanotoxin (above 28 000 €.mg-1), make the study of M. aeruginosa extremely interesting, specifically when it comes to its production and removal processes. In order to contribute to a decrease in the cost of MC production, this work studied the downstream processing of M. aeruginosa, particularly its harvesting process, which is responsible for 20 – 30 % of the total costs at industrial scale. The focus of this work was the optimization and comparison of the harvesting efficiency of M. aeruginosa using flocculation induced by pH and by different flocculant agents, namely: aluminium chloride (AlCl3), ferric chloride (FeCl3), and chitosan (Ch). The results obtained showed a harvesting efficiency (HE) above 90 % after 8 hours of treatment using pH 3 and 4 to induce flocculation of M. aeruginosa. Regarding the floculation induced by flocculant agents, it was possible to observe a HE of 92 % after just 4 hours using 3.75 mg.L-1 of FeCl3. Among the methods tested, this was the highest HE and was achieved at a ZP value of -8.98 mV. The optimization performed with ZP alteration allowed not only to reach higher HEs for all flocculation types, but also to decrease the used dosage of flocculant agents. Moreover, the optimal conditions of flocculation were found for a ZP in the range of -6.7 and -20.7 mV.
A Microcystis aeruginosa é um microrganismo pertencente ao grupo das cianobactérias, que inclui mais de 2000 espécies procariontes. As cianobactérias, apesar de serem comummente designadas de algas verde-azuladas, são classificadas como sendo bactérias gram-negativas. Os microorganismos deste espécie produzem uma cianotoxina, a microcistina (MC), que apresenta um enorme potencial terapêutico, quer como agente anticancerígeno/antitumoral e antimicrobiano. Por outro lado, esta toxina apresenta um elevado risco para os humanos e animais quando presente em elevadas concentrações na água. Estes dois fatores, juntamente com o elevado preço desta cianotoxina (mais de 28000 € por mg), tornam o estudo da M. aeruginosa de extremo interesse, especialmente no que toca ao seu processo de produção e recolha. Com a finalidade de contribuir para a diminuição do custo de produção da MC, este trabalho foi realizado de forma a estudar o processo de recolha da M. aeruginosa, que é frequentemente responsável por 20 a 30 % dos custos totais de produção à escala industrial. Deu-se um especial enfoque à otimização e comparação da eficiência de recolha da M. aeruginosa para processos de floculação induzida por uma gama de pH de 2 a 12 e pela utilização de diferentes concentrações de três agentes floculantes: o cloreto de alumínio (AlCl3) a 15, 7.5, 3.75 e 1.88 mg.L- 1, o cloreto de ferro (FeCl3) a 30, 7.5, 3.75 e 1.88 mg.L-1 e o quitosano (Ch) a 7.31, 2, 0.5 e 0.25 mg.L-1. Os resultados revelaram que as maiores eficiências de recolha na floculação induzida por pH, acima de 90 %, foram obtidas após 8 horas de tratamento usando pH 3 e 4. Relativamente à floculação promovida por agentes floculantes, através da modificação do potencial zeta foi possível obter uma eficiência de 92 % após 4h utilizando 3.75 mg.L-1 de FeCl3. De entre os métodos testados, esta foi a melhor eficiência de recolha alcançada, sendo obtida para um valor de potencial zeta de -8.98 mV. A optimização dos processos, levada a cabo pela alteração do potencial zeta, permitiu verificar que as melhores eficiências foram obtidas para um intervalo de potenciais zeta entre -6.7 e -20.7 mV, e possibilitou também a utilização de menores dosagens de agentes floculantes.
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Kao, Tzu-Chien, and 高子健. "The Effect of Work-in-process Mix on the Efficiency and the Integration of Upstream and Downstream Scheduling." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/78564183281220339409.
Full textAbstract:
碩士國立臺灣大學
工業工程學研究所
100
Machine capability matrix can be used to express the differences in capability between parallel machines. When the WIP arrival mix does not match the machine capability matrix, the workload of parallel machines cannot be balanced. Thus, the throughput of the shop composed of parallel machines is constrained. This research proposes WIP allocation method which can conjecture the optimal WIP allocation likelihood. However, there’s limit that the balanced workload cannot be reached. This method can help to derive the WIP mix preferred by the machine capability matrix. Belonging to different processes, shops have difference in machine capability matrix. The WIP arrival mix downstream shop faced with are what upstream shop scheduled to process. If the WIP mix that upstream shop scheduled does not match the machine capability matrix of downstream shop, the throughput is constrained by the schedule of upstream shop. Thus, the throughput in upstream shop is higher than that in downstream shop. This research points out the problem and proposes an integration method on upstream and downstream scheduling. It can help to find the way to improve the throughput of downstream shop. The downstream shop can select the improving policy to request the upstream shop to change the scheduled WIP mix. We performed an experiment by considering only the stochastic processes of WIP Arrivals. The results indicate that the throughput of upstream shop is higher than that in downstream shop before using the improving policy. It also shows that the throughput of upstream shop may be decreased slightly by using improving policy. However, the throughput of downstream shop may be increased significantly. Thus, this method can mitigate the imbalanced throughput between upstream and downstream shop.
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Hui, Chou Ming, and 周銘輝. "Effects of Scale Up and Downstream Process on Mycelium Biomass and Bioactive Ingredients by Cordyceps militaris Submerged Fermentation." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/37480368098490654079.
Full textAbstract:
碩士大葉大學
生物科技碩士在職學位學程
102
This study aims to investigate the effects of industrial fermentation production and the follow-up manufacturing processes on the bioactive ingredients and mycelial biomass production of the medicinal fungi, Cordyceps militaris DL-1. Using 50 L, 750 L, and 1,500 L fermentor to cultivate for different durations, various rotational speeds and media sterilization method, collocate with the subsequent procedures including condensation duration, temperature, and drying method to analyze the effects on mycelium biomass and the amount of bioactive ingredients including cordycepin, mannitol, adenosine and EPS. By 50 L fermentor, the mycelium biomass and cordyceps on the 7th day are the highest, mannitol and EPS got most on the 4th day and adenosine on the 5th day. 750 L fermentor with 35 rpm is conducive to mycelium biomass and EPS as 45 rpm is beneficial for cordycepin, mannitol and adenosine production. As carbon and nitrogen sources of the media were sterilized separately, the mycelial biomass, cordycepin and mannitol are 48.0%, 29.9%, and 5.8% higher respectively comparing to carbon and nitrogen sources sterilized together. In the subsequent procedures of condensation, heating, and drying, the mycelial biomass and bioactive ingredients demonstrated that the economic benefit of industrial production as fermented for 30 minutes at 80 ℃ and drying with lyophilizing technique. The results show that in the industrial fermentation procedure of Cordyceps militaris submerged fermentation, fermentation process scale up and the subsequent procedures may affect the production of bioactive ingredients. Carbon and nitrogen sources of the media sterilized separately benefits the production enhancement of mycelial biomass, cordycepin and mannitol.
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Matos, Manuel João de Almeida Albuquerque Brandão. "Process development and optimization towards the production of a non-antibody scaffold-based biotherapeutic." Master's thesis, 2015. http://hdl.handle.net/10362/50529.
Full textAbstract:
In a context of “green” biotechnology the tendency is to increase investment in methods that rely on microrganisms for the production of biological compounds. The use of these methodologies, contrary to those that rely on the use of chemical components, translate into a higher sustainability in the economical, social and environmental sectors.
The upstream development is deeply connected with the cultivation of microrganisms expressing all kind of recombinant proteins. Regarding this work, special attention was given to a specific type of recombinant protein, nanofitins. Nanofitins are artificial proteins created through the technique of ribosome display which consists in several cycles of selection with the goal of creating a synthetic protein with affinity to a specific target.
The objective in this experimental work was to implement a protocol for the production and purification of a nanofitin at a pilot scale. Regarding upstream analysis, different specific growth rates were tested during fed-batch administration on a 30L bioreactor, as well as operation times and small scale growth conditions were optimized. At upstream it was concluded that the use of a specific growth rate of 0,175h-1 during fed-batch is sufficient to maximize the microbial growth and its biomass production, as well as the use of only one resistance antibiotic, ampicillin, managed to optimize these parameters. At the downstream level different conditions were studied, namely the techniques of ion exchange chromatography and hydrophobic interaction. The technique of tangential flow filtration was also tested, showing that the use of this technique with two cutoffs, 30kDa and 5kDa, followed by a cationic exchange chromatography is the combination of techniques which presented higher productivities with higher purity ratio. To fulfill GMP requirements, the remotion of the content of endotoxins in the final product was also assessed. The use of Sartobind STIC nano successfully removed up to 97% of endotoxins content on the final product.Num contexto de biotecnologia “verde” a tendência em investir em métodos que incorporem microrganismos para produção de compostos biológicos é cada vez maior. O uso destas metodologias, ao contrário de metodologias com métodos químicos, traduzem-se numa maior sustentabilidade a nível económico, social e ambiental. O desenvolvimento do upstream está muito relacionado com o cultivo de microrganismos que expressam proteínas recombinantes. No âmbito deste trabalho foi estudado um tipo específico de proteínas recombinantes chamadas nanofitinas. As nanofitinas tratam-se de proteínas geradas pela técnica de ribosome display onde através de diversos ciclos de seleção consegue-se gerar proteínas sintéticas com afinidade para um target. O objetivo deste trabalho experimental foi de implementar um protocolo de produção e purificação de uma nanofitina à escala piloto. No que diz respeito ao upstream foram testadas diferentes taxas específicas de crescimento durante a administração do fed-batch num bioreactor de 30L, assim como otimização de tempos de operação e condições de cultura à pequena escala foram testados. Foi concluído que o uso de uma taxa específica de crescimento de 0,175h-1 durante o fed-batch permite maximizar o crescimento microbiano e biomassa produzida assim como o uso de apenas um antibiótico de resistência, ampicilina, otimiza estes mesmos parâmetros. No downstream foram estudadas condições que permitissem purificar com sucesso a nanofitina, nomeadamente as técnicas de cromatografia de permuta iónica e interação hidrofóbica. Foi também testada a técnica de filtração tangencial, onde foi concluído que a operação sequencial de dois cutoffs diferentes, 30kDa e 5kDa, seguido da técnica de cromatografia de permuta iónica é a metodologia que apresenta produtividades mais elevadas com maior grau de pureza. Visando atingir parâmetros GMP, foi ainda testada a remoção de endotoxinas do produto final. O uso de uma Sartobind STIC nano mostrou remover com sucesso 97% o conteúdo de endotoxinas no produto final.
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Cunha, Bárbara Martins Paiva da. "Development of integrated strategies for the downstream processing of human stem cells for clinical application." Doctoral thesis, 2016. http://hdl.handle.net/10362/20208.
Full textAbstract:
During the past decades, human stem cells (hSC) have emerged as a therapeutic
alternative for several diseases. However, their clinical transfer still faces major challenges. Amongst them are the production of high cell amounts, the delivery of those high cell numbers at low volumes with minimal presence of residuals, while assuring the desired phenotype and function/potency. Although substantial efforts have been placed on the large-scale production of hSC and/or derivatives, the development of scalable approaches for downstream processing (DSP) of hSC and the establishment of fully integrated platforms for cell manufacturing has been long awaited.
The goal of this PhD project was to establish scalable and integrated DSP strategies for the clarification, volume reduction (concentration) and washing unit operations for humanderived adult and pluripotent SC. Human mesenchymal stem cells (hMSC) and human induced pluripotent stem cells (hiPSC) were used as challenging and complex cell-based products. Combining membrane technology and chromatographic tools, a flexible platform based on cost-effective, robust, scalable, and compatible with current good manufacturing practices (cGMP) processes, compliant with different stem cell types and that can be transferred to clinical/industrial settings was developed.
Initially, it was evaluated the applicability of filtration methodologies, as dead end
filtration and tangential flow filtration, for the clarification and concentration of hMSC,
respectively. Different process parameters and their impact on hMSC quality were studied.
Polypropylene filters with pore sizes higher than 75 μm ensured the efficient removal of
microcarriers from the cell suspension bulk, without compromising cells’ recovery yields or viability. Furthermore, hMSC could be successfully concentrated up to a factor of 10 while maintaining their identity, differentiation capacity and high cell viability, allowing for the recovery of over 80% of viable cells; an initial cell concentration higher than 2 x 105 cell/mL, and polysulfone membranes with pore sizes higher than 0.45 μm were identified to be key conditions to obtain such concentration factors; shear rate and permeate flux were also shown to impact cells’ recovery yields, viability and quality.
The applicability of the previously developed TFF methodologies to hiPSC processing,
was assessed applying a Design of Experiments (DoE) approach. The impact of the process parameters of the volume reduction unit operation on hiPSC’s recovery, viability, expression of pluripotency markers and pluripotency differentiation potential was assessed and compared with results previously attained with hMSC. A mathematical model of the process was designed and after understanding how the shear rate, permeate flux and cell load factors interacted between them, the condition that maximized cell recovery and viability showed to be similar between both stem cell types. A robustness analysis was performed and the success rate of these operating conditions was assessed (65 - 70%). A parametric study was then conducted, identifying that increasing the shear rate (up to 3370 s-1) allowed to achieve the specified requirements for cell recovery yield (> 80%) and viability (> 90%) in 100% of the cases and no impact in hiPSC’s proliferation capacity, expression of pluripotency markers and differentiation potential was observed.(...)
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YANG, Meng-Shu, and 楊孟書. "A Study of Product Innovations, Process Innovations and Vertical Integration – The Model of Monopoly in the Upstream and Duopoly in the Downstream." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/65028432577545585231.
Full textAbstract:
碩士東海大學
國際貿易學系
98
This research attempts to establish an economic mathematics model based on the concept of vertical integration, assuming that there is monopoly competition in the upstream and duopoly competition in the downstream competition in the market, and discuss the influence of the R&D expenditures and profits to the process innovation（adopted by vertically integrated firm）and product innovation（adopted by non-integrated firm）. We extend the model of Buehler and Schmutzler（2008）、Milliou（2004）, and Yin and Zuscovitch（1998）. The previous two studies of each discusses respectively on the spillover effects and the intimidation effect under the vertical integration, whereas the third study discusses the issue of product innovation. The primarily difference of this article and the above-mentioned three studies lies in the fact that we assumed the vertically integrated firm adopts cost-reducing strategy and the non-integrated firm take the product innovation as its strategy. The results are as follows:（1）The equilibrium output of old products of the vertically integrated firm is larger than non-integrated firm.（2）The vertically integrated firm increases its cost-reducing investment and the non-integrated firm will increases the investment of product innovation, so the vertically integrated firm doesn’t have the intimidation effect instead have the racing effect.（3）When market size of new products expands, it is beneficial to the vertically integrated firm（profits increase）, and enables the firm to increase the R&D of the process innovation; whereas it is not necessarily conducive to the non-integrated firm（to old products, it is unfavorable）, and the firm will devote more effort to product innovation.（4）When market size of old products is shrinking, it is unfavorable to the vertically integrated firm（profits decrease）, and enables the firm to reduce the R&D of the process innovation; whereas it is not necessarily beneficial to the non-integrated firm（to old products, it is unfavorable）, and the firm will devote more effort to product innovation.
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D'Ascensão, João Diogo Mendes. "Study of kefiran production from cheese whey." Master's thesis, 2020. http://hdl.handle.net/10773/30416.
Full textAbstract:
Cheese whey is the main by-product of dairy industries, which is massively
produced worldwide. Its disposal may represent a serious environmental issue
due to its high organic content, therefore, it is of interest to find more solutions
for its valorisation. An interesting approach is the conversion of its lactose into
value-added products through microbial fermentation. Kefiran is an
exopolysaccharide with approximately equal amounts of D-glucose and Dgalactose, whose remarkable properties make it possible to be of use in a
wide range of applications in the medicine, pharmaceutical and food
industries. This polymer can be produced during fermentation, with the use of
kefir grains, a complex microbial community embedded within a kefiran matrix,
containing several species of lactic acid bacteria (LAB), acetic acid bacteria
(AAB) and yeasts, living in symbiose. Nevertheless, the bacterium
Lactobacillus kefiranofaciens is considered to be the main responsible for
kefiran production.
The objective of this work was the study of kefiran production, by kefir grains,
in cow’s cheese whey (CWC), diluted cow’s cheese whey (CWCD), sheep’s
cheese whey (CWS) and in synthetic medium (MRSL broth). In this study,
fermentations in batch and fed-batch mode were performed.
Initially, MRSL broth medium was used to optimise the process. A
fermentation time of 100 h was found to be optimal, since it led to the highest
kefiran productivity value. The ideal stirring speed was concluded to be 80
rpm, as it provided the best balance between kefiran production and kefir
grains’ conservation. Relatively to the optimal initial lactose concentration,
results were dependant on the stirring speed, with no noticeable inhibition by
substrate occurring. The best results in terms of kefiran concentration, 1.640
g/L, and productivity, 0.390 g/L.day, were both reached after 100 h of
fermentation, using a MRSL broth medium containing 40 g/L of lactose, at 160
rpm.
Regarding cheese whey, kefiran production values were promising. The
highest concentration of kefiran, 1.190 g/L, was attained in the fed-batch
fermentation of the cheese whey sample CWC, which lasted for 510 h, at 80
rpm, while the highest kefiran productivity value, 0.224 g/L.day, was achieved
in the batch fermentation of the cheese whey sample CWCD, after 50 h, at 80
rpm.
When characterising the kefiran samples produced with the different media,
an acid hydrolysis confirmed a glucose to galactose ratio of approximately 1:1
and, together with the analysis by Fourier-transform infrared (FTIR)
spectroscopy, also confirmed that kefiran was successfully produced in this
study. Additionally, the analysis by scanning electron microscopy (SEM)
revealed a foam-like structure with a high porosity level, which is a very
desirable characteristic for the production of kefiran scaffolds.
This study showed that it is possible to produce kefiran with the use of a lowcost carbon source, such as cheese whey, with fairly solid results, even
though the process scale-up still needs to be addressed to enable an eventual
industrial implementation.O soro de leite é o subproduto principal da indústria dos lacticínios, e é massivamente produzido a nível mundial. O seu descarte pode representar um sério problema ambiental devido à sua elevada carga orgânica, portanto, é de interesse procurar mais soluções para a sua valorização. Uma alternativa interessante é a conversão da sua lactose em produtos de valor acrescentado, através da fermentação microbiana. O kefirano é um exopolissacarídeo com aproximadamente as mesmas quantidades de Dglucose e D-galactose, cujas notáveis características tornam possível o seu uso numa ampla gama de aplicações na medicina e na indústria farmacêutica e alimentar. Este polímero pode ser produzido durante a fermentação com grãos de kefir, uma complexa comunidade microbiana embebida numa matriz de kefirano, contendo várias espécies de bactérias do ácido lático (LAB), bactérias do ácido acético (AAB) e leveduras, que vivem em simbiose. Contudo, a bactéria Lactobacillus kefiranofaciens é considerada como sendo a principal responsável pela produção de kefirano. O objetivo deste trabalho foi o estudo da produção de kefirano, utilizando grãos de kefir, em soro de leite de vaca (CWC), soro de leite de vaca diluído (CWCD), soro de leite de ovelha (CWS) e em meio sintético (MRSL broth). Neste estudo, foram realizadas fermentações em modo batch e fed-batch. Inicialmente, o meio MRSL foi utilizado para a otimização do processo. O tempo de fermentação de 100 h foi considerado como ótimo, porque resultou no valor de produtividade de kefirano mais elevado. A agitação ideal foi de 80 rpm, uma vez que demonstrou o melhor balanço entre a produção de kefirano e a conservação dos grãos de kefir. Relativamente à ótima concentração inicial de lactose, os resultados foram dependentes da agitação, onde não foi observada uma inibição por substrato significativa. Os melhores resultados em termos de concentração de kefirano, 1,640 g/L, e produtividade, 0,390 g/L.dia, foram ambos alcançados após 100 h de fermentação, usando um meio MRSL broth contendo 40 g/L de lactose, a 160 rpm. Em relação aos ensaios com soro de leite, os valores de produção de kefirano foram promissores. A concentração mais alta de kefirano, 1,190 g/L, foi atingida na fermentação em fed-batch da amostra de soro de leite CWC, que durou 510 h, a 80 rpm, enquanto que o valor mais alto de produtividade de kefirano, 0,224 g/L.dia, foi alcançado na fermentação em batch da amostra de soro de leite CWCD, depois de 50 h, a 80 rpm. Ao caracterizar as amostras de kefirano produzidas com os diferentes meios, uma hidrólise ácida confirmou o rácio de glucose para galactose de aproximadamente 1:1 e, juntamente com a análise por espectroscopia de infravermelhos com transformadas de Fourier (FTIR), também confirmou que o kefirano foi produzido com sucesso neste estudo. Adicionalmente, a análise por microscopia eletrónica de varrimento (SEM) revelou uma estrutura tipo espuma com um elevado nível de porosidade, o que constitui uma característica muito desejável para a produção de scaffolds de kefirano. Este estudo demonstrou que é possível produzir kefirano a partir de fontes de carbono de baixo custo, como o soro de leite, com resultados bastante sólidos, apesar de ainda ser necessário estudar o aumento de escala do processo, de modo a tornar possível uma eventual implementação industrial
Mestrado em Biotecnologia