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1
Glyn, Julian E. H. "Modelling of batch and fed-batch ethanol fermentation." Master's thesis, University of Cape Town, 1989. http://hdl.handle.net/11427/21832.
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Two series of batch and fed-batch fermentations were carried out using S.cerevisiae in a semi-defined medium containing 200 gl-1 glucose as limiting substrate. Growth rates were calculated and the data used to test the applicability of eight empirical kinetic models. The form proposed by Levenspiel, combining the concept of a limiting ethanol concentration with a power-law form, gave the best results with these data. Glucose concentration was found to have a far smaller, though not negligible, effect on growth rate under these conditions. It was also observed that in fed-batch fermentations the total substrate uptake rate of the broth became constant soon after commencement of feeding, without cessation of growth. It is suggested that ethanol inhibits the synthesis of a rate-controlling enzyme in the glycolyti·c chain, but no previous work could be found to support or refute this explanation. A quasi-mechanistic model of growth under the condition of constant substrate consumption rate is formulated and discussed.
2
Jewaratnam, Jegalakshimi. "Batch-to-batch iterative learning control of a fed-batch fermentation process." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/1901.
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Recently, iterative learning control (ILC) has been used in the run-to-run control of batch processes to directly update the control trajectory. The basic idea of ILC is to update the control trajectory for a new batch run using the information from previous batch runs so that the output trajectory converges asymptotically to the desired reference trajectory. The control policy updating is calculated using linearised models around the nominal reference process input and output trajectories. The linearised models are typically identified using multiple linear regression (MLR), partial least squares (PLS) regression, or principal component regression (PCR). ILC has been shown to be a promising method to address model-plant mismatches and unknown disturbances. This work presents several improvements of batch to batch ILC strategy with applications to a simulated fed-batch fermentation process. In order to enhance the reliability of ILC, model prediction confidence is incorporated in the ILC optimization objective function. As a result of the incorporation, wide model prediction confidence bounds are penalized in order to avoid unreliable control policy updating. This method has been proven to be very effective for selected model prediction confidence bounds penalty factors. In the attempt to further improve the performance of ILC, averaged reference trajectories and sliding window techniques were introduced. To reduce the influence of measurement noise, control policy is updated on the average input and output trajectories of the past a few batches instead of just the immediate previous batch. The linearised models are re-identified using a sliding window of past batches in that the earliest batch is removed with the newest batch added to the model identification data set. The effects of various parameters were investigated for MLR, PCR and PLS method. The technique significantly improves the control performance. In model based ILC the weighting matrices, Q and R, in the objective function have a significant impact on the control performance. Therefore, in the quest to exploit the potential of objective function, adaptive weighting parameters were attempted to study the performance of batch to batch ILC with updated models. Significant improvements in the stability of the performance for all the three methods were noticed. All the three techniques suggested have established improvements either in stability, reliability and/or convergence speed. To further investigate the versatility of ILC, the above mentioned techniques were combined and the results are discussed in this thesis.
3
Bridger, Lee. "Improved control of fed-batch fermenters." Thesis, University of Exeter, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.288001.
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Vanichsriratana, Wirat. "Optimal control of fed-batch fermentation processes." Thesis, University of Westminster, 1996. https://westminsterresearch.westminster.ac.uk/item/94908/optimal-control-of-fed-batch-fermentation-processes.
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Optimisation of a fed-batch fermentation process typically uses the calculus of variations or Pontryagin's maximum principle to determine an optimal feed rate profile. This often results in a singular control problem and an open loop control structure. The singular feed rate is the optimal feed rate during the singular control period and is used to control the substrate concentration in the fermenter at an optimal level. This approach is supported by biological knowledge that biochemical reaction rates are controlled by the environmental conditions in the fermenter; in this case, the substrate concentration. Since an accurate neural net-based on-line estimation of the substrate concentration has recently become available and is currently employed in industry, we are therefore able to propose a method which makes use of this estimation. The proposed method divides the optimisation problem into two parts. First, an optimal substrate concentration profile which governs the biochemical reactions in the fermentation process is determined. Then a controller is designed to track the obtained optimal profile. Since the proposed method determines the optimal substrate concentration profile, the singular control problem is therefore avoided because the substrate concentration appears nonlinearly in the system equations. Also, the process is then operated in closed loop control of the substrate concentration. The proposed method is then called "closed loop optimal control". The proposed closed loop optimal control method is then compared with the open loop optimal feed rate profile method. The comparison simulations from both primary and secondary metabolite production processes show that both methods give similar performance in a case of perfect model while the closed loop optimal control provides better performance than the open loop method in a case of plant/model mismatch. The better performance of the closed loop optimal control is due to an ability to compensate for the modelling errors using feedback.
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Rivera, David. "Growth kinetics of Bacillus thuringiensis batch, fed-batch and continuous bioreactor cultures." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0011/NQ40287.pdf.
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Arndt, Michael. "Eine schnelle Glucoseanalytik zur Regelung biotechnischer Prozesse." [S.l. : s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=971240787.
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Minihane, B. J. "Micro-computer control of fed-batch pullulanase biosynthesis." Thesis, Cranfield University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.280848.
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Lindell, Per Ingemar. "Dynamic operation of mammalian cell fed-batch bioreactors." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/16509.
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Hussenet, Clément. "Instrumentation, modélisation et automatisation de fermenteurs levuriers à destination oenologique." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLC009/document.
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Le vin est un milieu peu propice à la croissance de la levure mais il est néanmoins possible de la faire croître sur base de vin enrichit en nutriments et dilué pour diminuer la concentration en éthanol. En vue de l’élaboration des vins effervescents par une seconde fermentation, produire la levure Saccharomyces cerevisiae dans ces conditions est indispensable pour l’acclimater mais il s’agit d’un enjeu complexe qui doit prendre en compte de nombreux paramètres physico-chimiques mais aussi économiques. En effet, les paramètres opératoires peuvent induire des conditions de croissance pouvant affecter le développement de la levure. Seule la levure S. cerevisiae (Fizz+) a été utilisée car elle est spécialement sélectionnée pour cette seconde fermentation en vase clos. Le principal enjeu était donc d’obtenir une bonne adaptation de la levure à croître dans un milieu hydro-alcoolique, conditions contraignantes pour elle, mais aussi d’obtenir une production maximale.Nous avons tout d’abord étudié en fioles Erlenmeyer (250 mL) l’influence de divers paramètres : conditions physico-chimiques, concentrations en nutriments, concentration minimale en levure sèche active nécessaire à une bonne activité ainsi que son temps de réhydratation.Dans un deuxième temps, nous avons effectué des propagations en mode batch dans un bioréacteur (5 L) pour valider les conclusions réalisées à la suite de l’étude en Erlenmeyer et ainsi étudier l’influence de différentes aérations sur la production de S. cerevisiae. Les données obtenues ont servi de base pour comparer les améliorations apportées par le procédé développé en mode fed-batch. Les concentrations en levures obtenues suite à l’optimisation des conditions du milieu de culture en cinq litres sont supérieures d’un facteur cinq à celles obtenues dans la pratique en cave.Ensuite l’étude s’est concentrée sur le développement d’un nouveau procédé d’alimentation en nutriments pour cultiver S. cerevisiae en métabolisme respiratoire dans des cuves réalisées par la société partenaire du projet, OEno Concept. La nouveauté réside dans la façon de réguler la température de la culture qui se fait simultanément à l’apport des nutriments suite au dégagement de chaleur lors de la croissance de S. cerevisiae. Un brevet a été déposé sur cette technologie. Ce nouveau procédé a permis une augmentation de la productivité cellulaire, d’un facteur supérieur à quatre, car il a permis aux levures de s’adapter à cet environnement stressant et a favorisé l’oxydation du glucose au détriment de la fermentation<br>Wine is an aggressive/stressful growth medium; it is depleted of micronutrients, rich in ethanol and very poor in assimilable nitrogen. Despite all these difficulties, it is possible to grow yeast in a medium largely based on wine by diluting the ethanol concentration and enriching the medium with micronutrients, a carbon source and assimilable nitrogen. It is, desirable to propagate Saccharomyces cerevisiae in such environment in order to produce a culture of yeast adapted to a second fermentation of alcoholic beverages. Production of microorganism in wine growing environment, is a complex issue that must take into account many, physicochemical and economic parameters. Indeed, the operating parameters can affect the development of yeast in a bioreactor. Therefore, it is important to know the most influential parameters on growth. The strain S. cerevisiae (Fizz+), a commercial strain that has been selected for the second fermentation in bottles, was used during this project. The propagation process served to increase the amount of yeast as well as to adapt the yeast to grow in an alcoholic environment. We first studied in shake-flasks cultures various physicochemical conditions such as nutrients concentration, the rehydration time and the minimum concentration of active dry yeast necessary for good yeast activity.In a second step, we performed batch fermentations in bioreactors (5 L) to confirm the conclusions from the shake-flask cultures and additionally to study the influence of aeration on S. cerevisiae production. The data obtained served as a basis for performing fed-batch cultures. The yeast concentrations obtained as a result of the optimization of the conditions of the culture medium in five liters were five times greater than those obtained in actual industrial production processes. The next step was to develop an automated fed-batch culture to grow S. cerevisiae respiratively in partnership with the industrial partner of the project, OEno Concept. The novelty of the process is the way in which the growth medium feed-rate is linked to the heat produced by the growing S. cerevisiae.This research has allowed an increase in cell productivity, by a factor greater than four, thanks to the novel process in stressful growth environment promoting respiration with regard to fermentation
10
Longster, Joanne. "Transcriptome analysis of CHO cells throughout fed-batch culture." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/13808/.
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11
Chan, Man Ting. "Optimizing food waste composting process in fed-batch composter." HKBU Institutional Repository, 2015. https://repository.hkbu.edu.hk/etd_oa/217.
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Composting is considered as an effective and sustainable food waste treatment technology from the perspectives of volume reduction, stabilization and releasing the pressure on landfills. Community composter is a decentralized composting facility in fed-batch operational mode which is usually being installed in the backyard of institutes, hospitals, housing estate etc. to handle the food wastes generated daily. Albeit numerous operational issues including high initial acidity and oil content, poor decomposition and odor generation are commonly encountered in these facilities, which make it difficult to be accepted by the public. Therefore, the aim of the present study is to develop a composting mix formulation that can provide a solution to all these issues in a fed-batch food waste composting process. The first phase of this study aims at finding out an optimized formulation in a batch-scale food waste composting process through the use of alkaline amendments and microbial inoculum. For the first two experiments, artificial food wastes were prepared by mixing 1.3kg bread, 1kg boiled rice, 1kg cabbage, 0.5kg fully boiled pork and mixed with sawdust to obtain a C/N of 30 and adjusted moisture of the mixtures to 55%. The effect of different concentrations of zeolite compared to lime was studied in the first experiment. Zeolite was amended with food wastes and sawdust mixtures at 2% (ZI-2), 5% (ZI-5), 10% (ZI-10) to compare with lime in 2.25% (L-2.25) w/w (dry weight basis) and composted for 56 days. Results demonstrated that 10% of zeolite was optimal amendment rate compared to lower dosage of zeolite (2% & 5%) with stronger pH buffering capacity and greater decomposition efficiency. Addition of 2.25% of lime buffered the pH efficiently but increased the ammonia loss significantly which eventually reduced total nitrogen (TN) content of final product and posed odor emission problem. Amendment of 10% zeolite provided a higher adsorption affinity on ammonia resulting in 2.05% of TN value of final product which was higher than 1.72% of lime treatment. Furthermore, significantly higher seed germination 150% was achieved of ZI-10 compost compared to 135% of L-2.25 due to low ammonium content of product. The first experiment showed that application of less than 10% zeolite was not sufficient to buffer the acidity; as a result, organic matter decomposition was inhibited. However, the cost and reduction in treatment percentage of food waste in 10% application rate of zeolite is an issue of concern. To tackle this dilemma, food waste was amended with struvite salts at 1:2 molar ratio of MgO and K2HPO4 (Mg:P) with or without zeolite amended at either 5% or 10% amendment (Mg:P, Z5 + Mg:P & Z10 + Mg:P) and a control treatment with food waste only was also included. Results showed that treatment of Z10 + Mg:P was synergistically achieved of pH and EC buffering, and N conservation but not for the case of 5 % zeolite. Treatment of Z10 + Mg:P further reduced the N loss to 18% compared to 25% and 27% of Mg:P and Z5 + Mg:P respectively. However, there was insignificant difference in the final nitrogen content and decomposition rate among all treatments with struvite salts amendment. Comparing to the treatment of Z-10 of the first experiment to Z10 + Mg:P of the second experiment, Z-10 showed superior performance since better decomposition efficiency, shorter time to require to pass the GI (28 Days) and lower cost because of salts exclusion. To develop a multipurpose formulation for the fed-batch operational food waste composter, high lipids problem in food waste cannot be neglected because it is a critical factor to hinder the decomposition efficiency. Inoculation of oil degradative microorganisms was reported as an effective approach to facilitate the lipids. Therefore, the third experiment was to investigate the overall composting performance supplemented with 10% zeolite and microbial consortium. 10% zeolite with bacterial consortium significantly reduced the lipid contents from 7% to 1% compared to control treatments. Furthermore, treatments amended with 10% zeolite was proved to reduce ammonia emission and total volatile fatty acids level in the composting mass, therefore the total odor emission level can be reduced. Zeolite at 10% was found to be a suitable optimum additive for both synthetic and real-food wastes. Therefore, treatment of 10% zeolite with bacterial consortium is selected as an optimized formulation for further study of its application in a fed-batch composter. Following the food waste zeolite composting formulation obtained in Phase I, the aim of Phase II was to develop an ideal composting mix formulation for on-site commercial composters. Although the results have been demonstrated 10% zeolite with bacterial consortium facilitated the composting efficiency in batch composter, those amendments may be over-estimated if applied in a fed batch composter by using real food wastes. With this constraint, the applicability of these additives in commercial fed-batch composter needs to be assessed using locally generated food wastes. Treatments included food waste and sawdust mixtures at 4:1 mixing ratio (wet weight basis) were mixed with 2.25% of lime (L2.25), 10% of zeolite (Z10) and 10% zeolite with bacterial inoculum (Z10+O) and a control of food waste with sawdust mixture only was also included. 35 kg compost mixture was fed into each composter respectively daily for a period of 42 days. Only Z10+O was the most suitable composting mix for fed-batch food waste composting process with continuous sustained high temperature (55-60oC), optimal moisture (55%-60%), alkaline pH and low EC during the experimental period. Bacterial inoculum significantly improved the lipids decomposition from 22.16% (C) to 3.10% (Z10+O) after the composting period. In contrast, lime and zeolite alone treatments could not maintain the optimal pH that led to reduce degradation and longer stabilization period. Only compost taken from Z10+O treatment could be classified as mature compost. The aim of the third study phase was to examine an optimal application rate of food waste compost produced from decentralized food waste composter for plant. A plant growth experiment was conducted in this phase to evaluate the change in soil properties and plant growth of Brassica chinensis and Lycopersicon esculentum. The experiment was conducted in a loamy soil amended with 0%, 2.5%, 5% and 10% food waste compost amendment rate compared to the control soil with chemical fertilizer amendment only. Results indicated that 5% was the optimal application rate of food waste compost for both crops among all treatments which can be evidenced by the highest biomass production and nutrients value of the plant tissues. Plant available nutrients such as NH4+, NO3-, PO43- were proportionally increased with increase in compost application rate. However, 2.5% of the food waste compost did not provide sufficient nutrients for plant growth and 10% showed negative effects due to increased salts content. Plants amended with chemical fertilizer had relatively low biomass production compared to compost amended treatments due to soil compaction and fast leaching of nutrients. It can be concluded that application of 10% zeolite with microbial consortium is an ideal composting mix formulation for on-site commercial composters and 5% is an optimal application rate of food waste compost of Brassica chinensis and Lycopersicon esculentum
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Hadley, Trevor Deon. "The application of fuzzy control to fed-batch fermentation." Master's thesis, University of Cape Town, 1995. http://hdl.handle.net/11427/21700.
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Bibliography: pages 101-105.<br>Fermentation processes are highly nonlinear and subject to variability. The fermentation's states are not readily available on-line and therefore the application of closed loop control schemes have been hindered. It was decided to investigate fuzzy control as it is able to deal with systems whose operation does not easily fit into the mathematical framework of traditional control approaches such as fermentations where the systems are highly nonlinear. The fermentation of lysine is an emergent industry in South Africa and it was therefore decided to focus on this fermentation. The control of penicillin fermentation was also investigated as it closely resembles the fermentation of lysine. A review of the types of control and estimation techniques used in the literature for biosystems was done to assess state of art in biocontrol. This covered optimal control techniques, neural networks, fuzzy controllers and adaptive control techniques. The operation and properties of fuzzy controllers were investigated. A specific form of fuzzy controller, presented in the literature, which was shown to correspond to a PI controller with a nonlinear gain was discussed. The effect of the number of output sampling points was analysed and it was found that the number of output sampling points used has an effect on the output and input response. It was also found that a higher number of sampling points results in a nonlinear integral constant and a non linear gain which has more resolution. The fuzzy controller's output response equations were found to be of a PI form with a possible bias term irrespective of the number of sampling points. The fuzzy controller was shown to yield better output and input response to that of an equivalently tuned linear PI controller for a first, second and third order system because it is able to take advantage of its nonlinear form. It was also shown that it is possible to obtain less severe input action for relatively the same value of SSE (sum of squared errors) when a higher number of sampling points is used for a first order system with dead time.
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Abadli, Merouane. "Robust control of fed-batch cultures of Escherichia coli." Electronic Thesis or Diss., université Paris-Saclay, 2021. http://www.theses.fr/2021UPASG072.
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Escherichia coli est un hôte cellulaire très répandu pour la production industrielle de produits bio-pharmaceutiques à base de protéines. Cette production, principalement opérée en mode fed-batch, vise à maximiser la productivité de la biomasse. Cependant, l'accumulation d'acétate durant la culture inhibe la capacité respiratoire des cellules et diminue leur performance métabolique. Dans cette thèse, des stratégies de commande de l'alimentation sont envisagées pour éviter l'accumulation d'acétate et maximiser la productivité de la biomasse. A cette fin, des schémas de commande et d'estimation à base de modèle sont développés pour réguler le taux de croissance de la biomasse et la concentration en acétate. Les méthodes de commande vont du contrôle par modèle générique au contrôle prédictif par modèle non linéaire, et les variables non mesurées sont estimées à l'aide du filtre de Kalman "sans parfum". Les développements ont porté sur la robustesse des méthodes proposées en raison de la nature incertaine du bioprocédé. La performance et la robustesse des schémas de commande et d'estimation sont testées et ajustées au travers de différents scénarios de simulation. Des cultures en mode Fed-batch de la souche E. coli BL21(DE3) sont réalisées avec succès sur un bioréacteur de laboratoire, mettant en évidence le potentiel des stratégies proposées dans un contexte de conditions opératoires en temps réel. Les stratégies de commande proposées dans cette thèse permettent un gain moyen jusqu'à 20% de la productivité de la biomasse par rapport au mode de fonctionnement conventionnel<br>Escherichia coli is a widespread cellular host for the industrial production of protein-based biopharmaceuticals. This production, mainly operated in fed-batch mode, aims to maximize biomass productivity. However, the accumulation of acetate during the culture inhibits the cells respiratory capacity and lowers their metabolic performance. In this thesis, closed-loop feeding control strategies are considered to avoid acetate accumulation and maximize biomass productivity. To this end, modelbased control and estimation schemes are developed to regulate the biomass growth rate and the acetate concentration. The control methods ranged from the Generic Model Control and Nonlinear Model Predictive Control, and the non-measured variables are estimated using the Unscented Kalman Filter. The developments focused on the robustness of the proposed methods due to the uncertain nature of the bioprocess. The performance and robustness of the control and estimation strategies are tested and tuned by means of different scenarios of simulation runs. Fed-batch cultures of E. coli BL21(DE3) strain are successfully carried on a lab-scale bioreactor, highlighting the potential of the proposed strategies in real-time conditions. The proposed control strategies presented in this thesis lead to an average gain of up to 20% in biomass productivity compared to the conventional operating mode
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Lam, Ming-Chi. "In silico dynamic optimisation studies for batch/fed-batch mammalian cell suspension cultures producing biopharmaceuticals." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/45465.
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Mammalian cell cultures are valuable for synthesis of therapeutic proteins and antibodies. They are commonly cultivated in bioindustry in form of large-scale suspension fed-batch cultures. The structure and regulatory responses of mammalian cells are complex, making it challenging to model them for practical process optimisation. The adjustable degrees of freedom in the cell cultures can be continuous variables as well as binary-type variables. The binary-type variables may be irreversible in cases such as cell-cycle arrest. The main aim of this study was to develop a general model for mammalian cell cultures using extracellular variables and capturing major changes in cellular responses between batch and fed-batch cultures. The model development started with a simple model for a hybridoma cell culture using first-principle equations. The growth kinetics was only linked to glucose and glutamine and the cell population was divided into three cell-cycle phases to study the phenomenon of cell-cycle arrest. But there were certain deficiencies in predicting growth rates in the death phase in fed-batch cultures although it was successful to simultaneously optimise a combination of continuous and binary-irreversible degrees of freedom. Thus, the growth kinetics was further related to amino acids concentration and cellular responses to high versus low concentration of glutamine and glucose based on a Chinese hamster ovary cell-line where amino acids data were available. The model contained 192 parameters with 26 measured cell culture variables. Most of the sensitive parameters were able to be identified using the Sobol' method of Global Sensitivity Analysis. The model could capture the main trends of key variables and be used to search for the optimal working range of the controllable variables. But uncertainties in the sensitive model parameters caused non-negligible variations in the model-based optimisation results. It is recommended to couple such off-line optimisation with on-line measurements of a few major variables to tackle the real-time uncertain nature of the complex cell culture system.
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Montgomery, Paul Anthony. "On-line optimisation of a multivariable fed-batch fermentation process." Thesis, Liverpool John Moores University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252788.
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Montague, G. A. "Inferential self-tuning control of the fed-batch penicillin fermentation." Thesis, University of Newcastle Upon Tyne, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278876.
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Pham, Thi Bich Hop. "Modelling and control of microbial fed-batch and pH-auxostat processes." Doctoral thesis, Stockholm : Tekniska högsk, 1999. http://www.lib.kth.se/abs99/pham0212.html.
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Chen, Haisong. "Methods and algorithms for optimal control of fed-batch fermentation processes." Thesis, Cape Peninsula University of Technology, 2005. http://hdl.handle.net/20.500.11838/1151.
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Thesis (MTech (Electrical Engineering))--Cape Peninsula University of Technology, 2005<br>Fennentation is the process that results in the fonnation ofalcohol or organic acids on
the basis of growth of bacteria, moulds or fungi on different nutritional media (Ahmed
et al., 1982). Fennentation process have three modes of operation i.e. batch, fed-batch
and continuous ones. The process that interests a lot of control engineers is the
fed-batch fennentation process (Johnson, 1989). The Fed-batch process for the
production ofyeast is considered in the study.
The fennentation is based on the Saccharomyces cerevisiae yeast. It grows in both
aerobic and anaerobic environmental conditions with maximum product in the aerobic
conditions, also at high concentration of glucose (Njodzi, 200I). Complexity of
fed-batch fennentation process, non-linearity, time varying characteristics, application
of conventional analogue controllers provides poor control due to problems in tuning
individual loops and the process characteristics. The problem for control of the
fed-batch process for the production of yeast is further complicated by the lack of
on-line sensors, lack ofadequate models as a result ofpoorly understood dynamics. The
lack of on-line sensors results in the impossibility oftuning the analogue controllers in
real time.
The process for propagation of yeast in aerobic conditions is considered in the
dissertation. The experiments are conducted at the University of Cape Town (DCT),
Department of Chemical Engineering with a bioreactor and bio-controller combined in
a Biostat ® C lab scale plant (H. Braun Biotech International, 1996).
The bio-controller has built in Pill controller loops for control variables, with the
ability to adjust the controller parameters i.e. P, D and I through the serial interface
(SeidIer, 1996).
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Picó, Marco Enrique. "Nonlinear robust control of biotechnological processes. Application to fed-batch bioreactors." Doctoral thesis, Universitat Politècnica de València, 2008. http://hdl.handle.net/10251/2901.
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La tesis está centrada en los biorreactores en "fed-batch", dada la importancia de estos reactores agitados de alta densidad para la producción industrial eficiente de proteinas, encimas,.... utilizando microorganismos modificados genéticamente. El problema real está caracterizado por la escasez de medidas en línea. Otros problemas importantes son la (fuerte) incertidumbre paramétrica y la presencia significativa de no linealidades. Además de los problemas comentados, en el caso de biorreactores en ``fed-batch'' es necesario tratar con equilibrios parciales, es decir, sólo respecto a una parte de las variables. Los objetivos principales de la tesis son:
- La búsqueda de un conjunto limitado de estructuras de modelos representando la mayor parte de los casos de interés industrial.
- La solución, como primer paso en una aproximación de ``abajo-arriba'', del problema de control para el caso de cultivos puros con un sólo substrato limitante y asumiendo el oxígeno está en exceso.
- El diseño de controladores para regular la tasa específica de crecimiento de los microorganismos. Utilizando solamente medidas en línea de biomasa y volumen, sin ninguna estimación de la tasa de crecimiento ni de ninguna otra variable. Y, finalmente, teniendo en cuenta las no linealidades del sistema, la incertidumbre y otros fenómenos.
- Tratar el problema citado anteriormente de estabilidad parcial.
El último punto ha marcado la elección de las posibles técnicas a estudiar para resolver el problema de control. En concreto:
- Técnicas de control geométrico(Fradkov et al.). El problema de control de biorreactores puede ser visto como uno de "control de coordinación". La solución está relacionada con algunas propiedades específicas de los
sistemas como la invarianza y la atractividad local de conjuntos no triviales en el espacio de estados.
- Flatness. Aunque comunmente asociada con la linealización exacta, un sistema puede ser plano dentro de un subconjunto del espacio de estados sin ......<br>Picó Marco, E. (2004). Nonlinear robust control of biotechnological processes. Application to fed-batch bioreactors [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/2901<br>Palancia
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Han, Ling. "Physiology of Escherichia coli in batch and fed-batch cultures with special emphasis on amino acid and glucose metabolism." Doctoral thesis, KTH, Biotechnology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3334.
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<p>The objective of this work is to better understand themetabolism and physiology of<i>Escherichiacoli</i>(W3110) in defined medium cultures with thelong-term goal of improving cell yield and recombinant proteinproductivity.</p><p>The order of amino acid utilization in<i>E. coli</i>batch cultures was investigated in a medium with16 amino acids and glucose. Ser, Pro, Asp, Gly, Thr, Glu andAla were rapidly consumed and depleted at the end of theexponential phase, while His, Arg, Val, Met, Ile, Leu, Phe, Lysand Tyr were consumed slowly during the following linear growthphase. The uptake order correlated to the maximum specificconsumption rate. Of the rapidly consumed amino acids onlyglyine and threonine improved growth when added individually.Serine was the first amino acid to be consumed, but inhibitedglucose uptake initially, which presumably is related to thefunction of PTS. Valine inhibited cell growth could be releasedby isoleucine. The critical medium concentration of valinetoxicity was 1.5 - 3 µmol L<sup>-1</sup>. Valine uptake was associated with exchange ofisoleucine out of the cells.</p><p>Glycine significantly increased the cell yield,<i>Y</i><sub>x/s,</sub>and growth rate of<i>E. coli</i>in batch cultures in a glucose-mineral medium.Maximum effect occurred at pH 6.8, at 6 - 12 mmol L<sup>-1</sup>glycine, and below 1.15 g dw L<sup>-1</sup>.<sup>13</sup>C NMR technique was employed to identify [1-<sup>13</sup>C], [2-<sup>13</sup>C]and [1,2-<sup>13</sup>C]acetate in the cultures supplied with [2-<sup>13</sup>C]glycine. The NMR data revealed that littledegradation of added glycine occurred, and that serine/glycinebiosynthesis was repressed below 1.15 g dw L<sup>-1</sup>, implicating that glycine was a source ofglycine, serine, one-carbon units, and threonine. Above 1.15 gdw L<sup>-1</sup>, 53% of the consumed glycine carbon was excretedas acetate. Degradation of glycine was associated with anincreased uptake rate, cleavage by GCV, and degradation of bothglycine- and glucose-derived serine to pyruvate. This switch inmetabolism appears to be regulated by quorum sensing.</p><p>A cell density-dependent metabolic switch occurred also inthe central metabolism. A 2 - 3 fold decrease in mostglycolytic and TCA cycle metabolites, but an increase inacetyl-CoA, occurred after the switch. The acetate productionrate decreased throughout the culture with a temporary increaseat the switch point, but the intracellular acetate poolremained relatively constant.</p><p>Two mixtures of amino acids were fed together with glucosein fed-batch cultures of<i>E. coli</i>W3110 pRIT44T2, expressing the recombinantprotein ZZT2. One mixture contained 20 amino acids and theother 5 so-called 'protein amino acids': Ala, Arg, Met, His andPhe. Although the amino aids increased the cell yield anddecreased the proteolysis rate in both cases, ZZT2 productionwas decreased. A decrease of ZZT2 synthesis rate is consideredto be the reason. Further studies of the 5 amino acidsindicated that a few amino acids disturb metabolism.</p><p>Carbon mass balances were calculated in glucose limitedfed-batch cultures of<i>E. coli</i>. In the end, the carbon recovery was ~90% basedon biomass, CO<sub>2</sub>and acetate, but ~100% if the all carbon in themedium was included. Outer membrane (OM) constituents,lipopolysaccharide, phospholipids, and carbohydratescontributed to 63% of the extracellular carbon. Little celllysis occurred and the unidentified (~30%) carbon was assumedto constitute complex carbohydrates. A novel cultivationtechnique Temperature-Limited Fed-Batch (TLFB) is developed toprevent OM shedding in high-cell density cultures.</p><p><b>Keywords</b>: Escherichia coli, amino acids, glycine, quorumsensing, metabolic switch, metabolite pools, carbon balance,outer membrane, lipopolysaccharide, batch culture, fed-batchculture</p>
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Warth, Benedikt. "Design and Application of Software Sensors in Batch and Fed-batch Cultivations during Recombinant Protein Expression in Escherichia coli." Thesis, Linköping University, The Department of Physics, Chemistry and Biology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-12530.
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<p>Software sensors are a potent tool to improve biotechnological real time process monitoring and control. In the current project, algorithms for six partly novel, software sensors were established and tested in a microbial reactor system. Eight batch and two fed-batch runs were carried out with a recombinant <em>Escherichia coli</em> to investigate the suitability of the different software sensor models in diverse cultivation stages. Special respect was given to effects on the sensors after recombinant protein expression was initiated by addition of an inducer molecule. It was an objective to figure out influences of excessive recombinant protein expression on the software sensor signals.</p><p>Two of the developed algorithms calculated the biomass on-line and estimated furthermore, the specific growth rate by integration of the biomass changes with the time. The principle of the first was the application of a near infrared probe to obtain on-line readings of the optical density. The other algorithm was founded on the titration of ammonia as only available nitrogen source. The other two sensors analyzed for the specific consumption of glucose and the specific production of acetate and are predicted on an in-line HPLC system.</p><p>The results showed that all software sensors worked as expected and are rather powerful to estimate important state parameters in real time. In some stages, restrictions may occur due to different limitation affects in the models or the physiology of the culture. However, the results were very convincing and suggested the development of further and more advanced software sensor models in the future.</p>
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Svensson, Marie. "The temperature-limited fed-batch technique for control of Escherichia coli cultures." Doctoral thesis, Stockholm : School of Biotechnology, Royal Institute of Technology, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4154.
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Büdenbender, Christine [Verfasser]. "Modellentwicklung und Trajektorienplanung für Fed-Batch Fermentationen mit komplexen Nährmedien / Christine Büdenbender." Aachen : Shaker, 2005. http://d-nb.info/1181619815/34.
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Khatri, N. K. (Narendar Kumar). "Optimisation of recombinant protein production in Pichia pastoris:single-chain antibody fragment model protein." Doctoral thesis, Oulun yliopisto, 2011. http://urn.fi/urn:isbn:9789514295850.
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Abstract Potential lethal diarrhoea caused by enterotoxigenic Escherichia coli strains is one of the most common diseases in young pigs. It can be cured by single-chain antibody fragments (scFv), which can be produced in recombinant microorganisms. Pichia pastoris, a methylotrophic yeast, is generally considered an interesting production system candidate, as it can secrete properly folded proteins. These proteins accumulate in high concentrations during fermentation, reducing the cost for product recovery. Strong inducible AOX1 promoter, widely used in P. pastoris for fast, inexpensive production, is typically induced by methanol. The high oxygen demand of methanol metabolism makes oxygen supply a major parameter in cultivations requiring special process design strategies. In standard fed-batch cultivation, dissolved oxygen concentration inside a bioreactor is kept at a certain level by pumping air and pure oxygen into the reactor. There are safety concerns over the handling of oxygen, especially at a large scale. Therefore, there is a need to develop a production process under oxygen-limited conditions. This dissertation studies the development of a cost-efficient production process of scFv in P. pastoris. Both methanol and oxygen parameters influence the production process and the objective was to find a robust production process. Fed-batch cultivations were performed in a 10 L scale bioreactor. The effects of lower oxygen level, methanol concentration, glycerol feeding duration and specific substrate-uptake rates on product formation were studied. A P. pastoris GS115 his4 strain under an AOX1 promoter system expressing scFv was used in this study. The fed-batch fermentations were carried out in a bioreactor with basal salt media. In this doctoral dissertation, a process was developed for a single-chain antibody fragment (scFv) production in P. pastoris. The product levels of 3.5 g L-1 scFv in culture supernatant were achieved and a production process was designed without additional need of pure oxygen, thus relieving safety requirements and lowering the amount of methanol. The process developed during this research may potentially be utilised by both academia and industry having interests in expressing proteins in P. pastoris. The methanol-uptake control strategy is beneficial for those products that suffer from degradation or modification during limited feeding of methanol<br>Tiivistelmä Enterotoksigeenisten E.coli kantojen aiheuttama ripuli on porsaiden tavallisimpia tauteja, joka voi johtaa jopa kuolemaan. Tautia voidaan hoitaa yhdistelmä-DNA-tekniikalla tuotetuilla vasta-ainefragmenteilla (scFv). Metylotrofista Pichia pastoris hiivaa pidetään kiinnostavana vasta-ainefragmenttien tuottoisäntänä, koska se pystyy erittämään oikealla tavalla laskostuneita proteiineja. Näitä proteiineja kertyy fermentointiprosessissa solujen ulkopuolelle korkeina pitoisuuksina, mikä vähentää tuotteiden talteenottokustannuksia. Vahva metanolilla indusoituva AOX1-promoottori on laajassa käytössä P. pastoris tuottosysteemissä tuoton nopeuden ja alhaisten kustannusten ansiosta. Metanolin aineenvaihdunta vaatii paljon happea, joten riittävän tehokas hapen liuottaminen on tärkeimpiä fermentointiparametreja ja vaatii erityisiä prosessin toteutusstrategioita. Perinteisessä fed-batch-fermentoinnissa liuenneen hapen pitoisuus bioreaktorissa pidetään halutulla tasolla lisäämällä ilmaa ja puhdasta happea reaktoriin. Koska hapen käsittelyyn liittyy turvallisuusriskejä erityisesti teollisuusmittakaavassa, happirajoitteisissa olosuhteissa toimiva tuotantoprosessi olisi hyödyllinen. Tässä väitöstutkimuksessa kehitettiin kustannustehokasta prosessia scFv-:n tuottoon P. pastoris hiivalla. Metanoliin ja happeen liittyvät parametrit ovat olennaisia prosessiin vaikuttavia tekijöitä. Tavoite oli kehittää yksinkertainen ja käytännöllinen prosessi. Työssä tutkittiin alhaisen happitason, metanolin pitoisuuden, glyserolisyötön keston ja substraattien spesifisten kulutusnopeuksien vaikutuksia tuotteen muodostumiseen 10 litran bioreaktorissa. Isäntäkantana oli P. pastoris GS115 his4, jossa scFv-ekspressiota säädeltiin AOX1 promoottorilla. Fed-batch fermentointien kasvatusalustana käytettiin Basal Salt Medium alustaa (BSM). Väitöstyössä kehitettiin tavoitteiden mukainen vasta-ainefragmenttien tuottoprosessi P.pastoris hiivalle. Menetelmällä saavutettiin tuotepitoisuus 3,5 g L-1 kasvatusliemen supernatantissa ilman puhtaan hapen lisäystarvetta, ja siten metanolin kulutus väheni ja prosessiturvallisuus parani verrattuna perinteisiin prosesseihin. Kehitetty prosessi soveltuu käytettäväksi sekä akateemisessa tutkimuksessa että teollisuudessa tuotettaessa erilaisia proteiineja P. pastoris hiivalla. Metanolin kulutuksen säätöstrategia on erityisen hyödyllinen tuotteille, joilla ongelmana on proteolyysi tai muokkautuminen metanolirajoitteisessa fermentoinnissa
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Masse, Daniel I. "Psychrophilic anaerobic digestion of swine manure slurry in intermittently fed sequencing batch reactor." Thesis, University of Ottawa (Canada), 1995. http://hdl.handle.net/10393/9611.
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Animal manure management practices, principally in regions where there is a surplus of manure are often detrimental to the environment and also represent a potential hazard to human and animal health. The primary objective of this study was to evaluate the feasibility of psychrophilic anaerobic digestion (PAD) in sequencing batch reactors (SBR) as a low cost and easy to operate process to: (a) reduce the pollution potential of swine manure slurry; (b) recover energy; and (c) reduce odours of swine manure slurry. Experiments were carried out in 12 40-Litre SBRs operated under different conditions. Experimental results indicated that PAD of swine manure slurry at 20$\sp\circ$C in intermittently fed SBR: (1) reduced the pollution potential of swine manure slurry by removing 85 to 95% of the soluble chemical oxygen demand (SCOD); (2) produced biogas at rates from 0.48 to 0.66 L of CH$\sb4$ per gram of volatile solids (VS) fed; and (3) successfully reduced odours. In all experimental runs, the PAD of swine manure slurry in SBR was found very stable. Other interesting findings were that PAD in SBR process does not require mixing and can be intermittently fed only once and three times a week without affecting the SBR stability and performance. The second objective of this study was to model PAD of swine manure slurry in SBR in order to: (1) increase knowledge of PAD in SBR; and (2) predict process performance. Existing mathematical models of anaerobic digestion formed the basis for the two models proposed in this study for PAD in SBR. These two models were: (1) a simple model that considered only two populations of bacteria as well as particulate solubilization rate; and (2) an advanced model that considered six populations of bacteria as well as the interaction between the biological, liquid (physico-chemical) and gas phases. The simple model predicted reasonably well the trend in VA, SCOD accumulation as well as methane production. The advanced model which made use of a large number of kinetic constants also predicted reasonably well the methane production as well as the trend in accumulation in acetic, propionic and butyric acids, dissolved and gaseous hydrogen and SCOD.
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Micael, Karlberg. "Soft sensor application on lactate controlled fed-batch cultivation for monoclonal antibody production." Thesis, Linköpings universitet, Teknisk biologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-117179.
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Monoclonal antibody producing cells are of great interest and used frequently in the field of biomedical research, diagnostics and therapy with increasing need for better systems to more efficiently produce antibodies at a lower costs. In this project three fed-batch cultivations of hybridoma cells (HB-8696) were cultured in a stirred tank reactor with the use of a soft sensor to monitor the lactate concentration and as well as a dielectric probe for biomass measurements. In addition, a protocol for growing the inoculum was also successfully produced and a previous batch cultivation was also analyzed which gave crucial information about stoichiometrically relation in the feed medium which was used in the fed-batch cultivations. The BioSenz Analyzer was used for on-line lactate concentration monitoring and was later used to control the feed profile to avoid overflow metabolism in two of the three fed-batch cultivations. However, nothing conclusive could be said about the lactate controller as of yet which needs further research.
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Xie, Liangzhi. "Stoichiometric medium design and nutritional control in fed-batch cultivation of animal cells." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/10287.
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Lynch, Hilary. "A study of cyclic fed batch culture for the production of secondary metabolites." Thesis, University of Surrey, 1995. http://epubs.surrey.ac.uk/844465/.
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The broad aim of this research was to evaluate a cyclic fed batch culture system for the production of secondary metabolites and to identify a physiological parameter that correlated with product induction for optimisation of the process. A cyclic fed batch culture (CFBC) system was successfully established using a constant flow of glucose limited medium into the bioreactor, and culture stability was found to be dependent on time of flow initiation. A 40% increase in product concentration was obtained using CFBC when compared to batch culture with the organism Saccharopolyspora erythraea. CFBC induced secondary metabolite production with the organism Amycolatopsis orientalis, despite the lack of production in batch culture. Product concentration was dependant on the growth rate range used in CFBC for both organisms, although the trends of productivity differed for the two. Product stability at quasi steady-state during CFBC depended on the variation in biomass concentration obtained. A number of physiological parameters were measured in both batch culture and CFBC for correlation with product induction. A decrease in protein synthesis rate was observed to precede the induction of antibiotic in CFBC with both organisms, however, this trend was not observed in batch culture with Amycolatopsis orientalis. Although complex trends were observed for levels of RNA, total protein and the ratio of the two, no correlation with induction was observed. Profiled feeding regimes were employed for the manipulation of protein synthesis rates to optimise conditions for production. Increased productivity was not obtained, although protein synthesis rate was manipulated to reduce the timing of product induction at the start of the cycle. Morphological examination of the filamentous organism Saccharopolyspora erythraea, grown in either CFBC, chemostat culture or variable volume-chemostat culture, was found to indicate the organisms' physiological state. Productivity was highest in CFBC, coinciding with a transition from exponential to linear morphological growth and decreasing growth rate through the progress of one cycle. Where the morphological growth rate remained constant, that is in variable volume chemostat, productivity was lowest. In chemostat culture a morphological distribution was observed with both exponential and linear growth resulting in a product concentration higher than found in variable volume chemostat but less that in CFBC. Future work should include molecular studies to determine events leading to secondary metabolite induction. In conjunction with these studies development and unstructured model of the physiology is required. Clarification of the role of protein synthesis rates and particular components of the mechanism are required before this parameter can be discarded.
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Zizhou, Njodzi. "Studies on the fed-batch propagation of brewer's yeast in high gravity wort." Master's thesis, University of Cape Town, 2001. http://hdl.handle.net/11427/9751.
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Includes bibliographical references.<br>The traditional batch brewing process is characterised by serial yeast propagation to build sufficient yeast for pitching. This results in cyclic variations in yeast environment, leading to a slow brewing process. In high gravity brewing the carbohydrate utilisation is inefficient as a result of the Crabtree effect that occurs in the presence of high sugar concentration. When optimising the brewing process the characteristics of conventional batch brewing should be maintained. Fed-batch propagation of yeast is used to improve carbohydrate utilisation and the yeast biomass formation by controlling nutrient supply.
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Pareek, Tirusha. "Fed-batch bio-process development and optimization of cetuximab production at lab scale." Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-444795.
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Seer, Qiu Han. "Complex Dynamics in Fed-Batch Systems: Modeling, Analysis and Control of Alcoholic Fermentations." Thesis, Curtin University, 2017. http://hdl.handle.net/20.500.11937/56546.
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Modeling and control of fed-batch fermentation processes has been a subject of great interest to realize high productivity and yields from the fermentation technique. The goal of this dissertation was to gain insights into how the complex dynamic behaviors exhibited in fed-batch fermentation systems affect the stability of standard single-loop as well as non-standard feedback control structures. Novel PID stability theorems were established to help construct the controller stabilizing regions.
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Argyropoulos, Dimitris. "Stability of plasmid pPFF1 in recombinant Bacillus subtilis cultures and the effect of batch, chemostat and cyclic fed batch fermentation systems." Thesis, University of Reading, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265716.
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Lin, Hongying. "Cellular responses to the induction of recombinant genes in Escherichia coli fed batch cultures." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=960895345.
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Soyaslan, Elif Sukran. "Effect Of Ph On Erythropoietin Production By Recombinant Pichia Pastoris In Fed-batch Operation." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12612356/index.pdf.
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In this study, the effects of pH on therapeutically important protein, recombinant human erythropoietin (rhuEPO), production by Pichia pastoris was investigated at pH=4.0, 4.5, 5.0, 5.5 and 6.0. rHuEPO production was started by methanol induction in fed-batch mode. The highest cell concentration was obtained at pH=4.5 as 81.4 g L-1. The co-substrate substrate sorbitol, which was added batch-wise, was consumed at t=15 h of the operations at pH=4.0, 4.5 and 5.0. However as the pH increases above pH=5.0 the sorbitol consumption rate decreases. The highest rHuEPO concentration was achieved at pH=4.5 as 0.158 g L-1 which was 1.43-, 1.24-, 1.95- and 1.23-fold higher than those obtained at pH=4.0, 5.0, 5.5, and 6.0, respectively. Also at pH=4.5 overall cell yield on substrate was 0.51 g g-1 and overall rHuEPO yield on substrate was 1.45 mg g-1.
rHuEPO concentration was decreased in the last 3-6 hour of the operation due to proteolysis. Therefore extracellular protease concentrations in the medium were determined. As expected, since the investigated pH range was acidic, the amount of acidic proteases was found to be higher than neutral and basic proteases. Furthermore the total protease concentration increased linearly in the fermentation broth, having close values at different pH values. Thus, pH did not have a significant effect on extracellular protease activity.
Alcohol oxidase (AOX) activities showed similar behavior at different pH. The highest specific AOX activity was attained at pH=4.5, at which the highest rHuEPO concentration was achieved, as 110.1 U g-1 CDW.
Keywords:
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Ghaffari, Navid. "Effect of amino acid limitation and supplementation in Chinese hamster ovary fed-batch cultures." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/52061.
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Fed-batch processes are the industrial norm for the production of recombinant proteins such as monoclonal antibodies (MAb) from Chinese hamster ovary (CHO) cells. Optimization of such processes is an important objective of industry process development groups. Amino acid availability is a key factor that is controlled to achieve the desired product yield and quality. In order to improve fed-batch productivity, the individual effects of limiting the three depleted amino acids were investigated for three antibody expressing CHO cell lines. Specifically, the effects of limiting glutamine, asparagine and cysteine on the cell growth, metabolism, antibody productivity and quality were investigated. Cysteine limitation was found to be detrimental to both the cell proliferation and the productivity for all three CHO cell lines. In contrast, asparagine limitation had no significant effect on either their growth or productivity. Glutamine limitation resulted in a reduction in growth but not in cell specific productivity, again for all three cell lines. Neither glutamine nor asparagine limitation significantly affected the MAb glycosylation. However, the fucosylation ratio was reduced in the absence of cysteine. It was confirmed that cysteine is a rate limiting factor for the productivity and growth of the three CHO cell lines. Replenishing cysteine after 1 day of the limitation allowed the cells to regain their growth and productivity; however, this was not observed after 2 days of cysteine limitation. Under cysteine limitation there was increased oxidative damage to the mitochondria, possibly caused by reduced synthesis of co-enzyme A which is essential for functionality of the TCA cycle. Finally, a fed-batch protocol was developed to improve the MAb productivity of CHO-DXB11 cells and the results were compared to the results with a commercial feed. Although use of the commercial feed resulted in higher maximum cell and final MAb concentrations, maintaining the levels of cysteine yielded cell specific production rates that were comparable to the commercial feed culture. Overall, the results of this study showed that amino acid limitations have varied effects on the performance of CHO cell cultures, such that it is important to focus process development efforts on the critical amino acids.<br>Applied Science, Faculty of<br>Chemical and Biological Engineering, Department of<br>Graduate
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Brik, Ternbach Michael Alexander. "Modeling based process development of fed-batch bioprocesses : L-Valine production by Corynebacterium glutamicum." kostenfrei, 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=977739376.
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Jardon, Mario Alberto. "Modulating autophagy and glutamine metabolism in CHO cells to increase fed-batch process performance." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/42467.
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Valuable recombinant therapeutic proteins are routinely produced from Chinese hamster ovary (CHO) cells in fed-batch cultivations. An improved understanding of the physiological factors that affect cell proliferation, survival, productivity and product quality in fed-batch could contribute to facilitate general access to these products. This work describes the investigation of autophagy and glutamine metabolism in CHO cells for the purpose of increasing fed-batch process performance. The close link between glutamine deprivation and autophagy was found to greatly affect process performance, with an increase of the cellular lysosomal compartment correlated with decreased cell-specific productivity. The increased autophagic activity upon glutamine withdrawal was confirmed by the formation of GFP-LC3 fluorescent puncta and by an LC3 autophagic flux assay. The use of 3-methyl adenine (3-MA) to inhibit autophagy increased the yield of recombinant tissue plasminogen activator (t-PA) by 2.8-fold, without compromising the glycosylation capacity of the cells given that the t-PA fucosylation, galactosylation and sialylation all increased. A more comprehensive study of glutamine metabolism and autophagy performed, including by investigating 2 additional CHO cell lines expressing different antibody proteins. The mitochondrial and lysosomal changes in response to glutamine deprivation varied substantially between cell lines, illustrating how the susceptibility to autophagy can be cell-line dependent. Integrating the combined effect of enhanced proliferation (achieved through modulation of glutamine metabolism) and inhibition of autophagy (by treatment with 3-MA), a maximum 4.6-fold increase of t-PA production was obtained in fed-batch culture. Finally, autophagy and glutamine metabolism were explored in cancer cell lines, and produced original findings on the potential for Raman spectroscopy to analyze live cell physiological responses to conditions that trigger autophagy. Overall, this study illustrates the potential for a fruitful interaction between basic scientific research and applied biotechnology. The investigation of response mechanisms to cellular stress provided opportunities to both improve industrial processing and open new perspectives for basic biological research.
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Chuen-Im, Sasivimol. "Dynamic growth response and plasmid stability in cyclic fed-batch culture of Bacillus subtilis." Thesis, University of Reading, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298748.
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Kiss, Robert D. (Robert David). "Metabolic activity control of the L-lysine fermentation by restrained growth fed-batch strategies." Thesis, Massachusetts Institute of Technology, 1992. http://hdl.handle.net/1721.1/13225.
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Pimentel, Guilherme Araujo. "Controle robusto por realimentação linearizante parcial de bioreatores em modo de operação "FED-BATCH"." Pontifícia Universidade Católica do Rio Grande do Sul, 2010. http://hdl.handle.net/10923/3149.
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Previous issue date: 2010<br>This dissertation aims to use a general model to describe the growth of both bacteria Escherichia Coli as yeast Saccharomyces Cerevisiae in a bioreactor on fed-batch mode. In general, to maximize the production of biomass (microorganisms) by controlling the substrate (food) injected into the bioreactor. By the principle of bottle-neck, the maximum yield is obtained when the substrate level is maintained at a certain critical value which depends on biological variables of the process (which vary in time) and certain parameters with high degree of uncertainty. An alternative approach is the control of the by-product (acetate in the case of E. Coli or ethanol in the case of S. Cervisiae ) which should be maintained at levels close to zero and thus entire substrate is used in the production of biomass. Through the nonlinear model of the dynamic growth of the microorganism, it is proposed in this dissertation a robust control law based on the idea partial feedback linearization, in order to avoid measure a large number of biological variables di cult instrumentation. To improve the dynamic performance of the system, is also proposed a mechanism for online estimation and parametric adaptation of the reaction rate of glucose oxidation. Using the description of nonlinearities with the quasi-LPV approach and the formulation of stability conditions through linear matrix inequalities (LMIs), is designed a free linear dynamic, yield of feedback linearization, to ensure the robust stability (related to nonlinearities not canceled and parametric variations)in closed loop and also a certain performance. To verify the behavior of the proposed methodology are conducted several tests on simulations using the platform Matlab=Simulinkr, where is possible to study the behavior of the proposed strategy with regard to jobs available in the literature.<br>Esta dissertação apresenta um modelo geral que descreve a dinâmica do crescimento tanto da bactéria Escherichia Coli quanto da levedura Saccharomyces Cerevisiae quando produzidas em bioreatores operando no modo descontínuo com alimentação controlada (fed-batch). Em geral, procura-se maximizar a produção da biomassa (microorganismos) através do controle do substrato (alimento) injetado ao bioreator. Pelo princípio do bottle-neck, a máxima produtividade é obtida quando o nível de substrato é mantido em um determinado valor crítico que depende de variáveis biológicas do processo (que variam ao longo do tempo) e de certos parâmetros com elevado grau de incerteza. Uma alternativa a esta abordagem é através do controle do produto secundário (acetato no caso da E. Coli ou etanol no caso da S. Cervisiae) o qual deve ser mantido em níveis próximos a zero e desta forma todo o substrato é utilizado na produção de biomassa. A partir do modelo não linear da dinâmica de crescimento do microorganismo, propõe-se nesta dissertação uma lei de controle robusta baseada na ideia de realimentação linearizante parcial com o objetivo de evitar a medição de um elevado número de variáveis biológicas de difícil instrumentação. Para melhorar o desempenho dinâmico do sistema, também é proposto um mecanismo de adaptação paramétrica para a estimação online da taxa de reação da oxidação da glicose. Utilizando a descrição das não linearidades através da abordagem quasi-LPV e a formulação das condições de estabilidade por desigualdades matriciais lineares (LMIs), projeta-se a dinâmica linear livre, resultante da realimentação linearizante, de maneira a garantir a estabilidade robusta (em relação a não linearidades não canceladas e variações paramétricas) em malha fechada e também um certo desempenho. Para verificar o comportamento da metodologia proposta são realizados vários testes em simulações utilizando a plataforma Matlab=Simulinkr, onde estuda-se o comportamento da estratégia proposta em relação a trabalhos disponíveis na literatura especializada.
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Mkondweni, Ncedo S. "Modelling and optimal control of fed-batch fermentation process for the production of yeast." Thesis, Peninsula Technikon, 2002. http://hdl.handle.net/20.500.11838/1122.
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Thesis (MTech (Electrical Engineering))--Peninsula Technikon, Cape Town, 2002<br>Fermentation is the process that results in the formation of alcohol or organic acids on
the basis of growth of bacteria, moulds or fungi on different nutritional media (Ahmed
et al., 1982). Fermentation process have three modes of operation i.e. batch, fed-batch
and continuous mode ofoperation. The process that interests a lot of control engineers
is the fed-batch fe=entation process (Johnson, 1989). The Fed-batch process for the
production ofyeast is considered in the study.
The considered yeast in the study is the Saccharomyces cerevisiae. It grows in both
aerobic and anaerobic environmental conditions with maximum product in the aerobic
conditions, also at high concentration of glucose (Njodzi, 2001). Complexity of fedbatch
fe=entation process, non-linearity, time varying characteristics, application of
conventional analogue controllers provides poor control due to problems in tuning
individual loops and the process characteristics. The problem for control of the fedbatch
process for the production of yeast is further complicated by the lack of on-line
sensors, lack of adequate models as a result of poorly understood dynamics. The lack
of on-line sensors results in the impossibility of tuning the analogue controllers in real
time. The process for propagation of yeast in aerobic conditions is considered in the
dissertation. The experiments are conducted at the University of Cape Town (VCT),
Department of Chemical Engineering with a bioreactor and bio-controller are
combined in a Biostat ® C lab scale plant (B. Braun Biotech International, 1996).
The bio-controller has built in PID controller loops for control variables, with the
ability to adjust the controller parameters i.e. P, D and I through the serial interface
(Seidler, 1996).
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Bhardwaj, Vinayak. "Design of an optimised fed-batch process for insulin precursor production in Pichia pastoris." Master's thesis, University of Cape Town, 2011. http://hdl.handle.net/11427/10120.
Full textAbstract:
Includes bibliographical references (leaves 98-103).<br>The increasing prevalence of diabetes worldwide has greatly increased the demand for insulin, a key type of treatment for many diabetics. For this purpose, the methylotrophic yeast Pichia pastoris has emerged as an additional microbial host for recombinant insulin production. A genetically modified Pichia pastoris MutS strain, engineered to produce the insulin precursor, was used as the experimental system in this study in order to optimise the insulin production process. The experimental system developed in this study employed a two-stage fed-batch feeding strategy in which growth was optimised by feeding glycerol to boost biomass followed by induction of the gene encoding insulin precursor by feeding methanol.
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Johnston, Wayne. "Development of acetate threshold tracking control algorithms for Fed-Batch control of recombinant E.coli." Thesis, Johnston, Wayne (2002) Development of acetate threshold tracking control algorithms for Fed-Batch control of recombinant E.coli. PhD thesis, Murdoch University, 2002. https://researchrepository.murdoch.edu.au/id/eprint/41118/.
Full textAbstract:
In this thesis, algorithms for fed-batch control of recombinant E.coli were developed to avoid acetate formation while maximising biomass and total productivity. In general, previous algorithms have addressed the former goal only. Acetate threshold tracking nutrient controllers were developed, which provide the maximum nutrient feed rate without overflow metabolism to detrimental acetic acid production. These were particularly designed for performance in complex media. The primary problem in the development of such controllers is the non-availability of on-line sensors which can directly detect the acetate threshold. Two approaches were undertaken to provide acetate threshold detection and control using standard sensors.
The first approach used a gam scheduled Proportional-Integral-Derivative (PID) algorithm, formulated to compensate for process non-linearity via a gain schedule based on biomass estimation. The sensor availability problem was overcome by using standard measured variables to provide an on-line signal (inverse ofrespiratory quotient, l/RQ) proportional to the difference between the actual growth rate and the threshold growth rate. This allowed control of 1/RQ in a transition zone that represented growth rates just below the acetate threshold (0.2h-1). Growth to 38 g dcw/l without acetate accumulation was achieved. However, the relationship between 1/RQ and the growth rate threshold, demonstrated at low biomass concentrations of 10 - 15 g dew/I via controlled threshold traverse, changed over the course of cultivation to 38 g dew/I. This caused a significant degradation in controller threshold tracking. Additionally, the relationship between 1/RQ and growth rate was demonstrated only in a complex media system (i.e. complex base plus glucose feed supplemented with complex media components), limiting the controller's industrial applicability.
The second control approach used culture probing, in which new controlled variables related to the acetate threshold, based on the dissolved oxygen tension (DO), were generated from disturbances in the glucose feed rate. Although preliminary work used a starvation based DO-transient controller (using feed cessations), subsequent work focussed on a feed-up DO-transient controller (using feed pulses). To minimise m the detrimental effects of operation above the acetate threshold, the feed-up DO-transient control algorithm was formulated and tuned conservatively to minimise unnecessary threshold penetration while tracking. This proved particularly critical in complex media, which does not tend to balance acetate accumulation just above the threshold with acetate depletion just below. Using the conservatively tuned feed-up DO-transient controller, it was possible to track the acetate threshold over a range of 10 to 30 g dew/I in non-induced fermentation runs. Thereafter, using a glucose feed highly supplemented in complex media components (yeast extract, tryptone) to provide some culture anabolic requirement, threshold tracking to high cell density (58 g dew/I) was achieved. However, acetate accumulation was high(> lOOmM).
High cell density operation was found not to increase total productivity in a case study of the production of a viral coat protein (Jembrana disease virus sub-unit, JDV SU), in which the feed-up DO-transient controller underwent induction at 20 g dcw/l and 60 g dcw/l respectively. Total productivity was decreased from 0.27 g/l.h to 0.12 g/1.h, despite final biomass levels of 32 g dcw/l and 67 g dcw/1 respectively. This was due to reduced induction success in the high cell density run, caused by acetate accumulation. However, medium cell density induction of the feed-up DO-transient controller allowed superior total productivity to the commonly used high-limit pH-stat nutrient controller (0.27 g/l.h versus 0.24 g/l.h), due to decreased process time by the former.
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Engström, Patsy Maria. "Medium optimization of an E.coli fed-batch culture for the production of a recombinant protein." Thesis, KTH, Skolan för bioteknologi (BIO), 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-150696.
Full text
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Larsson, Johan. "High-throughput Fed-batch Production of Affibody® molecules in a novel Multi-fermentor system." Thesis, Linköping University, The Department of Physics, Chemistry and Biology, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-3490.
Full textAbstract:
<p>The present Master thesis describes the development and optimization of a fed-batch process for production of recombinant proteins in Escherichia coli BL21(DE3) in a multi-fermentor system. The system consists of six 1-liter fermentors, capable of producing 500-1500 μg/mL with present protocol.</p><p>Response surface methodology (RSM) was used for multivariable optimization regarding cultivation time, pH, temperature and feed rate. Optimal protein expression conditions were found out to be 17.8 h cultivation time, 36.7 ºC, pH 6.8 and a feed rate corresponding to specific growth of 0.23 h-1, on glucose substrate. The aggregation of expressed proteins to inclusion bodies, could not be affected by the various growth conditions employed during cultivations.</p><p>A study was conducted regarding growth conditions effect on phosphogluconoylation of expressed proteins. In ten fed-batch cultivations on glucose, LC/MS analysis showed a gluconoylated fraction with additional 178 Da mass, but no correlation between growth conditions and gluconoylation could be found. In two fed-batch cultivations on glycerol-feed, a lower feed rate resulted in no gluconoylation, while a higher did. An explanation would be that the lower amount of available intra-cellular carbon limits formation of gluconoylation precursors.</p>
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Chen, Ran [Verfasser]. "Fed-batch cultivations for high-yield production of tissue engineering related bio-molecules / Ran Chen." Hannover : Technische Informationsbibliothek und Universitätsbibliothek Hannover (TIB), 2011. http://d-nb.info/1014254612/34.
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Mukumba, Patrick. "Modelling of the performance of a batch biogas digester fed with selected types of substrates." Thesis, University of Fort Hare, 2013. http://hdl.handle.net/10353/d1016197.
Full textAbstract:
The increasing population and the rapid economic growth in South Africa have led to higher consumption of food resulting in the generation of large amounts of waste. In addition, South Africa has plenty of biomass from cattle, donkeys, horses, goats, pigs, chicken and sheep. However, anaerobic digestion could be an alternative solution for the utilization of these kinds of waste due to its environmental and economic benefits. Therefore, the main focus of the research was design, construct a field batch biogas digester, monitor its performance when fed with co-substrates and model the methane yield for an optimized mixing ratio.
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Huang, Shih-Wei, and 黃世偉. "Production of Extracellular Polysaccharide from Yeasts by Batch Fed-batch Fermentation." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/73620054875789240173.
Full textAbstract:
碩士<br>大同大學<br>生物工程研究所<br>90<br>Recently, being able to serve as a raw material for the synthesis of sulfated oligosaccharide, a potential anticoagulant, anti-virus and anti-tumor agent, yeast extracellular polysaccharide was becoming attractive. Batch and fed-batch fermentation was carried out in a 5-liter jar fermenter for the production of extracellular polysaccharide from Pichia holstii CCRC 22637. The fermentation medium consisted of the following ingredients per liter: glucose, 60; tryptone, 1; corn steep liquor, 1; KH2PO4, 10; MgSO4Ÿ7H2O, 0.2; MnSO4ŸH2O, 0.01; FeSO4Ÿ7H2O, 0.01 and NaCl, 0.01. Fermentation was carried out under the following conditions: initial working volume, 2 L; agitation, 450 rpm; aeration, 2 L min－1; temperature, 25°C and pH controlled at 4.7-5.3. After a 80-hr batch fermentation, 10.9 g L－1 dry weight of cells and 53.4 g L－1 dry weight of extracellular polysaccharide were obtained. When glucose and phosphate content in the medium was doubled, 10.6 g L－1 dry weight of cells and 73.2 g L－1 dry weight of extracellular polysaccharide was achieved at hr 124. In fed-batch fermentation, when half of initial glucose in the medium was exhausted, one tenth working volume of a solution containing 60 % (w/v) glucose and 5% (w/v) KH2PO4 was fed into fermenter and three repeated operations for such feeding were carried out throughout the fermentation process. After a 336-hr fed-batch fermentation, 12.3 g L－1 dry weight of cells and 112 g L－1 dry weight of extracellular polysaccharide were obtained. In a similar process of fed-batch fermentation, when nitrogen source was doubled in concentration, 21.6 g L－1 dry weight of cells and 129 g L－1 dry weight of extracellular polysaccharide were achieved at hr 364.
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Fan, Chiung-yi, and 范瓊藝. "Production of Nattokinase by Fed-batch Fermentation." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/34394843622088510882.
Full textAbstract:
碩士<br>大同大學<br>生物工程學系(所)<br>94<br>Abstract
We isolate a strain A from natto purchased from the local market. It was employed for the production of nattokinase by shaking culture at 180 rpm and 37 �aC. The optimum medium for the shaking culture was (g/l) : 3% soybean flour, 3% glucose, 0.5% CaCO3, 0.5% KH2PO4, 0.1% MgSO4．7 H2O. The nattokinase activity of 27 unit/ml was achieved after 48 h shaking culture.
The batch fermentation was performed using the same medium as the shaking culture at 300 rpm, 1 vvm of aeration, 37 �aC. 81.3 unit/ml of nattokinase activity was achieved after 42 h cultivation.
Fed-batch fermentation was initialized by using the batch fermentation. Various concentrations of glucose, yeast extract and soybean flour were employed to formulate the feeding medium. 330 unit/ml nattokinase was achieved after 48 h cultivation for the fed-batch fermentation.
The crude enzyme was stable at pH 6~7, and 65 % activity retained for the crude enzyme stored at 4 �aC for 1 month.
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Dorka, Penny. "Modelling Batch and Fed-batch Mammalian Cell Cultures for Optimizing MAb Productivity." Thesis, 2007. http://hdl.handle.net/10012/3166.
Full textAbstract:
The large-scale production of monoclonal antibodies (MAb) by mammalian cells in batch
and fed-batch culture systems is limited by the unwanted decline in cell viability and
reduced productivity that may result from changes in culture conditions. Therefore, it
becomes imperative to gain an in-depth knowledge of the factors affecting cell growth and cell viability that in turn determine the antibody production. An attempt has been made to obtain an overall model that predicts the behaviour of both batch and fed-batch systems as a function of the extra-cellular nutrient/metabolite concentrations. Such model formulation will aid in identifying and eventually controlling the dominant factors in play
to optimize monoclonal antibody (MAb) production in the future.
Murine hybridoma 130-8F producing anti-F-glycoprotein monoclonal antibody was grown in D-MEM medium (Gibco 12100) with 2% FBS. A systematic approach based on Metabolic Flux Analysis (MFA) was applied for the calculation of intracellular fluxes for
metabolites from available extracellular concentration values. Based on the set of
identified significant fluxes (from MFA), the original metabolic network was reduced to
a set of significant reactions. The reactions in the reduced metabolic network were then combined to yield a set of macro-reactions obeying Monod kinetics. Half saturation constants were fixed empirically to avoid computational difficulties that parameter estimation for an over-parameterized system of equations would cause. Using Quadratic Programming, the proposed Dynamic Model was calibrated and model prediction was carried out individually for batch and fed-batch runs. Flux distribution for batch and fedbatch
modes were compared to determine whether the same model structure could be applied to both the feeding profiles. Correlation analysis was performed to formulate a
Biomass Model for predicting cell concentration and viability as a function of the extracellular metabolite concentrations in batch and fed-batch experiments. Quadratic
Programming was applied once again for estimation of growth and death coefficients in the equations for viable and dead cell predictions. The prediction accuracy of these model equations was tested by using experimental data from additional runs. Further, the Dynamic Model was integrated with the Biomass Model to get an Integrated Model capable of predicting concentration values for substrates, extracellular metabolites, and viable and dead cell concentration by utilizing only starting concentrations as input.
It was found that even though the set of significant fluxes was the same for batch and fedbatch operations, the order of these fluxes was different between the two systems. There was a gradual metabolic shift in the fed-batch system with time indicating that under conditions of nutrient limitation, the available energy is channeled towards maintenance rather than growth. Also, available literature with regard to cell kinetics during fed-batch
operation suggests that under nutrient limited conditions, the cells move from a viable, non-apoptotic state to a viable apoptotic state. This is believed to lead to variations in antibody production rates and might explain inaccurate predictions for MAb obtained from the model proposed in the current work. As a result more detailed analysis of the system and in particular, the switch from non-apoptotic to apoptotic state is required.
As a continuation of efforts to study the system in-depth, fluorescence imaging is
currently being applied as a tool to capture the changes in cell morphology along the
course of experimental batch and fed-batch runs. These experiments maybe able to
elucidate the transition from non-apoptotic to apoptotic cells and this information maybe
used in the future to improve the accuracy of the existing mathematical model.