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Role of Different Bioreactor Types and Feeding Regimes in Polyhydroxyalkanoate Production
Published in Martin Koller, The Handbook of Polyhydroxyalkanoates, 2020
Geeta Gahlawat, Sujata Sinha, Guneet Kaur
For PHA production, fed-batch cultivations have been extensively studied with the aim of achieving high cell density; these cultures yield high PHA productivity and require low investment cost [48]. The fed-batch cultures are initiated as batch cultivation and after some time intermittent or continuous addition of nutrients is done to maintain optimum substrate concentration inside the bioreactor. The nutrient feed solution should be balanced enough with respect to substrate concentration and rate of feeding primarily to maintain the growth of the microorganisms at a specific growth rate and simultaneously eliminate the generation of inhibitory byproducts. Fed-batch cultures are usually carried out by the control of nutrient feeding with respect to dissolved oxygen content [49], culture pH values [50,51] or availability of residual carbon sources [51,52]. Reports are available in literature wherein mathematical models have also been used intelligently to selectively feed the fresh nutrients such as carbon and nitrogen during fed-batch fermentation [16,48,53].
Fed-Batch Culture Processes
Published in Wei-Shou Hu, Cell Culture Bioprocess Engineering, 2020
Fed-batch culture is the prevailing mode of cell culture in the final production of manufacturing recombinant proteins. It extends the cell growth and production periods, reaches high cell concentrations, and is operationally relatively simple. The design of the feed medium and the selection of the feeding strategy strongly influence the productivity of fed-batch culture. Compared to batch and continuous culture operations, cells in fed-batch cultures are subjected to wide variations in their chemical environment and are potentially physiologically different during different stages of their culture as well as in different runs. Enhanced process knowledge and better control of the chemical environment will enhance the consistency of product quality.
Cell Culture Process Validation Including Cell Bank Qualification
Published in James Agalloco, Phil DeSantis, Anthony Grilli, Anthony Pavell, Handbook of Validation in Pharmaceutical Processes, 2021
Anne B. Tolstrup, Steven I. Max, Denis Drapeau, Timothy S. Charlebois
Currently, the most prevalent manufacturing mode by far for large biopharmaceuticals including monoclonal antibodies is fed-batch culture, although perfusion and continuous processing are becoming more popular, too, these years. In fed-batch, production cells are expanded through several seed train stages in vessels of increasing size prior to inoculation of the production bioreactor. The cells are further expanded here while the culture is supplied with nutrient feeds at specified time points. A temperature reduction to <37°C is often done after 4–6 days of exponential growth, after which the main recombinant protein production phase starts. The entire content of the production bioreactor is harvested as cell viability drops or productivity levels out, typically after about two weeks. Fed-batch processes are most often associated with a single thaw from a MCB or WCB according to a one-vial-one-run concept, although some companies do maintain prolonged seed bioreactor cultures for staggered inoculation of the production bioreactors. Perfusion cultures are also initiated by a cell expansion after cell bank vial thaw, but the production stage involves maintenance of a constant working volume in the bioreactor by continuous introduction of fresh culture medium and removal of spent medium through the use of a scalable cell retention system. Perfusion systems allow for extended culture durations (several weeks or months) and continuous harvest and purification operations. Variations to the perfusion mode, such as N-1 perfusion culture systems in which the cell culture inoculum is grown to high cell density in a seed bioreactor prior to inoculation of the production tank at high VCD, are also employed.
Bioethanol production from sugarcane molasses with supplemented nutrients by industrial yeast
Published in Biofuels, 2023
Hasan Shahriar Raby, Md Anowar Saadat, Ahmed Nazmus Sakib, Fatema Moni Chowdhury, Abu Yousuf
In order to achieve high productivity and high cell density in fed-batch culture, an exponential feeding strategy has been recognized as a potential pathway [38]. This strategy involves continuously feeding the culture with nutrients at an exponentially increasing rate, which can help to sustain rapid cell growth and maintain favorable conditions for optimal productivity. By providing nutrients in a controlled manner based on the growth rate of the cells, an exponential feeding strategy can enhance the efficiency of nutrient utilization, minimize nutrient limitations, and promote higher cell densities, ultimately leading to improved productivity in fed-batch cultures. Nutrients can be fed in an exponential method either at the beginning of the cell culture or can be distributed in a time interval. The current study applied the exponential feeding method by doubling and quadrupling the intake of nutrients. Growth supplements were fed during the initial stage of the batch culture.
Insight into the pilot‐scale fed-batch fermentation for production of Enterococcus faecium CW3801 using molasses-based medium
Published in Preparative Biochemistry & Biotechnology, 2022
Hock Wei Tang, Sahar Abbasiliasi, Zhang Jin Ng, Yee-Ying Lee, Teck-Kim Tang, Joo Shun Tan
The optimization results from CCD illustrated the maximum cell viability of E. faecium in a molasses-based medium was 29.4 × 1011 CFU/mL. The experimental model is reliable with high capability of prediction for the experimental data. This study demonstrated that molasses and yeast extract are good feedstock for the growth of E. faecium. However, work is currently in progress to test other nitrogen sources from wastes to replace with yeast extract to reduce fermentation costs. In a fed-batch fermentation process, final biomass concentration could be improved through the application of a stepwise feeding strategy instead of conventional constant a feeding strategy. Fed-batch cultivation provided higher cell viability as compared to batch cultivation due to the continuous supply of nutrient. Hence, a fed batch cultivation has an industrial potential for improvement of probiotic production. In future, different scale-up criteria need to be studied and applied such as constant Reynold’s number, constant impeller tip speed, constant power consumption per unit liquid volume (P/V constant) and constant volumetric oxygen transfer coefficients (Kla/k constant).
Control algorithms and strategies of feeding for fed-batch fermentation of Escherichia coli: a review of 40 years of experience
Published in Preparative Biochemistry & Biotechnology, 2021
Mohammad Mahmoodi, Ehsan Nassireslami
Differ from batch culture, in fed-batch culture fresh medium is added to a well-mixed fermenter according to a predetermined feed flow rate when the nutrients are about to run out. Thus the resulting cell concentration by this method of fermentation is usually higher than in a batch culture.[3] In this method of fermentation, growth curve maybe either exponential or other growth profiles, depending on the feeding strategy. In addition to higher biomass concentration, fed-batch culture superiority can be seen in a higher ultimate concentration of product as well as higher yield of product.[4]