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Bioreactor Scale (bioreactor + scale)
Selected AbstractsAxial Distribution of Oxygen Concentration in Different Airlift Bioreactor Scales: Mathematical Modeling and SimulationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 9 2006H. Znad Abstract Steady and unsteady state oxygen concentration distributions in the liquid and gas phases along the axial direction of different airlift bioreactor scales have been simulated for various gas flow rates and oxygen consumption rates by applying the axial dispersion model to the riser and the downcomer, and a complete mixing model for the top (separator) and the bottom sections of the bioreactor. The results show that the dissolved oxygen concentration is very low at the lower part of the downcomer when the rate of oxygen consumption by microorganisms is very high. Furthermore, the shorter (small) bioreactor shows relatively more uniform axial dissolved oxygen concentrations than the longer (large) bioreactor, due to the effect of the hydrostatic pressure along the bioreactor. One of the most important geometric factors for mass transfer is the reactor height, which dominates the mean pressure and thus influences the saturation concentration and mass transfer driving force. The presented model can be applied for modeling and scale-up of practical airlift bioreactors. [source] Evaluation of a novel Bacillus strain from a north-western Spain hot spring as a source of extracellular thermostable lipaseJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 10 2009Francisco J. Deive Abstract BACKGROUND: Thermophilic microorganisms are receiving significant attention as a source of useful thermostable enzymes. However, the number of known strains is still limited, and very often their most interesting biocatalysts are intracellular or membrane-bound and produced at low levels. Thus, the isolation and study of novel extracellular enzyme-producing thermophilic microorganisms is very interesting. Moreover, the assessment of bioreactor performance is crucial, given the scarce information on the large-scale culture of these strains. RESULTS: The production of a thermostable extracellular lipase in submerged cultures of a thermophilic microorganism, recently isolated in north-west Spain, was investigated. The strain was identified by 16S rDNA sequencing as belonging to genus Bacillus. The influence of operating variables (i.e. pH, temperature, aeration) on lipase biosynthesis was analysed. Enzyme production at bioreactor scale was investigated, special attention being paid to the effect of aeration and agitation rates. CONCLUSION: The best conditions for the studied process were determined in shake flasks as pH 7.0, 55 °C and high aeration levels. Also, the non-association between lipase production and cell growth was ascertained. The culture of this novel strain was successfully carried out in laboratory-scale bioreactors, thus proving its potential for further applications. Copyright © 2009 Society of Chemical Industry [source] NS0 cell damage by high gas velocity sparging in protein-free and cholesterol-free culturesBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2008Ying Zhu Abstract Recent developments in high cell density and high productivity fed-batch animal cell cultures have placed a high demand on oxygenation and carbon dioxide removal in bioreactors. The high oxygen demand is often met by increasing agitation and sparging rates of air/O2 in the bioreactors. However, as we demonstrate in this study, an increase of gas sparging can result in cell damage at the sparger site due to high gas entrance velocities. Previous studies have showed that gas bubble breakup at the culture surface was primarily responsible for cell damage in sparged bioreactors. Such cell damage can be reduced by use of surfactants such as Pluronic F-68 in the culture. In our results, where NS0 cells were grown in a protein-free and cholesterol-free medium containing 0.5 g/L Pluronic F-68, high gas entrance velocity at the sparger site was observed as the second mechanism for cell damage. Experiments were performed in scaled-down spinners to model the effect of hydrodynamic force resulting from high gas velocities on antibody-producing NS0 cells. Cell growth and cell death were described by first-order kinetics. Cell death rate constant increased significantly from 0.04 to 0.18 day,1 with increasing gas entrance velocity from 2.3 to 82.9 m/s at the sparger site. The critical gas entrance velocity for the NS0 cell line studied was found to be ,30 m/s; velocities greater than 30 m/s caused cell damage which resulted in reduced viability and consequently reduced antibody production. Observations from a second cholesterol-independent NS0 cell line confirmed the occurrence of cell damage due to high gas velocities. Increasing the concentration of Pluronic F-68 from 0.5 to 2 g/L had no additional protective effect on cell damage associated with high gas velocity at the sparger. The results of gas velocity analysis for cell damage have been applied in two case studies of large-scale antibody manufacturing. The first is a troubleshooting study for antibody production carried out in a 600 L bioreactor, and the second is the development of a gas sparger design for a large bioreactor scale (e.g., 10,000 L) for antibody manufacturing. Biotechnol. Bioeng. 2008;101: 751,760. © 2008 Wiley Periodicals, Inc. [source] Control of misincorporation of serine for asparagine during antibody production using CHO cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2010Anurag Khetan Abstract A recombinant monoclonal antibody produced by Chinese hamster ovary (CHO) cell fed-batch culture was found to have amino acid sequence misincorporation upon analysis by intact mass and peptide mapping mass spectrometry. A detailed analysis revealed multiple sites for asparagine were being randomly substituted by serine, pointing to mistranslation as the likely source. Results from time-course analysis of cell culture suggest that misincorporation was occurring midway through the fed-batch process and was correlated to asparagine reduction to below detectable levels in the culture. Separate shake flask experiments were carried out that confirmed starvation of asparagine and not excess of serine in the medium as the root cause of the phenomenon. Reduction in serine concentration under asparagine starvation conditions helped reduce extent of misincorporation. Supplementation with glutamine also helped reduce extent of misincorporation. Maintenance of asparagine at low levels in 2,L bench-scale culture via controlled supplementation of asparagine-containing feed eliminated the occurrence of misincorporation. This strategy was implemented in a clinical manufacturing process and scaled up successfully to the 200 and 2,000,L bioreactor scales. Biotechnol. Bioeng. 2010;107: 116,123. © 2010 Wiley Periodicals, Inc. [source] Axial Distribution of Oxygen Concentration in Different Airlift Bioreactor Scales: Mathematical Modeling and SimulationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 9 2006H. Znad Abstract Steady and unsteady state oxygen concentration distributions in the liquid and gas phases along the axial direction of different airlift bioreactor scales have been simulated for various gas flow rates and oxygen consumption rates by applying the axial dispersion model to the riser and the downcomer, and a complete mixing model for the top (separator) and the bottom sections of the bioreactor. The results show that the dissolved oxygen concentration is very low at the lower part of the downcomer when the rate of oxygen consumption by microorganisms is very high. Furthermore, the shorter (small) bioreactor shows relatively more uniform axial dissolved oxygen concentrations than the longer (large) bioreactor, due to the effect of the hydrostatic pressure along the bioreactor. One of the most important geometric factors for mass transfer is the reactor height, which dominates the mean pressure and thus influences the saturation concentration and mass transfer driving force. The presented model can be applied for modeling and scale-up of practical airlift bioreactors. [source] | ||||||||||