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The profile of the inner-tubing gas pressure for a tubular membrane aeration system was quantified. The correlations among the overall volumetric oxygen transfer coefficient (k[subscript L]a), the inner-tubing pressure, the tubing tightness, and the gas throughput are experimentally analyzed. A mathematical model was developed to describe the underlying phenomena. The results established the base for comparison with other aeration techniques. A novel method employing in situ laser imaging technology to monitor bubbles and cells, and analyze bubble size distributions in a micro-sparged bioreactor was developed. The effects of bioreactor operations on bubble size distributions were determined with following results: 1) Spargers with larger pores produced larger bubbles in most cases 2) Higher sparging rates resulted in bubble size increases up to 10% 3) Pluronic F68 shrank bubbles up to 30%. When the concentration of Pluronic F68 exceeded 1 g/L, no additional impact was observed. 4) Emulsion silicone antifoam up to 25 ppm had no impact on bubbles 5) Cell density (up to 22x10��� cells/mL) or culture age has no effect on bubble sizes In multiple 1 5-L long-term high-density cultures of animal cells, the correlations between sparging rate and cell damage for using 0.5 ��m and 15 ��m-pore spargers were quantified. At cell density of 2x10��� cells/mL, sparging above 0.025 vvm using the 0.5-��m sparger was detrimental to cells, while 0.054 vvm was detrimental for the 15-��m sparger. A model was developed to predict the rate of cell death resulted from cell-bubble interactions for high-density industrial animal cell cultures. The effect of high superficial velocity of sparging gas on cells at the sparger surface proved insignificant. A new dissolved CO��� sensor proved to be reliable for long-term use in industrial perfusion cell cultures. A novel method for the control of dissolved CO��� while simultaneously maintaining DO��� and pH setpoints was developed. The continuous control of dissolved CO���, DO��� and pH is achieved by simultaneously adjusting the total sparging rate as well as the ratio of O���, N��� and CO��� gas contents. This control strategy enables optimization of dissolved CO��� in industrial culture processes and allows for improved cell growth and protein production. / Graduation date: 2002

Thesis (M.S.)--Ohio University, March, 1994. / Title from PDF t.p.

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Thesis (M.S.)--California Polytechnic State University, 2008. / Major professor: Robert S. Crockett, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Engineering." "May 2008." Includes bibliographical references (leaves 38-45). Also available on microfiche (1 sheet).

A common problem observed in large-scale cell cultivation is reduced culture performance compared with small-scale processes due to the existence of concentration gradients caused by poor mixing. Small-scale simulations using microbial cell suspensions have shown that circulation of cells through concentration gradients of oxygen, pH and glucose can result in reduction of cell growth and product formation similar to the effects observed in large-scale bioreactors. This study was aimed at using scale-down studies to investigate poor mixing in large-scale bioreactors used for suspended plant and animal cell culture. Two plant cell suspensions and a hybridoma cell line were used in this work. The range of oxygen transfer coefficients achieved in the hybridoma and plant suspensions were about 50???20 h-1 and 12???6 h-1, respectively. One-vessel simulation was developed to induce fluctuations of dissolved oxygen tension in a 2-L bioreactor using intermittent sparging of air and nitrogen. The effect of dissolved oxygen fluctuations on the cells was examined by comparing the performance of the cultures with those operated at constant dissolved oxygen tension. In the hybridoma suspension culture, only slight effects on cell growth were observed at circulation times above 300 s. No effect on the specific glucose uptake rate or antibody production was observed at the circulation times tested. Analysis of gene expression for selected hypoxia-related genes also suggested that the overall effect was limited. In plant cell suspensions, the specific growth rates and biomass yields on total sugar in the cultures under fluctuating dissolved oxygen tension were essentially the same as those at constant dissolved oxygen tension for both transgenic Nicotiana tabacum and Thalictrum minus. Under fluctuating dissolved oxygen tension, no effect on antibody accumulation was observed in transgenic N. tabacum suspensions, but a decrease in berberine accumulation was observed in T. minus. From the results, it can be concluded that only minimal effects due to the development of concentration gradients would be expected in large-scale bioreactors used for the cultivation of the hybridoma and plant cell suspensions tested in this work.