Abstract
A stationary bubble-swarm has been used to aerate a mammalian cell culture bioreactor with an extremely low gas flow rate. Prolonging the residence time of the gas bubbles within the medium improved the efficiency of the gas transfer into the liquid phase and suppressed foam formation. An appropriate field of speed gradients prevented the bubbles from rising to the surface. This aeration method achieves an almost 90% transfer of oxygen supplied by the bubbles. Consequently, it is able to supply cells with oxygen even at high cell densities, while sparging with a gas flow of only 0.22·10−3–1.45·10−3 vvm (30–200 ml/h).
The reactor design, the oxygen transfer rates and the high efficiency of the system are presented. Two repeated batch cultures of a rat-mouse hybridoma cell line are compared with a surface-aerated spinner culture. The used cell culture medium was serum-free, either with or without BSA and did not contain surfactants or other cell protecting agents. One batch is discussed in detail for oxygen supply, amino acid consumption and specific antibody production.
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References
Büntemeyer H, Lütkemeyer D and Lehmann J (1991) Optimization of serum-free fermentation processes for antibody production. Cytotechnology 5: 57–67.
Handa A, Emery AN and Spier RE (1985) On the evaluation of gas-liquid interfacial effects on hybridoma viability in bubble column bioreactors. Develop. Biol. Standard. 66: 241–253.
Handa-Corrigan A, Emery AN and Spier RE (1989) Effect of gas-liquid interfaces on the growth of suspended mammalian cells: mechanisms of cell damage by bubbles. Enzyme Microb. Technol. 11: 230–235.
Heidemann R, Riese U, Lütkemeyer D, Büntemeyer H and Lehmann J (1994) The Super-Spinner: a low cost animal cell culture bioreactor for the CO2, incubator. Cytotechnology 14: 1–9.
Hülscher M and Onken U (1988) Influence of bovine serum albumin on the growth of hybridoma cells in airlift loop reactors using serum-free medium. Biotechnology Letters 10: 689–694.
Jäger V, Lehmann J and Friedl P (1988) Serum-free growth medium for the cultivation of a wide spectrum of mammalian cells in stirred bioreactors. Cytotechnology 1: 319–329.
Jäger V (1991) Serum-free media suitable for upstream and down-stream processing. In: Spier RE, Griffiths JB, Meignier B (eds.) Production of Biologicals from Animal Cells in Culture. Research, Development and Achievements. Butterworths, Kent, UK.
Jöbes I, Martens D and Tramper J (1991) Lethal events during gas sparging in animal cell culture. Biotechnol. Bioeng. 37: 484–490.
Lehmann J, Heidemann R, Riese U, Lütkemeyer D and Büntemeyer H (1992) Der Superspinner. Ein ‘Brutschrank-Fermenter’ für die Massenkultur tierischer Zellen. Bioengineering 5+6: 36–38.
Oh SKW, Nienow AW, Al-Rubeai M and Emery AN (1992) Further studies of the culture of mouse hybridomas in an agitated bioreactor with and without continuous sparging. J. Biotechnol. 22: 245–270.
Ozturk SS and Palsson BO (1991) Examination of serum and bovine serum albumin as shear protective agents in agitated cultures of hybridoma cells. J. Biotechnol. 18: 13–28.
Prins A and van't Riet K (1987) Proteins and surface effects in fermentation: foam, antifoam and mass transfer. Tibtech 5: 296–301.
Spier RE, Griffiths JB (1984) An examination of the data and concepts germane to the oxygenation of cultured animal cells. Dev. Biol. Standard. 55: 81–92.
Zhang S, Handa-Corrigan A and Spier RE (1992) Foaming and media surfactant effects on the cultivation of animal cells in stirred and sparged bioreactors. J. Biotechnol. 25: 289–306.
Zhang S, Handa-Corrigan A and Spier RE (1992) Oxygen transfer properties of bubbles in animal cell culture. Biotechnol. Bioeng. 40: 252–259.
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Gudermann, F., Lütkemeyer, D. & Lehmann, J. Design of a bubble-swawm bioreactor for animal cell culture. Cytotechnology 15, 301–309 (1994). https://doi.org/10.1007/BF00762405
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DOI: https://doi.org/10.1007/BF00762405