Abstract
This work describes a novel bioreactor system for the cultivation of animal, insect, and plant cells using wave agitation induced by a rocking motion. This agitation system provides good nutrient distribution, off-bottom suspension, and excellent oxygen transfer without damaging fluid shear or gas bubbles. Unlike other cell culture systems, such as spinners, hollow-fiber bioreactors, and roller bottles, scale-up is simple, and has been demonstrated up to 100 L of culture volume. The bioreactor is disposable, and therefore requires no cleaning or sterilization. Additions and sampling are possible without the need for a laminar flow cabinet. The unit can be placed in an incubator requiring minimal instrumentation. These features dramatically lower the purchase cost, and operating expenses of this laboratory/pilot scale cell cultivation system. Results are presented for various model systems: 1) recombinant NS0 cells in suspension; 2) adenovirus production using human 293 cells in suspension; 3) Sf9 insect cell/baculovirus system; and 4) human 293 cells on microcarrier. These examples show the general suitability of the system for cells in suspension, anchorage-dependent culture, and virus production in research and GMP applications.
Keywords: bioreactor, cell culture, disposable, wave agitation
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References
- Aunins JG, Woodson BA, Hale TK, Wang DIC. Effects of paddle impeller geometry on power input and mass transfer in small-scale animal cell culture vessels. Biotechnol Bioeng. 1989;34:11270–1132. doi: 10.1002/bit.260340902. [DOI] [PubMed] [Google Scholar]
- Dorresteijn RC, de Gooijer CD, Tramper J, Beuvery EC. A simple dynamic method for on-line determination of kLa during cultivation of animal cells. Biotechnol Techniques. 1994;8(9):675–680. doi: 10.1007/BF00241697. [DOI] [Google Scholar]
- Fleischaker RJ, Sinsky AJ. Oxygen demand and supply in cell culture. Eur J Appl Microbiol Biotechnol. 1981;12:193–197. doi: 10.1007/BF00499486. [DOI] [Google Scholar]
- Kybal J, Sikyta B. A device for cultivation of plant and animal cells. Biotechnology Letters. 1985;7:467–470. doi: 10.1007/BF01199860. [DOI] [Google Scholar]
- Hu WS, Meier J, Wang DIC. Use of surface aerator to improve oxygen transfer in cell culture. Biotechnol Bioeng. 1986;28:122–125. doi: 10.1002/bit.260280120. [DOI] [PubMed] [Google Scholar]
- Singh V. On-Line measurement of oxygen uptake in cell culture using the dynamic method. Biotechnol Bioeng. 1996;52:443–448. doi: 10.1002/(SICI)1097-0290(19961105)52:3<443::AID-BIT12>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]