Abstract
A new method of making microcapsules with calcium alginate gel was developed and the cultivation of the encapsulated hybridoma cells producing monoclonal antibodies against human chorionic gonadotropin was investigated. A high cell density of 2.0×108 cells/cm3 in the capsules led to a high dilution rate of 0.68 per hour and resulted in the high volumetric monoclonal antibody productivity of 652.8 mg/l/day, which was 20–30 times higher than those of traditional continuous suspension cultures. However, long-term continuous culture was not achieved with this capsule system probably because of the limitation in nutrient supply and the accumulation of waste products. Also the analysis of oxygen transfer in this system showed that oxygen supply was not enough to support such a high cell density.
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References
Baily JE and Ollis DF (1986) Biochemical engineering fundamentals, 2nd ed., McGraw-Hill, New York.
Brunt JV (1986) Immobilized mammalian cells: the gentle way to productivity. Bio/Technology 4: 506–517.
Chang HN (1987) Membrane bioreactors: engineering aspects. Biotech. Adv. 5: 129–145.
Evans TL and Miller RA (1988) Large-scale production of murine monoclonal antibodies using hollow fiber bioreactors. Bio/Technology 6: 762–766.
Gharapetian H, Davies NA and Sun AM (1986) Encapsulation of viable cells within polyacrylate membranes. Biotechnol. Bioeng. 28: 1595–1600.
Heath C and Belfort G (1987) Immobilization of suspended mammalian cells: analysis of hollow fiber and microcapsule bioreactor. In: Advances in Biochemical Engineering/Biotechnology. Vol. 34 (pp. 1–31) Springer-Verlag.
Itamunoala GF (1987) Effective diffusion coefficients in calcium alginate gel. Biotechnol. Progress 3: 115–120.
Jo EC, Park HJ, Park JM and Kim KH (1991) Balanced nutrient fortification enables high-density hybridoma cell culture in batch culture. Biotechnol. Bioeng. 36: 717–722.
King GA, Daugulis AJ, Faulker P and Goosen MFA (1987) Alginate-polylysine microcapsules of controlled membrane molecular weight cutoff for mammalian cell culture engineering. Biotechnol. Progress 3: 231–240.
Lazar A, Silberstein L, Mizrahi A and Reuveny S (1988) An immobilized hybridoma culture perfusion system for production of monoclonal antibodies. Cytotechnology 1: 331–337.
Lim F and Sun AM (1980) Microencapsulated islets as bioartificial endocrine pancreas. Science 210: 908–910.
Linardos TI, Kalogerakis N, Behie LA and Lamontagne LR (1991) Canadian J. Chem. Eng. 69: 429–438.
Murakami H (1990) What should be focused in the study of cell culture technology for production of bioactive proteins. Cytotechnology 3: 3–7.
Nigam SC, Tsao IF, Sakoda A and Wang HY (1988) Techniques for preparing hydrogel membrane capsules. Biotechnol. Techniques 2: 271–276.
Oh DJ (1992) Ph.D Thesis, KAIST, Taejon, Korea.
Oh DJ and Chang HN (1992) High density culture of hybridoma cells in a dual hollow fiber bioreactor. Biotechnol. Techniques 6: 77–82.
Oh DJ and Chang HN (1992) Continuous production of hCG monoclonal antibody in various membrane bioreactors. In: Proc. of 9th International Biotechnology Symposium and Exposition (pp. 563–567).
Posillico EG (1986) Microencapsulation technology for largescale antibody production. Bio/Technology 4: 114–117.
Putnam JE (1987) Monoclonal antibody production in a ceramic matrix. In: Commercial production of monoclonal antibodies: a guide for scale-up. (pp. 119–138) Marcel Dekker New York.
Spiekermann P, Vorlop KD and Klein J (1987) Animal cells encapsulated within Ca-alginate hollow-spheres. In: Proc. 4th European Congress on Biotechnology 3: 590–593.
Sun Y, Furusaki S, Yamauchi A and Ichimura K (1989) Diffusivity of oxygen into carriers entrapping whole cells. Biotechnol. Bioeng. 34: 55–58.
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Oh, D.J., Choi, S.K., Chang, H.N. et al. Production of monoclonal antibodies against human chorionic gonadotropin by hybridoma cultures in calcium alginate capsules. Cytotechnology 13, 41–49 (1993). https://doi.org/10.1007/BF00749974
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DOI: https://doi.org/10.1007/BF00749974