Nutrient Optimization for the Production of Biologicals from Animal Cells Cultured at High Density

  • David W. Jayme
  • Stefan A. Weiss


The formulation components necessary to maintain animal cells in vitro at high density for biological production may differ quantitatively and qualitatively from the nutrient requirements for routine cell cultivation at low densities. Elimination of serum to facilitate downstream processing and regulatory approval necessitates compensation for the nutritional and biophysical roles of serum in the cell culture environment. Biochemical analysis of spent culture effluents from high density bioreactors offers a helpful insight to the unique nutrient requirements of that specialized system and permits iterative optimization of serum-free, synthetic medium composition to sustain bioreactor productivity. This information may be exploited, either by enhancing the nutrient levels of the basal medium or by providing nutritional supplementation of exhausted metabolites via batch or perfusion feeding of liquid concentrates. This paper focuses upon techniques utilized in this laboratory to assess bioreactor depletion of amino acids, carbohydrates and lipids. These data are applied to the design of serum-free media for biopharmaceutical and biotechnological applications of hybridomas, recombinant CHO cells, and invertebrate cells.


Chinese Hamster Ovary Cell Maximal Cell Density Culture Expansion Monoclonal Antibody Production BACULOVIRUS Expression Vector System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Airey P, Benny G, Swartzwelder F and Conrad D (1991) “A novel lipid rich albumin supplement for serum-free cell culture.” Focus 13: 2–7.Google Scholar
  2. Cohn EJ, Strong LE, Hughes WL Jr, Mulford DJ, Ashworth JN, Melin M & Taylor HL (1946) “Preparation and properties of serum and plasma proteins: a system for the separation into fractions of protein and lipoprotein components of biological tissues and fluids.” J. Amer. Chem. Soc. 68: 459–475.CrossRefGoogle Scholar
  3. Freshney RI (1987) Culture of animal cells: a manual of basic technique (2nd edition). Liss, New York.Google Scholar
  4. Gorfien S and Weiss SA (1990) “A new, serum-free medium for growth of Chinese hamster ovary (CHO) cells in suspension.” Focus 12(3): 75–76.Google Scholar
  5. Jayme DW (1991) “Nutrient optimization for high density biological production applications.” Cytotechnology (in press).Google Scholar
  6. Jayme DW (1990) “Alternatives to fetal bovine serum for mammalian cell culture.” Focus 12: 3–8.Google Scholar
  7. Jayme DW & Blackman KE (1985) “Culture media for propagation of mammalian cells, viruses, and other biologicals.” In: Mizrahi A and van Wezel AL (eds.) Advances in Biotechnological Processes. Vol. 5 (pp. 1–30) Liss, New York.Google Scholar
  8. Ogden G & Foldi P (1987) “Amino acid analysis: an overview of current methods.” LC-GC 5: 28–40.Google Scholar
  9. Prior CP, Doyle KR, Duffy SA, Hope JA, Moellering BJ, Prior GM, Scott RW & Tolbert WR (1989) “The recovery of highly purified biopharmaceuticals from perfusion cell culture bioreactors.” J. Parent. Sci. Tech. 43: 15–23.Google Scholar
  10. Spector AA (1972) “Fatty acid, glyceride, and phospholipid metabolism.” In: Rothblat GH and Cristofalo VJ (eds.) Growth, Nutrition, and Metabolism of Cells in Culture. Vol. II (pp. 257–298) Academic, New York.CrossRefGoogle Scholar
  11. Weiss SA, Lester TL, Kalter SS and Vaughn JL (1980) “Chemically Defined Serum-Free Media for the Cultivation of Primary Cells and Their Susceptibility to Viruses.” In Vitro 16: 616–628.PubMedCrossRefGoogle Scholar
  12. Weiss SA, Gorfien S, Fike R, DiSorbo D and Jayme D (1990) “Large Scale Production of Proteins Using Serum-Free Insect Cell Culture.” Proceedings of the Ninth Australian Biotechnology Conference, In: Biotechnology: The Science and the Business, pp. 220–231.Google Scholar
  13. Weiss SA, Belisle BW, DeGiovanni A, Godwin G, Kohler J and Summers MD (1989) “Insect Cells as Substrates for Biologicals.” In: Proceeding of a Conference on Biotechnology, Biological Pesticides and Novel Plant - Pest Resistance for Pest Management. DW Roberts and RR Granados, eds., Boyce Thompson Institute for Plant Research, Ithaca, NY, pp. 271–189.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1991

Authors and Affiliations

  • David W. Jayme
    • 1
  • Stefan A. Weiss
    • 1
  1. 1.Cell Culture Research and Development LaboratoryGIBCO/Life Technologies, Inc.Grand IslandUSA

Personalised recommendations