Analysis of the use of fortified medium in continuous culture of mammalian cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999

AUTHORS

Anshu Gambhir, Chun Zhang, Anna Europa, Wei-Shou Hu

ABSTRACT

Continuous culture is frequently used in the cultivation of mammalian cells for the manufacturing of recombinant protein pharmaceuticals. In such operations a large volume of medium is turned over each day, especially in the case where cell recycle, or perfusion cultivation, is practiced. In principle, the volumetric throughput of medium can be reduced by using a more concentrated feed while maintaining the same nutrient provision rate. Overall, the medium components are divided into two categories: ‘consumable nutrients' and ‘unconsumable inorganic bulk salts’. In such fortified medium, the concentrations of consumable nutrients, but not bulk salts, are increased. With a stoichiometrically-balanced medium, the large amount of nutrients fed into the culture is largely consumed by cells to give rise to residual concentrations of these nutrients in their optimal range. However, unless care is taken to initiate the continuous culture, overshoot of nutrients may occur during the transient period. The high nutrient concentration during overshoot may be inhibitory by itself, or the resulting high osmolality may retard the growth. Using a mathematical model that incorporates the growth inhibitory effect of high osmolality we demonstrate such a potentially catastrophic effect of nutrient and osmolality overshoot by simulation. To avoid overshoot a controlled nutrient feeding scheme should be devised at the initiation of continuous culture. More... »

PAGES

243-254

References to SciGraph publications

  • 1990-05. High density culture of hybridoma cells using a perfusion culture vessel with an external centrifuge in CYTOTECHNOLOGY
  • 1995-11. Hybridoma perfusion system using a sedimentation device in BIOTECHNOLOGY LETTERS
  • 1997-07. Alteration of mammalian cell metabolism by dynamic nutrient feeding in CYTOTECHNOLOGY
  • 1986-07. Production of human monoclonal antibodies by heterohybridomas in APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
  • 1993. Development of Instrumentation and Control Strategy in Bioreactor Culture of Hybridoma Cells in ANIMAL CELL TECHNOLOGY: BASIC & APPLIED ASPECTS
  • 1990-05. Industrial production of monoclonal antibodies and therapeutic proteins by dialysis fermentation in CYTOTECHNOLOGY
  • 1994-01. High density culture of mammalian cells with dynamic perfusion based on on-line oxygen uptake rate measurements in CYTOTECHNOLOGY
  • 1989-12. High cell density perfusion culture of mouse-human hybridomas in APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
  • 1993. High Cell Density Perfusion Culture of Hybridoma Cells for Production of Monoclonal Antibodies in the Celligen Packed Bed Reactor in ANIMAL CELL TECHNOLOGY: BASIC & APPLIED ASPECTS
  • 1993. Kinetics of Cell Metabolism and Antibody Production in High Concentration Perfusion Cultures in ANIMAL CELL TECHNOLOGY: BASIC & APPLIED ASPECTS
  • 1981-12. Oxygen demand and supply in cell culture in APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
  • 1996-05. Large-scale perfusion culture process for suspended mammalian cells that uses a centrifuge with multiple settling zones in APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1023/a:1008026613975

    DOI

    http://dx.doi.org/10.1023/a:1008026613975

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1030254704

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19003148


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