Chapter 18. Mixing in the Fermentation and Cell Culture Industries

  1. Edward L. Paul3,
  2. Victor A. Atiemo-Obeng4,
  3. Suzanne M. Kresta5
  1. Ashraf Amanullah1,
  2. Barry C. Buckland1,
  3. Alvin W. Nienow2

Published Online: 30 JAN 2004

DOI: 10.1002/0471451452.ch18

Handbook of Industrial Mixing: Science and Practice

Handbook of Industrial Mixing: Science and Practice

How to Cite

Amanullah, A., Buckland, B. C. and Nienow, A. W. (2004) Mixing in the Fermentation and Cell Culture Industries, in Handbook of Industrial Mixing: Science and Practice (eds E. L. Paul, V. A. Atiemo-Obeng and S. M. Kresta), John Wiley & Sons, Inc., Hoboken, NJ, USA. doi: 10.1002/0471451452.ch18

Editor Information

  1. 3

    Merck & Co., Inc. (retired); 308 Brooklyn Boulevard, Sea Girt, NJ 08750, USA

  2. 4

    The Dow Chemical Company, Building 1776, Midland, MI 48674, USA

  3. 5

    Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada T6G 2G6

Author Information

  1. 1

    Merck Research Laboratories, Merck & Co., Inc., WP26C-1 101, 770 Sumneytown Pike, West Point, PA 19438, USA

  2. 2

    Department of Chemical Engineering, School of Engineering, University of Birmingham, Edgbaston, Birmingham B15 2JJ, United Kingdom

Publication History

  1. Published Online: 30 JAN 2004
  2. Published Print: 14 NOV 2003

ISBN Information

Print ISBN: 9780471269199

Online ISBN: 9780471451457

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Keywords:

  • mixing;
  • mass transfer;
  • aeration;
  • impeller design;
  • scale-up;
  • scale-down;
  • bacterial physiology;
  • recombinant protein;
  • rheologically-complex fermentations;
  • fungal fermentations;
  • morphology;
  • hyphal fragmentation;
  • animal cell culture;
  • plant cell culture;
  • cell damage

Summary

Applications of mixing technology in the fermentation and cell culture industries are discussed. The limitations of traditional scale-up methods using stirred tank bioreactors have been highlighted and alternative methods using a scale-down approach that simulate the micro-environment (substrate, dissolved oxygen and pH) experienced by cells at the large scale are described. Problems of bulk mixing and mass transfer inherent in rheologically complex polysaccharide fermentations are addressed using Xanthan gum as a model system. The effects of agitation intensity on hyphal morphology and product formation in two commercially important fungal fermentations, as well as on bacterial physiology, are discussed. In addition, a review of damage mechanisms related to agitation intensity and aeration in cell culture applications and guidelines for successful operation of large scale cell culture bioreactors are provided. Finally the issues related to hydrodynamic damage in plant cell cultures are briefly discussed.