Document Detail

Adapted ultra scale-down approach for predicting the centrifugal separation behavior of high cell density cultures.
MedLine Citation:
PMID:  17949106     Owner:  NLM     Status:  MEDLINE    
The work presented here describes an ultra scale-down (USD) methodology for predicting centrifugal clarification performance in the case of high cell density fermentation broths. Existing USD approaches generated for dilute systems led to a 5- to 10-fold overprediction of clarification performance when applied to such high cell density feeds. This is due to increased interparticle forces, leading to effects such as aggregation, flocculation, or even blanket sedimentation, occurring in the low shear environment of a laboratory centrifuge, which will not be apparent in the settling region of a continuous-flow industrial centrifuge. A USD methodology was created based upon the dilution of high solids feed material to approximately 2% wet wt/vol prior to the application of the clarification test. At this level of dilution cell-cell interactions are minimal. The dilution alters the level of hindered settling in the feed suspensions, and so mathematical corrections are applied to the resultant clarification curves to mimic the original feed accurately. The methodology was successfully verified: corrected USD curves accurately predicted pilot-scale clarification performance of high cell density broths of Saccharomyces cerevisiae and Escherichia coli cells. The USD method allows for the rapid prediction of large-scale clarification of high solids density material using millilitre quantities of feed. The advantages of this method to the biochemical engineer, such as the enabling of rapid process design and scale-up, are discussed.
Andrew D Tustian; Heidi Salte; Nicholas A Willoughby; Inass Hassan; Michael H Rose; Frank Baganz; Michael Hoare; Nigel J Titchener-Hooker
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-20
Journal Detail:
Title:  Biotechnology progress     Volume:  23     ISSN:  8756-7938     ISO Abbreviation:  Biotechnol. Prog.     Publication Date:    2007 Nov-Dec
Date Detail:
Created Date:  2007-12-07     Completed Date:  2008-03-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8506292     Medline TA:  Biotechnol Prog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1404-10     Citation Subset:  IM    
The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
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MeSH Terms
Cell Culture Techniques
Centrifugation / methods*
Escherichia coli / metabolism
Particle Size
Saccharomyces cerevisiae / metabolism

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