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Computer programs for modeling mammalian cell batch and fed-batch cultures using logistic equations.
MedLine Citation:
PMID:  22241242     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A MATLAB(®) toolbox was developed for applying the logistic modeling approach to mammalian cell batch and fed-batch cultures. The programs in the toolbox encompass sensitivity analyses and simulations of the logistic equations in addition to cell specific rate estimation. The toolbox was first used to generate time courses of the sensitivity equations for characterizing the relationship between the logistic variable and the model parameters. Subsequently, the toolbox was used to describe CHO cell data from batch and fed-batch mammalian cell cultures. Cell density, product, glucose, lactate, glutamine, and ammonia data were analyzed for the batch culture while fed-batch analysis included cell density and product concentration. In all instances, experimental data were well described by the logistic equations and the resulting specific rate profiles were representative of the underlying cell physiology. The 6-variable batch culture data set was also used to compare the logistic specific rates with those from polynomial fitting and discrete derivative methods. The polynomial specific rates grossly misrepresented cell behavior in the initial and final stages of culture while those based on discrete derivatives had high variability due to computational artifacts. The utility of logistic specific rates to guide process development activities was demonstrated using specific protein productivity versus growth rate trajectories for the 3 cultures examined in this study. Overall, the computer programs developed in this study enable rapid and robust analysis of data from mammalian cell batch and fed-batch cultures which can help process development and metabolic flux estimation.
Authors:
Chetan T Goudar
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-13
Journal Detail:
Title:  Cytotechnology     Volume:  -     ISSN:  0920-9069     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8807027     Medline TA:  Cytotechnology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Cell Culture Development, Global Biological Development, Bayer HealthCare, 800 Dwight Way, Berkeley, CA, 94710, USA, chetan.goudar@bayer.com.
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