On-line monitoring of responses to nutrient feed additions by multi-frequency permittivity measurements in fed-batch cultivations of CHO cells

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DOIResolve DOI: http://doi.org/10.1007/s10616-010-9267-z
AuthorSearch for: ; Search for: ; Search for:
TypeArticle
Journal titleCytotechnology
Volume62
Issue2
Pages121132; # of pages: 12
Subjectactivity; Adenovirus; analysis; Animal; Bacillus thuringiensis; beta-Galactosidase; bio; Bioreactor; Biotechnology; Cell Culture; Cell Cycle; Cell Death; Cell Line; Cell Size; Cells; Characteristic frequency; CHO cell culture; CHO cells; Comparative Study; Fed-batch; Feeding strategy; Fermentation; Glucose; Heat; Hybridomas; I; insect cell; Insect cell culture; metabolism; methods; Nutrient; Oxygen; Permittivity; Physiological state; physiology; Protein; Recombinant protein; serum-free medium; Suspension culture; Virus production
AbstractChanges in the nutrient availability of mammalian cell cultures are reflected in the +¦ dispersion parameter characteristic frequency (fC) and the on-line dual frequency permittivity signal. Multifrequency permittivity measurements were therefore evaluated in fed-batch cultivations of two different CHO cell lines. Similar responses to nutrient depletions and discontinuous feed additions were monitored in different cultivation phases and experimental setups. Sudden increases in permittivity and fC occurred when feed additions were conducted. A constant or declining permittivity value in combination with a decrease in fC indicated nutrient limitations. fC correlated well with changes in oxygen uptake rate when cell diameter remained constant, indicating that metabolic activity is reflected in the value of fC. When significant cell size changes occurred during the cultivations, the analysis of the +¦-dispersion parameters was rendered complex. For the application of our findings in other systems it will be hence required to conduct additional off-line measurements. Based on these results, it is hypothesized that multi-frequency permittivity measurements can give information on the intracellular or physiological state in fed-batch mode. Similar observations were made when using different cell lines and feeding strategies, indicating that the findings are transferable to other cell lines and systems. The results should lead to an improved understanding of routine fed-batch processes. Additional studies are, however, required to explore how these observations can be used for fed-batch process development and optimization.
Publication date
LanguageEnglish
AffiliationNRC Biotechnology Research Institute; National Research Council Canada (NRC-CNRC)
Peer reviewedYes
NRC number52750
NPARC number16225343
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Record identifier3cc76011-d00e-47c0-a25f-920776c49d46
Record created2010-11-05
Record modified2016-05-09
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