Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 355697
Title Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion bioreactor: Metabolic analysis
Author(s) Dalm, M.C.F.; Lamers, P.P.; Cuijten, S.M.R.; Tjeerdsma, A.M.; Grunsven, W.M.J. van; Tramper, J.; Martens, D.E.
Source Biotechnology Progress 23 (2007)3. - ISSN 8756-7938 - p. 560 - 569.
DOI https://doi.org/10.1021/bp060323k
Department(s) Bioprocess Engineering
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2007
Keyword(s) flux analysis - antibody productivity - continuous-culture - membrane cholesterol - cellular-metabolism - mass-spectrometry - amino-acids - density - growth - retention
Abstract For the development of optimal perfusion processes, insight into the effect of feed and bleed rate on cell growth, productivity, and metabolism is essential. In the here presented study the effect of the feed and bleed rate on cell metabolism was investigated using metabolic flux analysis. Under all tested feed and bleed rates the biomass concentration as calculated from the nitrogen balance (biomass-nitrogen) increased linearly with an increase in feed rate, as would be expected. However, depending on the size of the feed and bleed rate, this increase was attained in two different ways. At low feed and bleed rates (Region I) the increase was obtained through an increase in viable-cell concentration, while the cellular-nitrogen content remained constant. At high feed and bleed rates (Region II) the increase was attained through an increase in cellular-nitrogen content, while the cell concentration remained constant. Per gram biomass-nitrogen, the specific consumption and production rates of the majority of the nutrients and products were identical in both regions, as were most of the fluxes. The major difference between the two regions was an increased flux from pyruvate to lactate and a decreased flux of pyruvate toward citrate in region II. The decreased in-flux at the level of citrate can either be balanced by a decreased out-flux toward lipid biosynthesis leading to a lower fraction of lipids in the cell, by a decreased out-flux toward the citric acid cycle resulting in a decreased energy generation, or by a combination of these. Finally, the specific productivity increases less than the nitrogen content per cell in region II, which implies that for obtaining maximum production rates it is important to increase the cell density and not only the biomass density.
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