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Control of specific carbon dioxide production in a fed-batch culture producing recombinant protein using a soft sensor
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
2015 (English)In: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 200, 44-51 p.Article in journal (Refereed) Published
Abstract [en]

The feeding of a fed-batch cultivation producing recombinant protein was controlled by a soft sensor setup. It was assumed that the control approach could be based on the cells production of carbon dioxide and that this parameter indicates the metabolic state occurring at induced protein expression. The soft sensor used the on-line signals from a carbon dioxide analyser and a near-infrared (NIR) probe for biomass to estimate the specific production rate (q(CO2)). Control experiments were carried out with various q(CO2) set-points where we observe that the feeding of nutrients to the culture could easily be controlled and resulted in a decreased variability compared to uncontrolled cultivations. We therefore suggest that this control approach could serve as an alternative to other commonly applied methods such as controlling the cells overflow metabolism of acetate or the cells specific growth rate. However, further studies of the internal metabolic fluxes of CO2 during protein expression would be recommended for a more precise characterization of the relationship between q(CO2) and protein expression in order to fully interpret the control behaviour.

Place, publisher, year, edition, pages
Elsevier , 2015. Vol. 200, 44-51 p.
Keyword [en]
Reproducibility; Variance; Carbon dioxide production rate; Bioprocess regulation; Monitoring; Software sensor
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:liu:diva-117361DOI: 10.1016/j.jbiotec.2015.02.030ISI: 000352017700009PubMedID: 25746902OAI: oai:DiVA.org:liu-117361DiVA: diva2:807872
Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2015-04-24

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Gustavsson, RobertMandenius, Carl-Fredrik
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