Estimation of biomass concentrations in fermentation processes for recombinant protein production

Bioprocess and Biosystems Engineering
M JenzschA Lübbert

Abstract

Online biomass estimation for bioprocess supervision and control purposes is addressed. As the biomass concentration cannot be measured online during the production to sufficient accuracy, indirect measurement techniques are required. Here we compare several possibilities for the concrete case of recombinant protein production with genetically modified Escherichia coli bacteria and perform a ranking. At normal process operation, the best estimates can be obtained with artificial neural networks (ANNs). When they cannot be employed, statistical correlation techniques can be used such as multivariate regression techniques. Simple model-based techniques, e.g., those based on the Luedeking/Piret-type are not as accurate as the ANN approach; however, they are very robust. Techniques based on principal component analysis can be used to recognize abnormal cultivation behavior. For the cases investigated, a complete ranking list of the methods is given in terms of the root-mean-square error of the estimates. All techniques examined are in line with the recommendations expressed in the process analytical technology (PAT)-initiative of the FDA.

References

Nov 19, 2005·Journal of Biotechnology·Marco JenzschAndreas Luebbert
Feb 7, 2008·IEEE Transactions on Neural Networks·J Nie, S Haykin

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Citations

Aug 15, 2009·Applied Microbiology and Biotechnology·S GnothA Lübbert
May 10, 2012·Applied Microbiology and Biotechnology·Moira Monika Schuler, Ian William Marison
Oct 6, 2007·Bioprocess and Biosystems Engineering·Stefan GnothAndreas Lübbert
Aug 30, 2008·Bioprocess and Biosystems Engineering·A C A VelosoE C Ferreira
Apr 9, 2008·Journal of Industrial Microbiology & Biotechnology·Kristiina KiviharjuTero Eerikäinen
Apr 27, 2010·Trends in Biotechnology·Krist V GernaeyGürkan Sin
Apr 28, 2009·Biotechnology Journal·Krist V GernaeyGürkan Sin
Oct 1, 2011·Biotechnology and Bioengineering·F DavidM Di Berardino
Jun 20, 2012·Biotechnology and Bioengineering·Markus LuchnerGerald Striedner
Jun 2, 2015·Biotechnology Advances·V LooserK Kovar
Aug 1, 2015·Biotechnology Journal·Rimvydas Simutis, Andreas Lübbert
Sep 28, 2017·Bioengineering·Rimvydas Simutis, Andreas Lübbert
Feb 2, 2019·Preparative Biochemistry & Biotechnology·Ahmad BeirotiDariush Norouzian

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