Constant specific growth rate in fed-batch cultivation of Bordetella pertussis using adaptive control

Journal of Biotechnology
Zita I T A SoonsAnton J B van Boxtel

Abstract

Monitoring and control of production processes for biopharmaceuticals have become standard requirements to support consistency and quality. In this paper, a constant specific growth rate in fed-batch cultivation of Bordetella pertussis is achieved by a newly designed specific growth rate controller. The performance of standard control methods is limited because of the time-varying characteristics due to the exponentially increasing biomass and volume. To cope with the changing dynamics, a stable model reference adaptive controller is designed which adapts the controller settings as volume and biomass increase. An important asset of the design is that dissolved oxygen is the only required online measurement. An original design without considering the dissolved oxygen dynamics resulted experimentally in oscillatory behaviour. Hence, in contrast to common believes, it is essential to include dissolved oxygen dynamics. The robustness of this novel design was tested in simulation. The validity of the design was confirmed by laboratory experiments for small-scale production of B. pertussis. The controller was able to regulate the specific growth rate at the desired set point, even during a long fed-batch cultivation time with exponen...Continue Reading

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 12, 2007·Bioprocess and Biosystems Engineering·Stefan GnothAndreas Lübbert
Oct 6, 2007·Bioprocess and Biosystems Engineering·Stefan GnothAndreas Lübbert
Dec 19, 2007·Journal of Industrial Microbiology & Biotechnology·Wei ZhaoXunzhang Wang
Aug 1, 2008·Bioprocess and Biosystems Engineering·Zita I T A SoonsAnton J B van Boxtel
Dec 25, 2007·Bioprocess and Biosystems Engineering·Zita I T A SoonsAnton J B van Boxtel
Dec 12, 2012·Biotechnology Progress·Hector BudmanWalid Al-Gherwi
Aug 1, 2015·Biotechnology Journal·Rimvydas Simutis, Andreas Lübbert
Jul 20, 2020·Biotechnology Journal·Anne RichelleMoritz von Stosch

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