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

Paper ID Volume ID Publish Year Pages File Format Full-Text
25750 43596 2006 17 PDF Available
Title
Constant specific growth rate in fed-batch cultivation of Bordetella pertussis using adaptive control
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 exponentially increasing demands for substrates and oxygen.

Keywords
Model-reference adaptive control; Biopharmaceuticals; Fed-batch cultivation; Specific growth rate; Dissolved oxygen; Bordetella pertussis
First Page Preview
Constant specific growth rate in fed-batch cultivation of Bordetella pertussis using adaptive control
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 125, Issue 2, 1 September 2006, Pages 252–268
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering