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Updated: Jul 8, 2026

Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation
Published on: May 18, 2020
Online automatic tuning and control for fed-batch cultivation
Zita I T A Soons1, Gerrit van Straten, Leo A van der Pol
1Systems and Control Group, Wageningen University, Wageningen, The Netherlands. zita.soons@wur.nl
Abstract:
Performance of controllers applied in biotechnological production is often below expectation. Online automatic tuning has the capability to improve control performance by adjusting control parameters. This work presents automatic tuning approaches for model reference specific growth rate control during fed-batch cultivation. The approaches are direct methods that use the error between observed specific growth rate and its set point; systematic perturbations of the cultivation are not necessary. Two automatic tuning methods proved to be efficient, in which the adaptation rate is based on a combination of the error, squared error and integral error. These methods are relatively simple and robust against disturbances, parameter uncertainties, and initialization errors. Application of the specific growth rate controller yields a stable system. The controller and automatic tuning methods are qualified by simulations and laboratory experiments with Bordetella pertussis.
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