LAPSE:2026.0291
Published Article

LAPSE:2026.0291
Automatic kLa determination in stirred tank reactors by model-based design of experiments
June 12, 2026
Abstract
The volumetric gas-liquid mass transfer coefficient (kLa) is a key performance parameter in stirred tank reactors and is commonly determined through extensive experiments across the operational space. This work presents an automatic, closed-loop framework for kLa determination based on model-based design of experiments (MBDoE), in which agitation and aeration inputs are adapted in real time.During each experiment, dissolved oxygen data is collected and used to estimate the parameters of a Van't Riet kLa relation. The parameter uncertainty is quantified using the covariance matrix, and the experiments are iteratively selected based on D-optimality or E-optimality MBDoE, until a threshold of RSEi < 0.15 is reached for all parameters. The MBDoE approach is evaluated through repeated runs and compared against random designs, full factorial (FF) design, and a full grid design.The results demonstrate that the closed-loop MBDoE framework can significantly reduce the number of experiments required to characterize kLa while maintaining accurate predictions of gas-liquid mass transfer over the design space. D-optimal MBDoE converges in fewer than four experiments on average, while E-optimal MBDoE converges in less than six experiments on average, translating into approximately a 60% reduction of the number of experiments as compared to a full factorial DoE design.
The volumetric gas-liquid mass transfer coefficient (kLa) is a key performance parameter in stirred tank reactors and is commonly determined through extensive experiments across the operational space. This work presents an automatic, closed-loop framework for kLa determination based on model-based design of experiments (MBDoE), in which agitation and aeration inputs are adapted in real time.During each experiment, dissolved oxygen data is collected and used to estimate the parameters of a Van't Riet kLa relation. The parameter uncertainty is quantified using the covariance matrix, and the experiments are iteratively selected based on D-optimality or E-optimality MBDoE, until a threshold of RSEi < 0.15 is reached for all parameters. The MBDoE approach is evaluated through repeated runs and compared against random designs, full factorial (FF) design, and a full grid design.The results demonstrate that the closed-loop MBDoE framework can significantly reduce the number of experiments required to characterize kLa while maintaining accurate predictions of gas-liquid mass transfer over the design space. D-optimal MBDoE converges in fewer than four experiments on average, while E-optimal MBDoE converges in less than six experiments on average, translating into approximately a 60% reduction of the number of experiments as compared to a full factorial DoE design.
Record ID
Keywords
Gas-liquid mass transfer, Model-based design of experiments, Modelling, Numerical Methods, Optimization, Stirred tank reactors
Subject
Suggested Citation
Caetano AHV, Gernaey KV, Kager J. Automatic kLa determination in stirred tank reactors by model-based design of experiments. Systems and Control Transactions 5:721-726 (2026) https://doi.org/10.69997/sct.115861
Author Affiliations
Caetano AHV: DTU, Department of Chemical and Biochemical Engineering, Kgs. Lyngby, Denmark [ORCID]
Gernaey KV: DTU, Department of Chemical and Biochemical Engineering, Kgs. Lyngby, Denmark [ORCID]
Kager J: DTU, Department of Chemical and Biochemical Engineering, Kgs. Lyngby, Denmark [ORCID]
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Gernaey KV: DTU, Department of Chemical and Biochemical Engineering, Kgs. Lyngby, Denmark [ORCID]
Kager J: DTU, Department of Chemical and Biochemical Engineering, Kgs. Lyngby, Denmark [ORCID]
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Journal Name
Systems and Control Transactions
Volume
5
First Page
721
Last Page
726
Year
2026
Publication Date
2026-06-12
Version Comments
Original Submission
Other Meta
PII: 0721-0726-447-SCT-5-2026, Publication Type: Journal Article
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LAPSE:2026.0291
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https://doi.org/10.69997/sct.115861
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[v1] (Original Submission)
Jun 12, 2026
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References Cited
- Garcia-Ochoa F, Gomez E. Bioreactor scale-up and oxygen transfer rate in microbial processes: an overview. Biotechnology Advances 27:153-176 (2009) https://doi.org/10.1016/j.biotechadv.2008.10.006
- Schaepe S, Kuprijanov A, Sieblist C, Jenzsch M, Simutis R, Lübbert A. Kla of stirred tank bioreactors revisited. Journal of Biotechnology 168:576-583 (2013) https://doi.org/10.1016/j.jbiotec.2013.08.032
- Aroniada M, Maina S, Koutinas A, Kookos IK. Estimation of volumetric mass transfer coefficient (kla)-review of classical approaches and contribution of a novel methodology. Biochemical Engineering Journal 155:107458 (2020) https://doi.org/10.1016/j.bej.2019.107458
- Franceschini G, Macchietto S. Model-based design of experiments for parameter precision: state of the art. Chemical Engineering Science 63:4846-4872 (2008) https://doi.org/10.1016/j.ces.2007.11.034
- Van't Riet, K. Review of Measuring Methods and Results in Nonviscous Gas-Liquid Mass Transfer in Stirred Vessels Introduction Stirred vessels are frequently employed to achieve a. Ind. Eng. Chem. Process Des. Dev 18, 357 (1979).
- Heinrich M, Arutjunjan R, Timmer J. On the different flavours of practical identifiability. Current Opinion in Systems Biology 42:100556 (2025) https://doi.org/10.1016/j.coisb.2025.100556
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