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Updated: Feb 22, 2026

Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation
Published on: May 18, 2020
Hybrid Approach to State Estimation for Bioprocess Control
Rimvydas Simutis1, Andreas Lübbert2
1Department of Automation, Kaunas University of Technology, Kaunas 44249, Lithuania. Rimvydas.simutis@ktu.lt.
Abstract:
An improved state estimation technique for bioprocess control applications is proposed where a hybrid version of the Unscented Kalman Filter (UKF) is employed. The underlying dynamic system model is formulated as a conventional system of ordinary differential equations based on the mass balances of the state variables biomass, substrate, and product, while the observation model, describing the less established relationship between the state variables and the measurement quantities, is formulated in a data driven way. The latter is formulated by means of a support vector regression (SVR) model. The UKF is applied to a recombinant therapeutic protein production process using Escherichia coli bacteria. Additionally, the state vector was extended by the specific biomass growth rate µ in order to allow for the estimation of this key variable which is crucial for the implementation of innovative control algorithms in recombinant therapeutic protein production processes. The state estimates depict a sufficiently low noise level which goes perfectly with different advanced bioprocess control applications.
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