A simple output-feedback strategy for the control of perfused mammalian cell cultures

Sbarciog, Mihaela; Coutinho, Daniel; Wouwer, Alain Vande

doi:10.1016/j.conengprac.2014.08.002

Cited by 12 publications

(9 citation statements)

References 24 publications

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“…The distinctive feature of our control strategy [19] is to allow controlling independently biomass and glucose at specific setpoints during the course of the culture, the underlying idea being that cell density is related to the productivity objective, whereas glucose concentration is linked to the consumption of the culture medium. The latter could be a secondary objective, i.e., to achieve the targeted production while minimizing in some sense the waste of unused nutrients in the culture medium.…”

Section: Cascade Control Strategymentioning

confidence: 99%

“…With these challenges in view, we proposed in [19] an original cascade control structure to regulate biomass and glucose concentrations at the desired levels. The motivation behind this structure is that biomass is a key indicator of the bioproduction, while glucose is a key indicator of the actual consumption of the culture medium.…”

Section: Introductionmentioning

confidence: 99%

“…The proposed cascade strategy was extensively tested in simulation in [19] using a nonlinear dynamic model to emulate the reality. The next logical step is the implementation of the strategy in a real-life bioprocess, and it is precisely the purpose of this article to report on the experimental validation of the former promising results on a lab-scale bioreactor.…”

Section: Introductionmentioning

confidence: 99%

“…The paper is organized as follows. The next section presents the principles of the original algorithm developed in [19] and introduces the improvements that are brought to the algorithm. Section 3 presents a model used in simulation to compare the efficiency of both the control versions and to set up the different parameters of the controllers.…”

Section: Introductionmentioning

confidence: 99%

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Experimental Validation of a Cascade Control Strategy for Continuously Perfused Animal Cell Cultures

et al. 2020

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This paper is dedicated to the experimental validation of a cascade control strategy for simultaneously regulating the glucose and biomass levels in continuously perfused HEK-293 cell cultures. The inner loop consists of a partial feedback linearization, which requires the estimation of the biomass specific growth rate and glucose uptake rate. This latter task is achieved by sliding mode observers, which do not require a priori process knowledge in the form of a process model. The linearized process is then regulated by the outer loop, including two classical PI controllers with autotuning. The four manipulated variables are a feed flow rate with low glucose concentration, another feed flow with a higher glucose content, a bleed flow, and a perfusion stream. The experimental results demonstrate the ability of the control strategy to reach and regulate the prescribed setpoints. The main advantage of the strategy is that it can be applied in a plug and play manner and shows satisfactory robustness. To the best of our knowledge, this is the first time that such a multivariable control strategy, together with sliding mode observers, is applied at the lab scale to an industrial process in the pharmaceutical sector.

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Section: Cascade Control Strategymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Experimental Validation of a Cascade Control Strategy for Continuously Perfused Animal Cell Cultures

et al. 2020

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“…Assuming spatial homogeneity and neglecting the effects of physical environmental parameters have been the basis of most culture models [19][20][21][22][23][24][25][26][27][28][29]. This reduces the problem of simulating relevant portions of cellular activities that control the production of a product of interest.…”

Section: Existing Culture Models and Their Need For Improvementmentioning

confidence: 99%

A Framework for the Development of Integrated and Computationally Feasible Models of Large-Scale Mammalian Cell Bioreactors

Farzan

Ierapetritou

2018

Processes

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Industrialization of bioreactors has been achieved by applying several core concepts of science and engineering. Modeling has deepened the understanding of biological and physical phenomena. In this paper, the state of existing cell culture models is summarized. A framework for development of dynamic and computationally feasible models that capture the interactions of hydrodynamics and cellular activities is proposed. Operating conditions are described by impeller rotation speed, gas sparging flowrate, and liquid fill level. A set of admissible operating states is defined over discretized process parameters. The burden on a dynamic solver is reduced by assuming hydrodynamics at its fully developed state and implementation of compartmental modeling. A change in the conditions of operation is followed by hydrodynamics switching instantaneously to the steady state that would be reached under new conditions. Finally, coupling the model with optimization solvers leads to improvements in operation.

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Review of the important challenges and opportunities related to modeling of mammalian cell bioreactors

2016

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Industrialization of mammalian cell culture has been achieved by integrating knowledge from several applying core concepts of chemical engineering, cellular and molecular biology, and biochemistry. Modeling has been applied to biological and physical processes to gain additional insights into such processes. This article covers modeling of the bioreactor and metabolic processes as it applies to bioprocess. Hydrodynamics of a bioreactor is briefly described while additional focus is given to gas‐liquid mass transfer. Biological modeling is presented in the order of increasing complexity. First steady state models are presented followed by dynamic models, cybernetic models, and finally bioreactor integrated models. The closing discussion summarizes challenges of implementation of model‐based approaches in the biopharmaceutical industry. © 2016 American Institute of Chemical Engineers AIChE J, 63: 398–408, 2017

show abstract

A simple output-feedback strategy for the control of perfused mammalian cell cultures

Cited by 12 publications

References 24 publications

Experimental Validation of a Cascade Control Strategy for Continuously Perfused Animal Cell Cultures

Experimental Validation of a Cascade Control Strategy for Continuously Perfused Animal Cell Cultures

A Framework for the Development of Integrated and Computationally Feasible Models of Large-Scale Mammalian Cell Bioreactors

Review of the important challenges and opportunities related to modeling of mammalian cell bioreactors

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