Papers by Laurent Dewasme
This study aims at providing a methodology based on both data- and knowledge-driven approaches to... more This study aims at providing a methodology based on both data- and knowledge-driven approaches to build dynamic macroscopic models of cell cultures. This methodology proceeds in three steps. A principal component analysis is first applied in order to determine the minimum number of macroreactions necessary to faithfully describe the available data. These reactions are then selected among the elementary flux modes associated with a chosen metabolic network through the definition of an original linear programming problem. Kinetic laws are finally identified so as to reproduce the measurement data. The proposed methodology is illustrated using four different perfusion cultures of hybridoma cells and demonstrates a good capacity to select macroreactions capable of reproducing well the complex experimental data, even with the use of simple kinetic laws and without re-identifying the stoichiometry.
Nonlinear model predictive control of Escherichia coli culture
Nonlinear model predictive control of a twin-screw extruder
In the field of industrial product manufacturing processes, hot-melt extrusion becomes more and m... more In the field of industrial product manufacturing processes, hot-melt extrusion becomes more and more popular. In this context, a distributed parameter model consisting in partial differential equations derived from mass and energy balances is applied to a specific device with a complex screw geometry. Several numerical simulations bring out strong nonlinearities and input-output coupling. Following these observations, a nonlinear model predictive control (NMPC) strategy is proposed and designed to regulate the output API concentration and the output flow. Numerical validations and robustness analysis with respect to measurement and model noises are achieved to show the effectiveness of the strategy.
This paper is dedicated to the experimental validation of a cascade control strategy for simultan... more 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 satisfacto...
Fast transient optimization of social distancing during Covid-19 pandemics using extremum seeking
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Processes
This work proposes a Generic Model Control (GMC) strategy to regulate biomass growth in fed-batch... more This work proposes a Generic Model Control (GMC) strategy to regulate biomass growth in fed-batch cultures of Escherichia coli BL21(DE3). The control law is established using a previously validated mechanistic model based on the overflow metabolism paradigm. A model reduction is carried out to prevent the controller from relying on kinetics, which may be uncertain. In order to limit the controller to the use of a single measurement, i.e., biomass concentration which is readily available, a Kalman filter is designed to reconstruct the nonmeasurable information from the outlet gas and the remaining stoichiometry. Several numerical simulations are presented to assess the controller robustness with respect to model uncertainty. Experimental validation of the proposed GMC strategy is achieved with a lab-scale bioreactor.
An experimental assessment of robust control and estimation of acetate concentration in Escherichia coli BL21(DE3) fed-batch cultures
Biochemical Engineering Journal
Microorganisms
Rhodospirillum rubrum has a versatile metabolism, and as such can assimilate a broad range of car... more Rhodospirillum rubrum has a versatile metabolism, and as such can assimilate a broad range of carbon sources, including volatile fatty acids. These carbon sources are gaining increasing interest for biotechnological processes, since they reduce the production costs for numerous value-added compounds and contribute to the development of a more circular economy. Usually, studies characterizing carbon metabolism are performed by supplying a single carbon source; however, in both environmental and engineered conditions, cells would rather grow on mixtures of volatile fatty acids (VFAs) generated via anaerobic fermentation. In this study, we show that the use of a mixture of VFAs as carbon source appears to have a synergy effect on growth phenotype. In addition, while propionate and butyrate assimilation in Rs. rubrum is known to require an excess of bicarbonate in the culture medium, mixing them reduces the requirement for bicarbonate supplementation. The fixation of CO2 is one of the m...
Maximum-likelihood extremum seeking control of microalgae cultures
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Water Science and Technology
This work focused on the experimental validation of software sensors with a view to improving on-... more This work focused on the experimental validation of software sensors with a view to improving on-line anaerobic digester monitoring. Based on cheaply available measurements such as conductivity, temperature, pH, redox potential, total suspended solids concentration and digester inflows and outflows, an intelligent estimator was built to reproduce the evolutions of key components such as volatile fatty acid, carbonate and alkalinity concentrations, as well as biogas composition (methane and carbon dioxide). The proposed solution considers a principal component pre-processing of the data selected as inputs of a radial basis function neural network (RBF-ANN) structure, using a particular sequential learning algorithm. Process dynamics were also taken into account, introducing a moving horizon version of this network (MH-RBF-ANN). Experimental results demonstrated the capacity of the MH-RBF-ANN to correctly predict the key-component evolutions and to improve the estimation accuracy, com...
Modelling a hyper-proliferative E. coli
Processes
Uncertainty is a common feature of biological systems, and model-free extremum-seeking control ha... more Uncertainty is a common feature of biological systems, and model-free extremum-seeking control has proved a relevant approach to avoid the typical problems related to model-based optimization, e.g., time- and resource-consuming derivation and identification of dynamic models, and lack of robustness of optimal control. In this article, a review of the past and current trends in model-free extremum seeking is proposed with an emphasis on finding optimal operating conditions of bioprocesses. This review is illustrated with a simple simulation case study which allows a comparative evaluation of a few selected methods. Finally, some experimental case studies are discussed. As usual, practice lags behind theory, but recent developments confirm the applicability of the approach at the laboratory scale and are encouraging a transfer to industrial scale.
An experimental application of extremum seeking control to cultures of the microalgae Scenedesmus obliquus in a continuous photobioreactor
International Journal of Adaptive Control and Signal Processing
Processes
The recirculating aquaculture system (RAS) is a land-based water treatment technology, which allo... more The recirculating aquaculture system (RAS) is a land-based water treatment technology, which allows for farming aquatic organisms, such as fish, by reusing the water in the production (often less than 5%). This technology is based on the use of filters, either mechanical or biological, and can, in principle, be used for any species grown in aquaculture. Due to the low recirculation rate, ammonia accumulates in the system and must be converted into nitrate using nitrification reactors. Although less toxic for fish, nitrate can also be further reduced into nitrogen gas by the use of denitrification biofilters which may create several issues, such as incomplete denitrification, resulting in toxic substances, such as nitrite and nitric oxide, or a waste of carbon source in excess. Control of the added quantity of carbon source in the denitrification biofilter is then mandatory to keep nitrate/nitrite concentrations under toxic levels for fish and in accordance with local effluent regula...
Processes
This paper is dedicated to the experimental validation of a cascade control strategy for simultan... more 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 satisfacto...
IFAC-PapersOnLine
This paper presents experimental results of a lab-scale implementation of an extremum seeking con... more This paper presents experimental results of a lab-scale implementation of an extremum seeking control strategy for maximizing the biomass productivity of cultures of the micro-algae Dunaliella tertiolecta in a flat-panel photobioreactor operated in continuous mode. The real-time optimization is based on a recursive least squares adaptation where the input (Dilution rate)/output (Biomass concentration) relation is approximated by a linear Hammerstein regression from which a productivity gradient estimate can be inferred. Lab-scale instrumentation and operating conditions are described and the results of two experiments are presented. They demonstrate the fast convergence of the extremum seeking scheme and practical considerations related to stability are discussed.
Adaptive Flux Variability Analysis of HEK Cell Cultures
Computers & Chemical Engineering
Bioprocess and Biosystems Engineering
Starting from a relatively detailed model of a bioprocess producing fructo-oligosaccharides, a se... more Starting from a relatively detailed model of a bioprocess producing fructo-oligosaccharides, a set of experimental data collected in batch and fed-batch experiments is exploited to estimate the unknown model parameters. The original model includes the growth of the fungus Aureobasidium pullulans which produces the enzymes responsible for the hydrolysis and transfructosylation reactions, and as such contains 25 kinetic parameters and 16 pseudo-stoichiometric coefficients, which are not uniquely identifiable with the data at hand. The aim of this study is, therefore, to show how sensitivity analysis and quantitative indicators based on the Fisher information matrix can be used to reduce the detailed model to a practically identifiable model. Parametric sensitivity analysis can indeed be used to progressively simplify the model to a representation involving 15 kinetic parameters and 8 pseudo-stoichiometric coefficients. The reduced model provides satisfactory prediction and can be convincingly cross validated. Keywords Mathematical modeling • Fisher information matrix • Parameter identification • Biotechnology List of symbols GF Sucrose concentration (g L −1) GF 2 1-Kestose concentration (g L −1) GF 3 Nystose concentration (g L −1) GF 4 Fructofuranosylnystose concentration (g L −1) F Fructose concentration (g L −1) G Glucose concentration (g L −1) X Biomass concentration (g L −1) r i , i = 1, … , 4 Hydrolysis reaction rates (g L −1 h −1) r i , i = 5, 6, 7 Transfructosylation reaction rates (g L −1 h −1) r i , i = 8, 9 Biomass production reaction rates (g L −1 h −1) k i , i = 1, … , 14 Pseudo-stoichiometric coefficients Y F Biomass yield coefficient from fructose Y G Biomass yield coefficient from glucose Vmh GF Maximum hydrolysis rate for sucrose (g L −1 h −1) Kmh GF Michaelis-Menten constant for sucrose (g L −1) Vmh GF i Maximum hydrolysis rate for GF i (g L −1 h −1) Kmh GF i Michaelis-Menten constant for GF i (g L −1) Kih GF i Substrate inhibition constant for GF i (g L −1) VmT GF Maximum transfructosylation rate for sucrose (g L −1 h −1) Kmst Michaelis-Menten constant for sucrose (g L −1) Ksts Substrate inhibition constant for sucrose (g L −1) Kgst Competitive inhibition constant for glucose VmT GF i Maximum transfructosylation rate for GF i (g L −1 h −1) Kmt GF i Michaelis-Menten constant for GF i (g L −1) Kit GF i Competitive inhibition constant for GF i
A slope seeking-based approach for optimal and sub-optimal SISO process control: Application to microalgae culture
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Extremum seeking based on a Hammerstein-Wiener representation
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Papers by Laurent Dewasme