Probing Control : Analysis and Design with Application to Fed-Batch Bioreactors

In most control problems the objective is to control the output at a desired value in spite of disturbances. In some cases, the best setpoint is not known a priori and it should be found online to optimize the process performance. This thesis examines a probing strategy that can be applied for this class of problems. The focus is on the application of the technique to the control of feed supply in fed-batch fermentations of the bacterium Escherichia coli. The thesis is divided into three parts. In the first part, the convergence properties of the probing algorithm are examined. The analysis is limited to processes modeled by a linear time-invariant dynamic in series with a static nonlinearity. Stability and performance analysis taking into account the process dynamic is performed. Tuning guidelines that help the user for the design are also derived. The second part presents a novel cultivation technique based on the probing approach. The fermentation technique combines the advantages of probing control and temperature-limited fed-batch technique. The feeding strategy is well adapted for prolonged operation at the maximum oxygen transfer capacity of the reactor. The efficiency of the method is demonstrated by simulations and experimental results. The strategy leads to a high biomass and it limits the degradation of the recombinant protein activity in the late production phase. In the third part, the probing feeding strategy is evaluated in industrial-scale bioreactors. Based on experimental results the influence of scale and complex medium is discussed. It is shown that the flexibility and robustness of the technique makes it a useful tool for process development

Oxygen Control for an Industrial Pilot-Scale Fed-Batch Filamentous Fungal Fermentation

Industrial filamentous fungal fermentations are typically operated in fed- batch mode. Oxygen control represents an important operational challenge due to the varying biomass concentration. In this study, oxygen control is implemented by manipulating the substrate feed rate, i.e. the rate of oxygen consumption. It turns out that the setpoint for dissolved oxygen represents a trade-off since a low dissolved oxygen value favors productivity but can also induce oxygen limitation. This paper addresses the regulation of dissolved oxygen using a cascade control scheme that incorporates auxiliary measurements to improve the control performance. The computation of an appropriate setpoint profile for dissolved oxygen is solved via process optimization. For that purpose, an existing morphologically structured model is extended to include the effects of both low levels of oxygen on growth and medium rheological properties on oxygen transfer. Experimental results obtained at the industrial pilot-scale level confirm the efficiency of the proposed control strategy but also illustrate the shortcomings of the process model at hand for optimizing the dissolved oxygen setpoints

Instrumentation and control of anaerobic digestion processes: a review and some research challenges

The final publication is available at Springer via http://dx.doi.org/10.1007/s11157-015-9382-6[EN] To enhance energy production from methane or resource recovery from digestate, anaerobic digestion processes require advanced instrumentation and control tools. Over the years, research on these topics has evolved and followed the main fields of application of anaerobic digestion processes: from municipal sewage sludge to liquid mainly industrial then municipal organic fraction of solid waste and agricultural residues. Time constants of the processes have also changed with respect to the treated waste from minutes or hours to weeks or months. Since fast closed loop control is needed for short time constant processes, human operator is now included in the loop when taking decisions to optimize anaerobic digestion plants dealing with complex solid waste over a long retention time. Control objectives have also moved from the regulation of key variables measured online to the prediction of overall process perfor- mance based on global off-line measurements to optimize the feeding of the processes. Additionally, the need for more accurate prediction of methane production and organic matter biodegradation has impacted the complexity of instrumentation and should include a more detailed characterization of the waste (e.g., biochemical fractions like proteins, lipids and carbohydrates)andtheirbioaccessibility andbiodegradability characteristics. However, even if in the literature several methodologies have been developed to determine biodegradability based on organic matter characterization, only a few papers deal with bioaccessibility assessment. In this review, we emphasize the high potential of some promising techniques, such as spectral analysis, and we discuss issues that could appear in the near future concerning control of AD processes.The authors acknowledge the financial support of INRA (the French National Institute for Agricultural Research), the French National Research Agency (ANR) for the "Phycover" project (project ANR-14-CE04-0011) and ADEME for Inter-laboratory assay financial support.Jimenez, J.; Latrille, E.; Harmand, J.; Robles Martínez, Á.; Ferrer Polo, J.; Gaida, D.; Wolf, C.... (2015). Instrumentation and control of anaerobic digestion processes: a review and some research challenges. Reviews in Environmental Science and Biotechnology. 14(4):615-648. doi:10.1007/s11157-015-9382-6S615648144Aceves-Lara CA, Latrille E, Steyer JP (2010) Optimal control of hydrogen production in a continuous anaerobic fermentation bioreactor. 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Process analytical technology in food biotechnology

Biotechnology is an area where precision and reproducibility are vital. This is due to the fact that products are often in form of food, pharmaceutical or cosmetic products and therefore very close to the human being. To avoid human error during the production or the evaluation of the quality of a product and to increase the optimal utilization of raw materials, a very high amount of automation is desired. Tools in the food and chemical industry that aim to reach this degree of higher automation are summarized in an initiative called Process Analytical Technology (PAT). Within the scope of the PAT, is to provide new measurement technologies for the purpose of closed loop control in biotechnological processes. These processes are the most demanding processes in regards of control issues due to their very often biological rate-determining component. Most important for an automation attempt is deep process knowledge, which can only be achieved via appropriate measurements. These measurements can either be carried out directly, measuring a crucial physical value, or if not accessible either due to the lack of technology or a complicated sample state, via a soft-sensor.Even after several years the ideal aim of the PAT initiative is not fully implemented in the industry and in many production processes. On the one hand a lot effort still needs to be put into the development of more general algorithms which are more easy to implement and especially more reliable. On the other hand, not all the available advances in this field are employed yet. The potential users seem to stick to approved methods and show certain reservations towards new technologies.Die Biotechnologie ist ein Wissenschaftsbereich, in dem hohe Genauigkeit und Wiederholbarkeit eine wichtige Rolle spielen. Dies ist der Tatsache geschuldet, dass die hergestellten Produkte sehr oft den Bereichen Nahrungsmitteln, Pharmazeutika oder Kosmetik angehöhren und daher besonders den Menschen beeinflussen. Um den menschlichen Fehler bei der Produktion zu vermeiden, die Qualität eines Produktes zu sichern und die optimale Verwertung der Rohmaterialen zu gewährleisten, wird ein besonders hohes Maß an Automation angestrebt. Die Werkzeuge, die in der Nahrungsmittel- und chemischen Industrie hierfür zum Einsatz kommen, werden in der Process Analytical Technology (PAT) Initiative zusammengefasst. Ziel der PAT ist die Entwicklung zuverlässiger neuer Methoden, um Prozesse zu beschreiben und eine automatische Regelungsstrategie zu realisieren. Biotechnologische Prozesse gehören hierbei zu den aufwändigsten Regelungsaufgaben, da in den meisten Fällen eine biologische Komponente der entscheidende Faktor ist. Entscheidend für eine erfolgreiche Regelungsstrategie ist ein hohes Maß an Prozessverständnis. Dieses kann entweder durch eine direkte Messung der entscheidenden physikalischen, chemischen oder biologischen Größen gewonnen werden oder durch einen SoftSensor. Zusammengefasst zeigt sich, dass das finale Ziel der PAT Initiative auch nach einigen Jahren des Propagierens weder komplett in der Industrie noch bei vielen Produktionsprozessen angekommen ist. Auf der einen Seite liegt dies mit Sicherheit an der Tatsache, dass noch viel Arbeit in die Generalisierung von Algorithmen gesteckt werden muss. Diese müsse einfacher zu implementieren und vor allem noch zuverlässiger in der Funktionsweise sein. Auf der anderen Seite wurden jedoch auch Algorithmen, Regelungsstrategien und eigne Ansätze für einen neuartigen Sensor sowie einen Soft-Sensors vorgestellt, die großes Potential zeigen. Nicht zuletzt müssen die möglichen Anwender neue Strategien einsetzen und Vorbehalte gegenüber unbekannten Technologien ablegen

Minimal time control of fed-batch bioreactor with product inhibition

International audienceThis paper is devoted to the minimal time control problem for fed-batch bioreactors, in presence of an inhibitory product, which is released by the biomass proportionally to its growth. We first consider a growth rate with substrate saturation and product inhibition, and we prove that the optimal strategy is fill and wait (bang-bang). We then investigate the case of the Jin growth rate which takes into account substrate and product inhibition. For this type of growth function, we can prove the existence of singular arc paths defining singular strategies. Several configurations are addressed depending on the parameter set. For each case, we provide an optimal feedback control of the problem (of type bang-bang or bang-singular-bang). These results are obtained gathering the initial system into a planar one by using conservation laws. Thanks to Pontryagin maximum principle, Green's theorem, and properties of the switching function, we obtain the optimal synthesis. A methodology is also proposed in order to implement the optimal feeding strategies

State estimation and trajectory tracking control for a nonlinear and multivariable bioethanol production system

In this paper a controller is proposed based on linear algebra for a fed-batch bioethanol production process. It involves fnding feed rate profles (control actions obtained as a solution of a linear equations system) in order to make the system follow predefned concentration profles. A neural network states estimation is designed in order to know those variables that cannot be measured. The controller is tuned using a Monte Carlo experiment for which a cost function that penalizes tracking errors is defned. Moreover, several tests (adding parametric uncertainty and perturbations in the control action) are carried out so as to evaluate the controller performance. A comparison with another controller is made. The demonstration of the error convergence, as well as the stability analysis of the neural network, are included.Fil: Fernández, Maria Cecilia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Ingeniería Química; ArgentinaFil: Pantano, Maria Nadia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rossomando, Francisco Guido. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Instituto de Automática. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Automática; ArgentinaFil: Ortiz, Oscar Alberto. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Ingeniería Química; ArgentinaFil: Scaglia, Gustavo Juan Eduardo. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Ingeniería Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Robust Nonlinear Model Predictive Control using Polynomial Chaos Expansions

The performance of model predictive controllers (MPCs) is largely dependent on the accuracy of the model predictions as compared to the actual plant outputs. Irrespective of the model used, first-principles (FP) or empirical, plant-model mismatch is unavoidable. Consequently, model based controllers must be robust to mismatch between the model predictions and the actual process behavior. Controllers that are not robust may result in poor closed loop response and even instability. Model uncertainty can generally be formulated into two broader forms, parametric uncertainty and unstructured uncertainty. Most of the current robust nonlinear MPC have been based on FP-model where only robustness to bounded disturbances rather than parametric uncertainty has been addressed. Systematically accounting for parametric uncertainty in the robust design has been difficult in FP-models due to varying forms in which uncertain parameters occur in the models. To address parametric uncertainty robustness tests based on Structured Singular Value (SSV) and Linear Matrix Inequalities (LMI) have been proposed previously, however these algorithms tend to be conservative because they consider worst-case scenarios and they are also computationally expensive. For instance the SSV calculation is NP-hard and as a result it is not suitable for fast computations. This provides motivation to work on robust control algorithms addressing both parametric and unstructured uncertainty with fast computation times. To facilitate the design of robust controllers which can be computed fast, empirical models are used in which parametric uncertainty is propagated using Polynomial Chaos Expansion (PCE) of parameters. PCE assists in speeding up the computations by providing an analytical expression for the L^2-norm of model predictions while also eliminating the need to design for the worst-case scenario which results in conservatism. Another way of speeding up computations in MPC algorithms is by grouping subsets of available the inputs and outputs into subsystems and by controlling each of the subsystems by MPC controllers of lower dimensions. This latter approach, referred in the literature as Distributed MPC, has been tackled by different strategies involving different degrees of coordination between subsystems but it has not been studied in terms of robustness to model error. Based on the above considerations the current work investigates different robustness aspects of predictive control algorithms for nonlinear processes with special emphasis on the following three situations, i) a nonlinear predictive control based on a Volterra series model where the uncertain parameters are formulated as PCE’s, ii) The application of a PCE-based approach to control and optimization of bioreactors where the model is based on dynamic flux metabolic models, and iii) A Robust Distributed MPC with a robust estimator that is needed to account for the interactions between sub-systems in distributed control

Modélisation et commande robuste des systèmes biologiques : exemple de la production d’acide lactique en fermenteur industriel

This PhD thesis focuses on the optimization of the bioprocess of lactic acid production from wheat flour. Indeed, lactic acid has received much attention for the production of PLA (Poly Lactic Acid), a biopolymer, since different inexpensive raw material such as wheat flour are now used as carbon source for its production. This work was performed in three main steps. In the first step, an innovative wheat transformation process is proposed, whose main steps are the following: a liquefaction followed by a simultaneous saccharification, proteins hydrolysis (SSPH) and and a final simultaneous saccharification, proteins hydrolysis and fermentation (SSPHF). Secondly, the modeling of the SSPHF (limiting step) in a continuous bioreactor is considered. The determination and validation of model parameters is performed by means of experimental campaigns in a 5 L bioreactor.In the last step, the development of control strategies to maintain the process at its optimal operating point is considered. To do so, due to the absence of sensors for real-time measurement of the concentrations of key variables of the bioreactor, estimators of these concentrations and of the lactic acid production rate are first developed. Then, control strategies for regulating the lactic acid concentration at its optimal value are designed and compared in simulation. An adaptive control combining a state feedback linearizing control and an estimator of the lactic acid production rate is finally chosen to be experimentally validated on an instrumented reactor. This strategy showed good robustness features with respect to modeling mismatches and was able during experiments to increase twice the lactic acid productivity.Cette thèse de doctorat porte sur l’optimisation du bioprocédé de production d’acide lactique à partir de la farine de blé. L'acide lactique s’avère en effet de plus en plus attractif pour la production de PLA (acide poly lactique), un bio polymère, d’autant plus que différentes matières premières peu coûteuses comme la farine de blé sont désormais utilisées comme sources de carbone pour sa production. Cette thèse comprend trois parties principales. Une première partie propose pour l’optimisation du procédé de transformation du blé un schéma innovant composé de trois étapes successives : une liquéfaction, suivi d’une étape de saccharification et hydrolyse des protéines simultanées (SSPH) et une étape finale de saccharification, hydrolyse des protéines et fermentation simultanées (SSPHF). La deuxième partie s’intéresse à la modélisation de l’étape SSPHF (étape limitante) dans un bioréacteur continu. La détermination des paramètres du modèle ainsi que leur validation sont réalisées à l’aide de campagnes d’essais sur un bioréacteur de 5 L.Enfin, la dernière partie développe la mise en oeuvre de stratégies de commande permettant de maintenir le bioprocédé à son point optimal de fonctionnement. Pour ce faire, du fait de l’absence de capteurs pour la mesure en temps réel des concentrations des variables clé dans le bioréacteur, des estimateurs de ces concentrations ainsi que du taux de production en acide lactique sont tout d’abord élaborés. Des stratégies de commande régulant la concentration d’acide lactique à sa valeur optimale sont ensuite synthétisées et comparées en simulation. Une commande adaptative combinant une commande linéarisante par retour d’état et un estimateur du taux de production en acide lactique est finalement retenue et validée expérimentalement sur un réacteur instrumenté. Cette dernière s’est avérée robuste vis-à-vis des erreurs de modélisation et a permis lors des expériences de doubler la productivité de l’acide lactique

Real-Time Substrate Feed Optimization of Anaerobic Co-Digestion Plants

In anaerobic co-digestion plants a mix of organic materials is converted to biogas using the anaerobic digestion process. These organic materials, called substrates, can be crops, sludge, manure, organic wastes and many more. They are fed on a daily basis and significantly affect the biogas production process. In this thesis dynamic real-time optimization of the substrate feed for anaerobic co-digestion plants is developed. In dynamic real-time optimization a dynamic simulation model is used to predict the future performance of the controlled plant. Therefore, a complex simulation model for biogas plants is developed, which uses the famous Anaerobic Digestion Model No. 1 (ADM1). With this model the future economics as well as stability can be calculated resulting in a multi-objective performance criterion. Using multi-objective nonlinear model predictive control (NMPC) the model predictions are used to find the optimal substrate feed for the biogas plant. Therefore, NMPC solves an optimization problem over a moving horizon and applies the optimal substrate feed to the plant for a short while before recalculating the new optimal solution. The multi-objective optimization problem is solved using state-of-the-art methods such as SMS-EMOA and SMS-EGO. The performance of the proposed approach is validated in a detailed simulation studyAlgorithms and the Foundations of Software technolog