Specific growth rate estimation in (fed-)batch bioreactors using second-order sliding observers

[EN] This paper addresses the estimation of specific growth rate of microorganisms in bioreactors using sliding observers. In particular, a second-order sliding observer based on biomass concentration measurement is proposed. Differing from other proposals that only guarantee bounded errors, the proposed observer provides a smooth estimate that converges in finite time to the time-varying parameter. Stability is proved using a Lyapunov approach. The observer exhibits also robustness to process uncertainties since no model of the reaction is used for its design. In addition, the off-surface coordinate of the sliding observer is useful to determine the convergence time as well as to identify sensor faults and unexpected behaviors. Because of the structure of the output error injection, chattering phenomena of conventional sliding mode algorithms are substantially reduced. The features of the proposed observer are assessed by numerical and experimental data. (C) 2011 Elsevier Ltd. All rights reserved.This work was supported by the National University of La Plata (Project 11-1127), ANPCyT (PICT2007-00535) and CONICET (PIP112-200801-01052) of Argentina; the Technical University of Valencia (PAID-02-09 program and FPI-2009/21 grant), the CICYT (DPI2005-01180) and AECID (A/024186/09) of Spain: and by FEDER funds of the European Union.De Battista, H.; Picó, J.; Garelli, F.; Vignoni, A. (2011). Specific growth rate estimation in (fed-)batch bioreactors using second-order sliding observers. Journal of Process Control. 21(7):1049-1055. https://doi.org/10.1016/j.jprocont.2011.05.008S1049105521

Enzymatic Synthesis of Ampicillin: Nonlinear Modeling, Kinetics Estimation, and Adaptive Control

Nowadays, the use of advanced control strategies in biotechnology is quite low. A main reason is the lack of quality of the data, and the fact that more sophisticated control strategies must be based on a model of the dynamics of bioprocesses. The nonlinearity of the bioprocesses and the absence of cheap and reliable instrumentation require an enhanced modeling effort and identification strategies for the kinetics. The present work approaches modeling and control strategies for the enzymatic synthesis of ampicillin that is carried out inside a fed-batch bioreactor. First, a nonlinear dynamical model of this bioprocess is obtained by using a novel modeling procedure for biotechnology: the bond graph methodology. Second, a high gain observer is designed for the estimation of the imprecisely known kinetics of the synthesis process. Third, by combining an exact linearizing control law with the on-line estimation kinetics algorithm, a nonlinear adaptive control law is designed. The case study discussed shows that a nonlinear feedback control strategy applied to the ampicillin synthesis bioprocess can cope with disturbances, noisy measurements, and parametric uncertainties. Numerical simulations performed with MATLAB environment are included in order to test the behavior and the performances of the proposed estimation and control strategies

Reaction rate reconstruction from biomass concentration measurement in bioreactors using modified second-order sliding mode algorithms

This paper deals with the estimation of unknown signals in bioreactors using sliding observers. Particular attention is drawn to estimate the specific growth rate of microorganisms from measurement of biomass concentration. In a recent article, notions of high-order sliding modes have been used to derive a growth rate observer for batch processes. In this paper we generalize and refine these preliminary results. We develop a new observer with a different error structure to cope with other types of processes. Furthermore, we show that these observers are equivalent, under coordinate transformations and time scaling, to the classical super-twisting differentiator algorithm, thus inheriting all its distinctive features. The new observers’ family achieves convergence to timevarying unknown signals in finite time, and presents the best attainable estimation error order in the presence of noise. In addition, the observers are robust to modeling and parameter uncertainties since they are based on minimal assumptions on bioprocess dynamics. In addition, they have interesting applications in fault detection and monitoring. The observers performance in batch, fed-batch and continuous bioreactors is assessed by experimental data obtained from the fermentation of Saccharomyces Cerevisiae on glucose.This work was supported by the National University of La Plata (Project 2012-2015), the Agency for the Promotion of Science and Technology ANPCyT (PICT2007-00535) and the National Research Council CONICET (PIP112-200801-01052) of Argentina; the Technical University of Valencia (PAID-02-09), the CICYT (DPI2005-01180) and AECID (A/024186/09) of Spain; and by the project FEDER of the European Union.De Battista, H.; Picó Marco, JA.; Garelli, F.; Navarro Herrero, JL. (2012). Reaction rate reconstruction from biomass concentration measurement in bioreactors using modified second-order sliding mode algorithms. Bioprocess and Biosystems Engineering. 35(9):1-11. https://doi.org/10.1007/s00449-012-0752-yS111359Aborhey S, Williamson D (1978) State amd parameter estimation of microbial growth process. Automatica 14:493–498Bastin G, Dochain D (1986) On-line estimation of microbial specific growth rates. Automatica 22:705–709Bastin G, Dochain D (1990) On-line estimation and adaptive control of bioreactors. Elsevier, AmsterdamBejarano F, Fridman L (2009) Unbounded unknown inputs estimation based on high-order sliding mode differentiator. In: Proceedings of the 48th IEEE conference on decision and control, pp 8393–8398Corless M, Tu J (1998) State and input estimation for a class of uncertain systems. Automatica 34(6):757–764Dabros M, Schler M, Marison I (2010) Simple control of specific growth rate in biotechnological fed-batch processes based on enhanced online measurements of biomass. Bioprocess Biosyst Eng 33:1109–1118Davila A, Moreno J, Fridman L (2010) Variable gains super-twisting algorithm: a lyapunov based design. In: American control conference (ACC), 2010, pp 968–973Dávila J, Fridman L, Levant A (2005) Second-order sliding-mode observer for mechanical systems. IEEE Transact Automatic Control 50(11):1785–1789De Battista H, Picó J, Garelli F, Vignoni A (2011) Specific growth rate estimation in (fed-)batch bioreactors using second-order sliding observers. J Process Control 21:1049–1055Dochain D (2001) Bioprocess control. Wiley, HobokenDochain D (2003) State and parameter estimation in chemical and biochemical processes: a tutorial. J Process Control 13(8):801–818Edwards C, Spurgeon S, Patton R (2000) Sliding mode observers for fault detection and isolation. Automatica 36(2):541–553Evangelista C, Puleston P, Valenciaga F, Fridman L (2012) Lyapunov designed super-twisting sliding mode control for wind energy conversion optimization. Indus Electron IEEE Transact. doi: 10.1109/TIE.2012.2188256Farza M, Busawon K, Hammouri H (1998) Simple nonlinear observers for on-line estimation of kinetic rates in bioreactors. Automatica 34(3):301–318Fridman L, Davila J, Levant A (2008) High-order sliding modes observation. In: International workshop on variable structure systems, pp 203–208Fridman L, Levant A (2002) Sliding mode control in engineering, higher-order sliding modes. Marcel Dekker, Inc., New York, pp 53–101Fridman L, Shtessel Y, Edwards C, Yan X (2008) Higher-order sliding-mode observer for state estimation and input reconstruction in nonlinear systems. Int J Robust Nonlinear Control 18(3–4):399–412Gauthier J, Hammouri H, Othman S (1992) A simple observer for nonlinear systems: applications to bioreactors. IEEE Transact Automatic Control 37(6):875–880Gnoth S, Jenzsch M, Simutis R, Lubbert A (2008) Control of cultivation processes for recombinant protein production: a review. Bioprocess Biosyst Eng 31(1):21–39Hitzmann B, Broxtermann O, Cha Y, Sobieh O, Stärk E, Scheper T (2000) The control of glucose concentration during yeast fed-batch cultivation using a fast measurement complemented by an extended kalman filter. Bioprocess Eng 23(4):337–341Kiviharju K, Salonen K, Moilanen U, Eerikainen T (2008) Biomass measurement online: the performance of in situ measurements and software sensors. J Indus Microbiol Biotechnol 35(7):657–665Levant A (1998) Robust exact differentiation via sliding mode technique. Automatica 34(3):379–384Levant A (2003) Higher-order sliding modes, differentiation and output-feedback control. Int J Control 76(9/10):924–941Lubenova V, Rocha I, Ferreira E (2003) Estimation of multiple biomass growth rates and biomass concentration in a class of bioprocesses. Bioprocess Biosyst Eng 25:395–406Moreno J, Alvarez J, Rocha-Cozatl E, Diaz-Salgado J (2010) Super-twisting observer-based output feedback control of a class of continuous exothermic chemical reactors. In: Proceedings of the 9th IFAC international symposium on dynamics and control of process systems, pp 719–724. Leuven, BelgiumMoreno J, Osorio M (2008) A Lyapunov approach to second-order sliding mode controllers and observers. In: Proceedings of the 47th IEEE conference on decision and control. Cancún, México, pp 2856–2861Moreno J, Osorio M (2012) Strict Lyapunov functions for the super-twisting algorithm. IEEE Transact Automatic Control 57:1035–1040Navarro J, Picó J, Bruno J, Picó-Marco E, Vallés S (2001) On-line method and equipment for detecting, determining the evolution and quantifying a microbial biomass and other substances that absorb light along the spectrum during the development of biotechnological processes. Patent ES20010001757, EP20020751179Neeleman Boxtel (2001) Estimation of specific growth rate from cell density measurements. Bioprocess Biosyst Eng 24(3):179–185November E, van Impe J (2002) The tuning of a model-based estimator for the specific growth rate of Candidautilis. Bioprocess Biosyst Eng 25:1–12Park Y, Stein J (1988) Closed-loop, state and input observer for systems with unknown inputs. Int J Control 48(3):1121–1136Perrier M, de Azevedo SF, Ferreira E, Dochain D (2000) Tuning of observer-based estimators: theory and application to the on-line estimation of kinetic parameters. Control Eng Pract 8:377–388Picó J, De Battista H, Garelli F (2009) Smooth sliding-mode observers for specific growth rate and substrate from biomass measurement. J Process Control 19(8):1314–1323. 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Fermentation: Metabolism, Kinetic Models, and Bioprocessing

Biochemical and metabolic interpretation of microbial growth is an important topic in bioreactor design. We intend to address valuable information about the relation of critical operation variables and the simulation of bioprocesses with unstructured and structured kinetic models. Process parameters such as nutrient supply, pH, dissolved oxygen, and metabolic end-products directly impact the physiology and metabolism of microorganisms. Changes in the membrane as well as cell viability are of interest since protein expression and maturation in prokaryota are directly related to membrane integrity. This chapter intends to deliver an insight of different alternatives in kinetic modeling

Nonlinear model of leachate anaerobic digestion treatment process

In this report a continuous adaptive high-gain observer method is presented for the estimation of state variables that could not be measurable online and unknown time-varying parameters of leachate anaerobic digestion treatment process. The high-gain observer is a variant of the Luenberger extended observer and involves an adjustable gain parameter. It is characterized by easy implementation and calibration, is stable and exhibit exponential convergence. The observer is based on a simplified mathematical model of the system. Calibration of the model was performed with real data from the Upflow Anaerobic Sludge Blanket (UASB) reactor for landfill leachate treatment in open loop under normal operational conditions. The model performance is evaluated via numerical simulations showing adequate results. The criteria used for considering the model as acceptable is to calculate the values of Mean Magnitude of Relative Error (MMRE) and Prediction at level l.Preprin

Development of software sensors for on-line monitoring of bakers yeast fermentation process

Software sensors and bioprocess are well-established research areas which have much to offer each other. Under the perspective of the software sensors area, bioprocess can be considered as a broad application area with a growing number of complex and challenging tasks to be dealt with, whose solutions can contribute to achieving high productivity and high-quality products. Although throughout the past years in the field of software sensors and bioprocess, progress has been quick and with a high degree of success, there is still a lack of inexpensive and reliable sensors for on-line state and parameter estimation. Therefore, the primary objective of this research was to design an inexpensive measurement system for on-line monitoring of ethanol production during the backers yeast cultivation process. The measurement system is based on commercially available metal oxide semiconductor gas sensors. From the bioreactor headspace, samples are pumped past the gas sensors array for 10 s every five minutes and the voltage changes of the sensors are measured. The signals from the gas sensor array showed a high correlation with ethanol concentration during cultivation process. In order to predict ethanol concentrations from the data of the gas sensor array, a principal component regression (PCR) model was developed. For the calibration procedure no off-line sampling was used. Instead, a theoretical model of the process is applied to simulate the ethanol production at any given time. The simulated ethanol concentrations were used as reference data for calibrating the response of the gas sensor array. The obtained results indicate that the model-based calibrated gas sensor array is able to predict ethanol concentrations during the cultivation process with a high accuracy (root mean square error of calibration as well as the percentage error for the validation sets were below 0.2 gL-1 and 7 %, respectively). However the predicted values are only available every five minutes. Therefore, the following plan of the research goal was to implement an estimation method for continues prediction of ethanol as well as glucose, biomass and the growth rates. For this reason, two nonlinear extensions of the Kalman filter namely the extended Kalman filter (EKF) and the unscented Kalman filter (UKF) were implemented separately for state and parameter estimation. Both prediction methods were validated on three different cultivation with variability of the substrate concentrations. The obtained results showed that both estimation algorithms show satisfactory results with respect to estimation of concentrations of substrates 6 and biomass as well as the growth rate parameters during the cultivation. However, despite the easier implementation producer of the UKF, this method shows more accurate prediction results compared to the EKF prediction method. Another focus of this study was to design and implement an on-line monitoring and control system for the volume evaluation of dough pieces during the proofing process of bread making. For this reason, a software sensor based on image processing was designed and implemented for measuring the dough volume. The control system consists of a fuzzy logic controller which takes into account the estimated volume. The controller is designed to maintain the volume of the dough pieces similar to the volume expansion of a dough piece in standard conditions during the proofing process by manipulating the temperature of the proofing chamber. Dough pieces with different amounts of backers yeast added in the ingredients and in different temperature starting states were prepared and proofed with the supervision of the software sensor and the fuzzy controller. The controller was evaluated by means of performance criteria and the final volume of the dough samples. The obtained results indicate that the performance of the system is very satisfactory with respect to volume control and set point deviation of the dough pieces.Softwaresensoren und Bioprozese sind gut etablierte Forschungsgebiete, die sich gegenseitig viel befruchten können. Unter dem Blickwinkel der Softwaresensorik kann der Bioprozess als ein breites Anwendungsgebiet mit einer wachsenden Zahl komplexer und anspruchsvoller Aufgabenstellungen betrachtet werden, deren Lösung zur Erzielung hoher Produktivität und qualitativ hochwertiger Produkte beitragen kann. Obwohl in den letzten Jahren auf dem Gebiet der Softwaresensoren und des Bioprozesses rasch und mit großem Erfolg Untersuchung erzielt wurden, fehlt es immer noch an kostengünstigen und zuverlässigen Sensoren für die Online-Zustands- und Parameterschätzung. Daher war das primäre Ziel dieser Forschung die Entwicklung eines kostengünstigen Messsystems für die Online-Überwachung der Ethanolproduktion während des Kultivierungsprozesses von Backhefe. Das Messsystem basiert auf kommerziell erhältlichen Metalloxid-Halbleiter-Gassensoren. Die Headspace-Proben des Bioreaktors werden alle fünf Minuten für 10 s an der Gassensor-Anordnung vorbeigepumpt und die Spannungsänderungen der Sensoren werden gemessen. Die Signale des Gassensorarrays zeigten eine hohe Korrelation mit der Ethanolkonzentration während des Kultivierungsprozesses. Um die Ethanolkonzentrationen aus den Daten des Gassensorarrays vorherzusagen, wurde ein Hauptkomponenten-Regressionsmodell (PCR) verwendet. Für das Kalibrierungsverfahren ist keine Offline-Probenahme notwendig. Stattdessen wird ein theoretisches Modell des Prozesses genutzt, um die Ethanolproduktion zu jedem beliebigen Zeitpunkt zu simulieren. Die kinetischen Parameter des Modells werden im Rahmen der Kalibration bestimmt. Die simulierten Ethanolkonzentrationen wurden als Referenzdaten für die Kalibrierung des Ansprechverhaltens des Gassensorarrays verwendet. Die erhaltenen Ergebnisse zeigen, dass das modellbasierte kalibrierte Gassensorarray in der Lage ist, die Ethanolkonzentrationen während des Kultivierungsprozesses mit hoher Genauigkeit vorherzusagen (der mittlere quadratische Fehler der Kalibrierung sowie der prozentuale Fehler für die Validierungssätze lagen unter 0,2 gL-1 bzw. 7 %). Die vorhergesagten Werte sind jedoch nur alle fünf Minuten verfügbar. Daher war der folgende Plan der Untersuchung die Implementierung einer Schätzmethode zur kontinuierlichen Vorhersage von Ethanol sowie von Glukose, Biomasse und der Wachstumsrate. Aus diesem Grund wurden zwei nichtlineare Erweiterungen des Kalman Filters, nämlich der erweiterte Kalman Filter (EKF) und der unscented Kalman Filter (UKF), getrennt für die Zustands und Parameterschätzung implementiert. Beide 8 Vorhersagemethoden wurden an drei verschiedenen Kultivierungen mit Variabilität der Start substratkonzentrationen validiert. Die erhaltenen Ergebnisse zeigen, dass beide Schätzungsalgorithmen zufriedenstellende Ergebnisse hinsichtlich der Schätzung der Konzentrationen von Substraten und Biomasse sowie der Parameter der Wachstumsrate während der Kultivierung ermitteln. Trotz der einfacheren Implementierung des UKF zeigt diese Methode jedoch genauere Vorhersageergebnisse im Vergleich zur EKF-Vorhersagemethode. Ein weiterer Schwerpunkt dieser Untersuchung war der Entwurf und die Implementierung eines Online-Überwachungs- und Regelungssystems für die Volumenauswertung von Teigstücken während des Gärprozesses bei der Brotherstellung. Aus diesem Grund wurde ein auf Bildverarbeitung basierendes Überwachungssystem zur Messung der Teigvolumenauswertung entworfen und implementiert. Das Regelsystem besteht aus einem Fuzzy-Logic-Controller, der das gemessene Volumen für die Regelung nutzt. Die Regelung ist so ausgelegt, dass das Volumen der Teiglinge mit Werten des Volumens eines Teiglings unter Standardbedingungen während des Gärprozesses vergleicht und die Temperatur der Gärkammer entsprechend anpasst. Teiglinge mit unterschiedlichen Hefemengen in den Zutaten und verschiedenen Temperaturstartwerten wurden vorbereitet und unter Anwendung des Fuzzy-Reglers gegärt. Der Regler wurde anhand von Leistungskriterien und dem Endvolumen der Teigproben bewertet. Die erhaltenen Ergebnisse zeigen, dass die Leistung des Systems in Bezug auf die Volumenregelung und die Sollwertabweichung der Teigstücke sehr zufriedenstellend ist

Nonlinear model of leachate anaerobic digestion treatment process

In this report a continuous adaptive high−gain observer method is presented for the estimation of state variables that could not be measurable online and unknown time−varying parameters of leachate anaerobic digestion treatment process. The high−gain observer is a variant of the Luenberger extended observer and involves an adjustable gain parameter. It is characterized by easy implementation and calibration, is stable and exhibit exponential convergence. The observer is based on a simplified mathematical model of the system. Calibration of the model was performed with real data from the Upflow Anaerobic Sludge Blanket (UASB) reactor for landfill leachate treatment in open loop under normal operational conditions. The model performance is evaluated via numerical simulations showing adequate results. The criteria used for considering the model as acceptable is to calculate the values of Mean Magnitude of Relative Error (MMRE) and Prediction at level l.Peer reviewe

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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Global stabilisation of continuous bioreactors: tools for analysis and design of feeding laws

[EN] This work revisits the dynamic behaviour of stirred continuous reactors in which a single bioreaction with unknown kinetics occurs. Conditions on the feeding strategy to avoid washing out the biomass and falling in batch operation are obtained. These conditions derive in a closed positively invariant region including the desired operating point. It is stated that no closed orbits may exist in this region and, furthermore, that no fixed point exists but on one of its borders. Therefore, global stability is achieved by finding a feeding law that fulfils the aforementioned invariant conditions and gives a single equilibrium for a first-order dynamics. These results are useful to determine the stability properties of different control laws and, more importantly, to design new ones. The main advantages of the proposed approach are its simplicity and that, differing from previous results, input saturation does not affect stability results. The potentiality of the developed tools is illustrated by means of classical and novel feeding laws. (C) 2017 Elsevier Ltd. All rights reserved.Financed by I216-2016 (UNLP), PICT2014-2394 (ANPCyT) and PIP112-2015-01-00837 (CONICET), Argentina; and by DPI2014-55276-C5-1-R MINECO/AEI/FEDER, UE. The material in this paper was not presented at any conference.De Battista, H.; Jamilis, M.; Garelli, F.; Picó, J. (2018). Global stabilisation of continuous bioreactors: tools for analysis and design of feeding laws. Automatica. 89:340-348. https://doi.org/10.1016/j.automatica.2017.12.041S3403488