Optimization of fed-batch fermentation processes using the Backtracking Search Algorithm

Fed-batch fermentation has gained attention in recent years due to its beneficial impact in the economy and productivity of bioprocesses. However, the complexity of these processes requires an expert system that involves swarm intelligence-based metaheuristics such as Artificial Algae Algorithm (AAA), Artificial Bee Colony (ABC), Covariance Matrix Adaptation Evolution Strategy (CMAES) and Differential Evolution (DE) for simulation and optimization of the feeding trajectories. DE traditionally performs better than other evolutionary algorithms and swarm intelligence techniques in optimization of fed-batch fermentation. In this work, an improved version of DE namely Backtracking Search Algorithm (BSA) has edged DE and other recent metaheuristics to emerge as superior optimization method. This is shown by the results obtained by comparing the performance of BSA, DE, CMAES, AAA and ABC in solving six fed batch fermentation case studies. BSA gave the best overall performance by showing improved solutions and more robust convergence in comparison with various metaheuristics used in this work. Also, there is a gap in the study of fed-batch application of wastewater and sewage sludge treatment. Thus, the fed batch fermentation problems in winery wastewater treatment and biogas generation from sewage sludge are investigated and reformulated for optimization

Continuous Biochemical Processing: Investigating Novel Strategies to Produce Sustainable Fuels and Pharmaceuticals

Biochemical processing methods have been targeted as one of the potential renewable strategies for producing commodities currently dominated by the petrochemical industry. To design biochemical systems with the ability to compete with petrochemical facilities, inroads are needed to transition from traditional batch methods to continuous methods. Recent advancements in the areas of process systems and biochemical engineering have provided the tools necessary to study and design these continuous biochemical systems to maximize productivity and substrate utilization while reducing capital and operating costs. The first goal of this thesis is to propose a novel strategy for the continuous biochemical production of pharmaceuticals. The structural complexity of most pharmaceutical compounds makes chemical synthesis a difficult option, facilitating the need for their biological production. To this end, a continuous, multi-feed bioreactor system composed of multiple independently controlled feeds for substrate(s) and media is proposed to freely manipulate the bioreactor dilution rate and substrate concentrations. The optimal feed flow rates are determined through the solution to an optimal control problem where the kinetic models describing the time-variant system states are used as constraints. This new bioreactor paradigm is exemplified through the batch and continuous cultivation of β-carotene, a representative product of the mevalonate pathway, using Saccharomyces cerevisiae strain mutant SM14. The second goal of this thesis is to design continuous, biochemical processes capable of economically producing alternative liquid fuels. The large-scale, continuous production of ethanol via consolidated bioprocessing (CBP) is examined. Optimal process topologies for the CBP technology selected from a superstructure considering multiple biomass feeds, chosen from those available across the United States, and multiple prospective pretreatment technologies. Similarly, the production of butanol via acetone-butanol-ethanol (ABE) fermentation is explored using process intensification to improve process productivity and profitability. To overcome the inhibitory nature of the butanol product, the multi-feed bioreactor paradigm developed for pharmaceutical production is utilized with in situ gas stripping to simultaneously provide dilution effects and selectively remove the volatile ABE components. Optimal control and process synthesis techniques are utilized to determine the benefits of gas stripping and design a butanol production process guaranteed to be profitable

On the controllability of fermentation systems

This thesis concerns the controllability of fermentation processes. Fermentation processes are often described by unstructured process models. A control system can be used to reduce the effect of the uncertainties and disturbances. A process is called controllable if a control system satisfying suitably defined control objectives can be found. Controllability measures based on linear process models are identified. The idealised control objective for perfect control allows fast evaluation of the controllability measures. These measures are applied to compare different designs of a continuous fermentation process by identifying the controllability properties of the process design. The operational mode of fed batch fermentations is inherently dynamic. General control system design methods are not readily applicable to such systems. This work presents an approach for the design of robust controllers suitable for these processes. The control objective is to satisfy a set of robustness constraints for a given set of model uncertainties and disturbances. The optimal operation and design problems are combined into a single optimal control problem. The controller design is integrated into the process design problem formulation. In this way the control system and the process are designed simultaneously. Different problem formulations are investigated. The proposed approach is demonstrated on complex fermentation models. The resulting operating strategies are controllable with respect to the aims of control

Simulation and optimization of dynamic flux balance analysis models using an interior point method reformulation

This work presents a novel, differentiable, way of solving dynamic Flux Balance Analysis (dFBA) problems by embedding flux balance analysis of metabolic network models within lumped bulk kinetics for biochemical processes. The proposed methodology utilizes transformation of the bounds of the embedded linear programming problem of flux balance analysis via a logarithmic barrier (interior point) approach. By exploiting the first-order optimality conditions of the interior-point problem, and with further transformations, the approach results in a system of implicit ordinary differential equations. Results from four case studies, show that the CPU and wall-times obtained using the proposed method are competitive with existing state-of-the-art approaches for solving dFBA simulations, for problem sizes up to genome-scale. The differentiability of the proposed approach allows, using existing commercial packages, its application to the optimal control of dFBA problems at a genome-scale size, thus outperforming existing formulations as shown by two dynamic optimization case studies.• R. Conejeros would like to thank CONICYT’s research grant FONDECYT 1151295 for funding this research. • F. Scott gratefully acknowledges financial support from CONICYT (Proyectos REDES ETAPA INICIAL, Convocatoria 2017, REDI170254)

Una Simulación de la cinética de fermentación etanólica tipo lote alimentado utilizando el método Runge Kutta

Los procesos de fermentación etanólica a nivel industrial más difundidos son los del tipo lote alimentado. El objetivo del presente trabajo, es simular este proceso y determinar los resultados finales o valores máximos de las variables más importantes. Se establecen como base los parámetros cinéticos biológicos de las referencias para Saccharomyces cerevisiae. La metodología empleada para deducir los modelos matemáticos son los balances globales de masa, de consumo de sustrato, de producción de etanol, de crecimiento de las levaduras y el de energía. Los modelamientos requieren la utilización de diferenciales ordinarias cuya resolución analítica es compleja; por ello, se propone el método númerico de Runge Kutta de cuarto orden, el cual se puede llevar a cabo en una hoja de cálculo o en el software Polymath. Según los datos ingresados a las ecuaciones, las concentraciones finales fueron de 74,06 g/L, 30,93 g/L, -0,02 g/L para etanol, levadura y sustrato respectivamente y la temperatura máxima alcanzada fue de 34,41 °C. &nbsp

Experimental and artificial intelligence modelling study of oil palm trunk sap fermentation

© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/en14082137Five major operations for the conversion of lignocellulosic biomasses into bioethanol are pre-treatment, detoxification, hydrolysis, fermentation, and distillation. The fermentation process is a significant biological step to transform lignocellulose into biofuel. The interactions of biochemical networks and their uncertainty and nonlinearity that occur during fermentation processes are major problems for experts developing accurate bioprocess models. In this study, mechanical processing and pre-treatment on the palm trunk were done before fermentation. Analysis was performed on the fresh palm sap and the fermented sap to determine the composition. The analysis for total sugar content was done using high-performance liquid chromatography (HPLC) and the percentage of alcohols by volume was determined using gas chromatography (GC). A model was also developed for the fermentation process based on the Adaptive-Network-Fuzzy Inference System (ANFIS) combined with particle swarm optimization (PSO) to predict bioethanol production in biomass fermentation of oil palm trunk sap. The model was used to find the best experimental conditions to achieve the maximum bioethanol concentration. Graphical sensitivity analysis techniques were also used to identify the most effective parameters in the bioethanol process.This work supported by the Ministry of Education Malaysia through a Research University Grant of the University Technology Malaysia (UTM) (Award Number: Rk430000.7743.4J010).Published versio

The development of a weighted directed graph model for dynamic systems and application of Dijkstra’s algorithm to solve optimal control problems.

Master of Science (Chemical Engineering). University of KwaZulu-Natal. Durban, 2017.Optimal control problems are frequently encountered in chemical engineering process control applications as a result of the drive for more regulatory compliant, efficient and economical operation of chemical processes. Despite the significant advancements that have been made in Optimal Control Theory and the development of methods to solve this class of optimization problems, limitations in their applicability to non-linear systems inherent in chemical process unit operations still remains a challenge, particularly in determining a globally optimal solution and solutions to systems that contain state constraints. The objective of this thesis was to develop a method for modelling a chemical process based dynamic system as a graph so that an optimal control problem based on the system can be solved as a shortest path graph search problem by applying Dijkstra’s Algorithm. Dijkstra’s algorithm was selected as it is proven to be a robust and global optimal solution based algorithm for solving the shortest path graph search problem in various applications. In the developed approach, the chemical process dynamic system was modelled as a weighted directed graph and the continuous optimal control problem was reformulated as graph search problem by applying appropriate finite discretization and graph theoretic modelling techniques. The objective functional and constraints of an optimal control problem were successfully incorporated into the developed weighted directed graph model and the graph was optimized to represent the optimal transitions between the states of the dynamic system, resulting in an Optimal State Transition Graph (OST Graph). The optimal control solution for shifting the system from an initial state to every other achievable state for the dynamic system was determined by applying Dijkstra’s Algorithm to the OST Graph. The developed OST Graph-Dijkstra’s Algorithm optimal control solution approach successfully solved optimal control problems for a linear nuclear reactor system, a non-linear jacketed continuous stirred tank reactor system and a non-linear non-adiabatic batch reactor system. The optimal control solutions obtained by the developed approach were compared with solutions obtained by the variational calculus, Iterative Dynamic Programming and the globally optimal value-iteration based Dynamic Programming optimal control solution approaches. Results revealed that the developed OST Graph-Dijkstra’s Algorithm approach provided a 14.74% improvement in the optimality of the optimal control solution compared to the variational calculus solution approach, a 0.39% improvement compared to the Iterative Dynamic Programming approach and the exact same solution as the value–iteration Dynamic Programming approach. The computational runtimes for optimal control solutions determined by the OST Graph-Dijkstra’s Algorithm approach were 1 hr 58 min 33.19 s for the nuclear reactor system, 2 min 25.81s for the jacketed reactor system and 8.91s for the batch reactor system. It was concluded from this work that the proposed method is a promising approach for solving optimal control problems for chemical process-based dynamic systems

ADVANCES ON BILINEAR MODELING OF BIOCHEMICAL BATCH PROCESSES

[EN] This thesis is aimed to study the implications of the statistical modeling approaches proposed for the bilinear modeling of batch processes, develop new techniques to overcome some of the problems that have not been yet solved and apply them to data of biochemical processes. The study, discussion and development of the new methods revolve around the four steps of the modeling cycle, from the alignment, preprocessing and calibration of batch data to the monitoring of batches trajectories. Special attention is given to the problem of the batch synchronization, and its effect on the modeling from different angles. The manuscript has been divided into four blocks. First, a state-of- the-art of the latent structures based-models in continuous and batch processes and traditional univariate and multivariate statistical process control systems is carried out. The second block of the thesis is devoted to the preprocessing of batch data, in particular, to the equalization and synchronization of batch trajectories. The first section addresses the problem of the lack of equalization in the variable trajectories. The different types of unequalization scenarios that practitioners might finnd in batch processes are discussed and the solutions to equalize batch data are introduced. In the second section, a theoretical study of the nature of batch processes and of the synchronization of batch trajectories as a prior step to bilinear modeling is carried out. The topics under discussion are i) whether the same synchronization approach must be applied to batch data in presence of different types of asynchronisms, and ii) whether synchronization is always required even though the length of the variable trajectories are constant across batches. To answer these questions, a thorough study of the most common types of asynchronisms that may be found in batch data is done. Furthermore, two new synchronization techniques are proposed to solve the current problems in post-batch and real-time synchronization. To improve fault detection and classification, new unsupervised control charts and supervised fault classifiers based on the information generated by the batch synchronization are also proposed. In the third block of the manuscript, a research work is performed on the parameter stability associated with the most used synchronization methods and principal component analysis (PCA)-based Batch Multivariate Statistical Process Control methods. The results of this study have revealed that accuracy in batch synchronization has a profound impact on the PCA model parameters stability. Also, the parameter stability is closely related to the type of preprocessing performed in batch data, and the type of model and unfolding used to transform the three-way data structure to two-way. The setting of the parameter stability, the source of variability remaining after preprocessing and the process dynamics should be balanced in such a way that multivariate statistical models are accurate in fault detection and diagnosis and/or in online prediction. Finally, the fourth block introduces a graphical user-friendly interface developed in Matlab code for batch process understanding and monitoring. To perform multivariate analysis, the last developments in process chemometrics, including the methods proposed in this thesis, are implemented.[ES] La presente tesis doctoral tiene como objetivo estudiar las implicaciones de los métodos estadísticos propuestos para la modelización bilineal de procesos por lotes, el desarrollo de nuevas técnicas para solucionar algunos de los problemas más complejos aún por resolver en esta línea de investigación y aplicar los nuevos métodos a datos provenientes de procesos bioquímicos para su evaluación estadística. El estudio, la discusión y el desarrollo de los nuevos métodos giran en torno a las cuatro fases del ciclo de modelización: desde la sincronización, ecualización, preprocesamiento y calibración de los datos, a la monitorización de las trayectorias de las variables del proceso. Se presta especial atención al problema de la sincronización y su efecto en la modelización estadística desde distintas perspectivas. El manuscrito se ha dividido en cuatro grandes bloques. En primer lugar, se realiza una revisión bibliográfica de las técnicas de proyección sobre estructuras latentes para su aplicación en procesos continuos y por lotes, y del diseño de sistemas de control basados en modelos estadísticos multivariantes. El segundo bloque del documento versa sobre el preprocesamiento de los datos, en concreto, sobre la ecualización y la sincronización. La primera parte aborda el problema de la falta de ecualización en las trayectorias de las variables. Se discuten las diferentes políticas de muestreo que se pueden encontrar en procesos por lotes y las soluciones para ecualizar las variables. En la segunda parte de esta sección, se realiza un estudio teórico sobre la naturaleza de los procesos por lotes y de la sincronización de las trayectorias como paso previo a la modelización bilineal. Los temas bajo discusión son: i) si se debe utilizar el mismo enfoque de sincronización en lotes afectados por diferentes tipos de asincronismos, y ii) si la sincronización es siempre necesaria aún y cuando las trayectorias de las variables tienen la misma duración en todos los lotes. Para responder a estas preguntas, se lleva a cabo un estudio exhaustivo de los tipos más comunes de asincronismos que se pueden encontrar en este tipo de datos. Además, se proponen dos nuevas técnicas de sincronización para resolver los problemas existentes en aplicaciones post-morten y en tiempo real. Para mejorar la detección de fallos y la clasificación, también se proponen nuevos gráficos de control no supervisados y clasificadores de fallos supervisados en base a la información generada por la sincronización de los lotes. En el tercer bloque del manuscrito se realiza un estudio de la estabilidad de los parámetros asociados a los métodos de sincronización y a los métodos estadístico multivariante basados en el Análisis de Componentes Principales (PCA) más utilizados para el control de procesos. Los resultados de este estudio revelan que la precisión de la sincronización de las trayectorias tiene un impacto significativo en la estabilidad de los parámetros de los modelos PCA. Además, la estabilidad paramétrica está estrechamente relacionada con el tipo de preprocesamiento realizado en los datos de los lotes, el tipo de modelo a justado y el despliegue utilizado para transformar la estructura de datos de tres a dos dimensiones. El ajuste de la estabilidad de los parámetros, la fuente de variabilidad que queda después del preprocesamiento de los datos y la captura de las dinámicas del proceso deben ser a justados de forma equilibrada de tal manera que los modelos estadísticos multivariantes sean precisos en la detección y diagnóstico de fallos y/o en la predicción en tiempo real. Por último, el cuarto bloque del documento describe una interfaz gráfica de usuario que se ha desarrollado en código Matlab para la comprensión y la supervisión de procesos por lotes. Para llevar a cabo los análisis multivariantes, se han implementado los últimos desarrollos en la quimiometría de proc[CA] Aquesta tesi doctoral te com a objectiu estudiar les implicacions dels mètodes de modelització estadística proposats per a la modelització bilineal de processos per lots, el desenvolupament de noves tècniques per resoldre els problemes encara no resolts en aquesta línia de recerca i aplicar els nous mètodes a les dades dels processos bioquímics. L'estudi, la discussió i el desenvolupament dels nous mètodes giren entorn a les quatre fases del cicle de modelització, des de l'alineació, preprocessament i el calibratge de les dades provinents de lots, a la monitorització de les trajectòries. Es presta especial atenció al problema de la sincronització per lots, i el seu efecte sobre el modelatge des de diferents angles. El manuscrit s'ha dividit en quatre grans blocs. En primer lloc, es realitza una revisió bibliogràfica dels principals mètodes basats en tècniques de projecció sobre estructures latents en processos continus i per lots, així com dels sistemes de control estadístics multivariats. El segon bloc del document es dedica a la preprocessament de les dades provinents de lots, en particular, l' equalització i la sincronització. La primera part aborda el problema de la manca d'equalització en les trajectòries de les variables. Es discuteixen els diferents tipus d'escenaris en que les variables estan mesurades a distints intervals i les solucions per equalitzar-les en processos per lots. A la segona part d'aquesta secció es porta a terme un estudi teòric de la naturalesa dels processos per lots i de la sincronització de les trajectòries de lots com a pas previ al modelatge bilineal. Els temes en discussió són: i) si el mateix enfocament de sincronització ha de ser aplicat a les dades del lot en presència de diferents tipus de asincronismes, i ii) si la sincronització sempre es requereix tot i que la longitud de les trajectòries de les variables són constants en tots el lots. Per respondre a aquestes preguntes, es du a terme un estudi exhaustiu dels tipus més comuns de asincronismes que es poden trobar en les dades provinents de lots. A més, es proposen dues noves tècniques de sincronització per resoldre els problemes existents la sincronització post-morten i en temps real. Per millorar la detecció i la classificació de anomalies, també es proposen nous gràfics de control no supervisats i classificadors de falla supervisats dissenyats en base a la informació generada per la sincronització de lots. En el tercer bloc del manuscrit es realitza un treball de recerca sobre l'estabilitat dels paràmetres associats als mètodes de sincronització i als mètodes estadístics multivariats basats en l'Anàlisi de Components Principals (PCA) més utilitzats per al control de processos. Els resultats d'aquest estudi revelen que la precisió en la sincronització per lots te un profund impacte en l'estabilitat dels paràmetres dels models PCA. A més, l'estabilitat paramètrica està estretament relacionat amb el tipus de preprocessament realitzat en les dades provinents de lots, el tipus de model i el desplegament utilitzat per transformar l'estructura de dades de tres a dos dimensions. L'ajust de l'estabilitat dels paràmetres, la font de variabilitat que queda després del preprocessament i la captura de la dinàmica de procés ha de ser equilibrada de tal manera que els models estadístics multivariats són precisos en la detecció i diagnòstic de fallades i/o en la predicció en línia. Finalment, el quart bloc del document introdueix una interfície gràfica d'usuari que s'ha dissenyat e implementat en Matlab per a la comprensió i la supervisió de processos per lots. Per dur a terme aquestes anàlisis multivariats, s'han implementat els últims desenvolupaments en la quimiometria de processos, incloent-hi els mètodes proposats en aquesta tesi.González Martínez, JM. (2015). ADVANCES ON BILINEAR MODELING OF BIOCHEMICAL BATCH PROCESSES [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/55684TESISPremios Extraordinarios de tesis doctorale