Evolutionary optimization of a fed-batch penicillin fermentation process

This paper presents a genetic algorithms approach for the optimization of a fed-batch penicillin fermentation process. A customized float-encoding genetic algorithm is developed and implemented to a benchmark fed-batch penicillin fermentation process. Off-line optimization of the initial conditions and set points are carried out in two stages for a single variable and multiple variables. Further investigations with online optimization have been carried out to demonstrate that the yield can be significantly improved with an optimal feed rate profile. The results have shown that the proposed approaches can be successfully applied to optimization problems of fed-batch fermentation to improve the operation of such processes

Optimization of fed-batch fermentation processes with bio-inspired algorithms

The optimization of the feeding trajectories in fed-batch fermentation processes is a complex problem that has gained attention given its significant economical impact. A number of bio-inspired algorithms have approached this task with considerable success, but systematic and statistically significant comparisons of the different alternatives are still lacking. In this paper, the performance of different metaheuristics, such as Evolutionary Algorithms (EAs), Differential Evolution (DE) and Particle Swarm Optimization (PSO) is compared, resorting to several case studies taken from literature and conducting a thorough statistical validation of the results. DE obtains the best overall performance, showing a consistent ability to find good solutions and presenting a good convergence speed, with the DE/rand variants being the ones with the best performance. A freely available computational application, OptFerm, is described that provides an interface allowing users to apply the proposed methods to their own models and data.The work is partially funded by ERDF - European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the FCT (Portuguese Foundation for Science and Technology) within projects Ref. COMPETE FCOMP-01-0124-FEDER-015079 and PEst-OE/ES/UI0752/2011

Data-driven Soft Sensors in the Process Industry

In the last two decades Soft Sensors established themselves as a valuable alternative to the traditional means for the acquisition of critical process variables, process monitoring and other tasks which are related to process control. This paper discusses characteristics of the process industry data which are critical for the development of data-driven Soft Sensors. These characteristics are common to a large number of process industry fields, like the chemical industry, bioprocess industry, steel industry, etc. The focus of this work is put on the data-driven Soft Sensors because of their growing popularity, already demonstrated usefulness and huge, though yet not completely realised, potential. A comprehensive selection of case studies covering the three most important Soft Sensor application fields, a general introduction to the most popular Soft Sensor modelling techniques as well as a discussion of some open issues in the Soft Sensor development and maintenance and their possible solutions are the main contributions of this work

Stochastic Optimization of Bioreactor Control Policies Using a Markov Decision Process Model

Biopharmaceuticals are the fastest-growing segment of the pharmaceutical industry. Their manufacture is complicated by the uncertainty exhibited therein. Scholars have studied the planning and operation of such production systems under some uncertainties, but the simultaneous consideration of fermentation and resin yield uncertainty is lacking so-far. To study the optimal operation of biopharmaceutical production and purification systems under these uncertainties, a stochastic, dynamic approach is necessary. This thesis provides such a model by extending an existing discrete state-space, infinite horizon Markov decision process model of upstream fermentation. Tissue Plasminogen Activator fermentation and chromatography was implemented. This example was used to discuss the optimal policy for operating different fermentation setups. The average per-cycle operating profit of a serial setup was 1,272 $; the parallel setup produced negative average rewards. Managerial insights were derived from a comparison to a basic, titer maximizing policy and process sensitivities. In conclusion, the integrated stochastic optimization of biopharma production and purification control aids decision making. However, the model assumptions pose room for further studies. Keywords: Markov decision process; biopharmaceuticals production; fermentation uncertainty; chromatography resin; stochastic performance decay

Estimation of biochemical variables using quantumbehaved particle swarm optimization (QPSO)-trained radius basis function neural network: A case study of fermentation process of L-glutamic acid

Due to the difficulties in the measurement of biochemical variables in fermentation process, softsensing model based on radius basis function neural network had been established for estimating the variables. To generate a more efficient neural network estimator, we employed the previously proposed quantum-behaved particle swarm optimization (QPSO) algorithm for neural network training. The experiment results of L-glutamic acid fermentation process showed that our established estimator could predict variables such as the concentrations of glucose, biomass and glutamic acid with higher accuracy than the estimator trained by the most widely used orthogonal least squares (OLS). According to its global convergence, QPSO generated a group of more proper network parameters than the most popular OLS. Thus, QPSO-RBF estimator was more favorable to the control and fault diagnosis of the fermentation process, and consequently, it increased the yield of fermentation.Key words: Soft-sensing model, quantum-behaved particle swarm optimization algorithm, neural network

Applications of Mathematical Models in Engineering

The most influential research topic in the twenty-first century seems to be mathematics, as it generates innovation in a wide range of research fields. It supports all engineering fields, but also areas such as medicine, healthcare, business, etc. Therefore, the intention of this Special Issue is to deal with mathematical works related to engineering and multidisciplinary problems. Modern developments in theoretical and applied science have widely depended our knowledge of the derivatives and integrals of the fractional order appearing in engineering practices. Therefore, one goal of this Special Issue is to focus on recent achievements and future challenges in the theory and applications of fractional calculus in engineering sciences. The special issue included some original research articles that address significant issues and contribute towards the development of new concepts, methodologies, applications, trends and knowledge in mathematics. Potential topics include, but are not limited to, the following: Fractional mathematical models; Computational methods for the fractional PDEs in engineering; New mathematical approaches, innovations and challenges in biotechnologies and biomedicine; Applied mathematics; Engineering research based on advanced mathematical tools

Optimal control of fed-batch fermentation processes

Optimisation of a fed-batch fermentation process typically uses the calculus of variations or Pontryagin's maximum principle to determine an optimal feed rate profile. This often results in a singular control problem and an open loop control structure. The singular feed rate is the optimal feed rate during the singular control period and is used to control the substrate concentration in the fermenter at an optimal level. This approach is supported by biological knowledge that biochemical reaction rates are controlled by the environmental conditions in the fermenter; in this case, the substrate concentration. Since an accurate neural net-based on-line estimation of the substrate concentration has recently become available and is currently employed in industry, we are therefore able to propose a method which makes use of this estimation. The proposed method divides the optimisation problem into two parts. First, an optimal substrate concentration profile which governs the biochemical reactions in the fermentation process is determined. Then a controller is designed to track the obtained optimal profile. Since the proposed method determines the optimal substrate concentration profile, the singular control problem is therefore avoided because the substrate concentration appears nonlinearly in the system equations. Also, the process is then operated in closed loop control of the substrate concentration. The proposed method is then called "closed loop optimal control". The proposed closed loop optimal control method is then compared with the open loop optimal feed rate profile method. The comparison simulations from both primary and secondary metabolite production processes show that both methods give similar performance in a case of perfect model while the closed loop optimal control provides better performance than the open loop method in a case of plant/model mismatch. The better performance of the closed loop optimal control is due to an ability to compensate for the modelling errors using feedback

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

Optimization of a fed-batch bioreactor for 1,3-propanediol production using hybrid nonlinear optimal control

A nonlinear hybrid system was proposed to describe the fed-batch bioconversion of glycerol to 1,3-propanediol with substrate open loop inputs and pH logic control in previous work [47]. The current work concerns the optimal control of this fed-batch process. We slightly modify the hybrid system to provide a more convenient mathematical description for the optimal control of the fed-batch culture. Taking the feeding instants and the terminal time as decision variables, we formulate an optimal control model with the productivity of 1,3-propanediol as the performance index. Inequality path constraints involved in the optimal control problem are transformed into a group of end-point constraints by introducing an auxiliary hybrid system. The original optimal control problem is associated with a family of approximation problems. The gradients of the cost functional and the end-point constraint functions are derived from the parametric sensitivity system. On this basis, we construct a gradient-based algorithm to solve the approximation problems. Numerical results show that the productivity of 1,3-propanediol can be increased considerably by employing our optimal control policy