Volume 19, supplement 1
75th Anniversary of Professor Stoyan Tzonkov, Honorary Chief Editor of the International Journal Bioautomation
Bioprocess systems
Microbioreactors for Cell Cultures: Analysis, Modeling, Control, Applications and BeyondS1-S42
Pratap R. Patnaik
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Microbioreactors offer many advantages over macro-scale reactors for the screening and cultivation of microbial cultures. However, some weaknesses of microbioreactors are yet to be overcome. Optimum mixing under laminar flow, miniaturized on-line measurements and control, integration of upstream and downstream microdevices with the microbioreactor on a single chip, and adequate mathematical models to optimize the performance are some major issues that need to be resolved. Nevertheless, recent research indicates rapidly growing understanding of these problems and it has presented some promising solutions that have led to useful commercial applications. While specialized reviews have covered specific aspects of microbioprocesses exhaustively, the present article reviews microbioreactors per se in a holistic way, analyzing their functions both in a stand-alone setting and in conjunction with other microdevices. We also consider technological developments arising out of the standard microbioreactor and its possible future ramifications.
Constructing Optical Biosensor Based on Multienzyme System Tyrosinase/Horseradish PeroxidaseS43-S50
Lyubov Yotova, Spaska Yaneva
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By using sol-gel method, hybrid membranes were synthesized based on SiO2 and cellulose derivatives. Membranes showed good physical and mechanical properties as well as good biocompatibility. Onto hybrid membranes tyrosinase and horse radish peroxidase were immobilized and optical biosensor was constructed. The working principle of constructed biosensor was detection of oxygen consumption. The properties of constructed biosensors like linear range, life time and sensitivity were defined by modeling substrate - L-3,4-dihydroxyphenylalanine. The factors affecting the constructed optical biosensors were investigated. The results showed that a multienzyme system is capable of improving the constructed biosensor properties.
Analysis of Complex Behavior of Stem Cell Populations in Colonic CryptsS51-S68
Svetoslav Nikolov, Olaf Wolkenhauer, Julio Vera
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Mathematical models of the stem cell populations in colonic crypts can contribute to a better understanding of basic mechanisms underlying tissue organization. We here study the complex dynamic behaviour of a time delay model that describes stem cells in the niche of colonic crypts. We analyze the conditions for the various regimes that would lead to oscillations. The work presented here the first description of a chaotic system describing stem cell population dynamics in colonic crypts.
A Simple Mathematical Model of the Anaerobic Digestion of Wasted Fruits and Vegetables in Mesophilic ConditionsS69-S80
Elena Chorukova, Ivan Simeonov
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Anaerobic digestion is an effective biotechnological process for treatment of different agricultural, municipal and industrial wastes. Use of mathematical models is a powerful tool for investigations and optimisation of the anaerobic digestion. In this paper a simple mathematical model of the anaerobic digestion of wasted fruits and vegetables was developed and verified experimentally and by computer simulations using Simulink. A three-step mass-balance model was considered including the gas phase. The parameter identification was based on a set of 150 days of dynamical experiments in a laboratory bioreactor. Two step identification procedure to estimate 4 model parameters is presented. The results of 15 days of experiment in a pilot-scale bioreactor were then used to validate the model.
Modelling of a Batch Whey Cultivation of Kluyveromyces marxianus var. lactis MC 5 with Investigation of Mass Transfer Processes in the BioreactorS81-S92
Mitko Petrov, Tatiana Ilkova, Juris Vanags
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This study presents a mathematical model of a batch fermentation of lactose oxidation from a natural substratum in a cultivation by the strain Kluyweromyces marxianus var. lactis MC 5. In the model of the process, the mass transfer in the bioreactor for oxygen concentration in the gas phase (GP) and in the liquid phase (LP) is based on the dispersion model of the GP. In addition, perfect mixing in LP is included. Nine models were investigated for specific growth rate and specific oxygen consumptions rate: Monod, Mink, Tessier, Aiba, Andrews, Haldane, Luong, Edward and Han-Levenspiel. In regard to the parameter estimation, the worst observed error was used for all experiments as an objective function. This approach is a special case of multi objective parameter estimation problems allowing the parameter estimation problem to become a min-max problem. The results obtained (values of criteria, relative error and statistics λ) for the specific growth rate showed that the best fit to experimental data is achieved when applying the Mink model. In a combination a Mink, and Monod, Mink, Luong, Haldane, and Han-Levenspiel are used for specific oxygen consumptions rate. Based on the investigation, it was discovered that the best fit belonged to the models of Mink and Haldane, Mink and Luong and Mink and Han-Levenspiel. Therefore, these particular models are used for modeling the batch processes.
Functional State Modelling of Cultivation Processes: Dissolved Oxygen Limitation StateS93-S112
Olympia Roeva, Tania Pencheva, Stoyan Tzonkov, Bernd Hitzmann
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A new functional state, namely dissolved oxygen limitation state for both bacteria Escherichia coli and yeast Saccharomyces cerevisiae fed-batch cultivation processes is presented in this study. Functional state modelling approach is applied to cultivation processes in order to overcome the main disadvantages of using global process model, namely complex model structure and a big number of model parameters. Alongwith the newly introduced dissolved oxygen limitation state, second acetate production state and first acetate production state are recognized during the fed-batch cultivation of E. coli, while mixed oxidative state and first ethanol production state are recognized during the fed-batch cultivation of S. cerevisiae. For all mentioned above functional states both structural and parameter identification is here performed based on experimental data of E. coli and S. cerevisiae fed-batch cultivations.
Intelligent Optimization of a Mixed Culture Cultivation ProcessS113-S124
Petia Koprinkova-Hristova, Georgi Kostov, Silviya Popova
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In the present paper a neural network approach called "Adaptive Critic Design" (ACD) was applied to optimal tuning of set point controllers of the three main substrates (sugar, nitrogen source and dissolved oxygen) for PHB production process. For approximation of the critic and the controllers a special kind of recurrent neural networks called Echo state networks (ESN) were used. Their structure allows fast training that will be of crucial importance in on-line applications. The critic network is trained to minimize the temporal difference error using Recursive Least Squares method. Two approaches - gradient and heuristic - were exploited for training of the controllers. The comparison is made with respect to achieved improvement of the utility function subject of optimization as well as with known expert strategy for control the PHB production process.

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