Vytautas Galvanauskas

Kaunas University of Technology · Department of Automation

A model predictive control (MPC) method was investigated as a route to optimize and control the growth of E. coli BL21 (DE3) and biosynthesis of two different recombinant proteins (nerve growth factor NGF and coat protein of bacteriophage Qβ (Qβ-CP)). To determine the target trajectory for the E. coli cultivation process and estimate the model para...

Accurate estimations of the concentrations of soluble compounds are crucial for optimizing bioprocesses involving Escherichia coli (E. coli). This study proposes a hybrid model structure that leverages off-gas analysis data and physiological parameters, including the average biomass age and specific growth rate, to estimate soluble compounds such a...

Recombinant hepatitis B core antigen (HBcAg) molecules, produced in heterologous expression systems, self-assemble into highly homogenous and non-infectious virus-like particles (VLPs) that are under extensive research for biomedical applications. HBcAg production in the methylotrophic yeast P. pastoris has been well documented; however, productivi...

Docosahexaenoic acid (DHA) is one of the most important long-chain polyunsaturated fatty acids (LC-PUFAs), with numerous health benefits. Crypthecodinium cohnii, a marine heterotrophic dinoflagellate, is successfully used for the industrial production of DHA because it can accumulate DHA at high concentrations within the cells. Glycerol is an inter...

The article proposes a combined control scheme for the control of the important bioprocess variables that can be relatively easily implemented in industrial bioreactors and provides opportunities to significantly improve the quality of the basic control systems. The proposed combined control scheme includes feedback PI controller, feedforward compe...

An adaptive control system for the set-point control and disturbance rejection of biotechnological-process parameters is presented. The gain scheduling of PID (PI) controller parameters is based on only controller input/output signals and does not require additional measurement of process variables for controller-parameter adaptation. Realization o...

Microbial biomass concentration is a key bioprocess parameter, estimated using various labor, operator and process cross-sensitive techniques, analyzed in a broad context and therefore the subject of correct interpretation. In this paper, the authors present the results of P. pastoris cell density estimation based on off-line (optical density, wet/...

This article presents the development and application of a distinct adaptive control algorithm that is based on fuzzy logic and was used to control the specific growth rate (SGR) in a fed-batch biotechnological process. The developed control algorithm was compared with two adaptive control systems that were based on a model-free adaptive technique...

Background: The focus of this study is online estimation of biomass concentration in fed-batch cultures. It describes a bioengineering software solution, which is explored for Escherichia coli and Saccharomyces cerevisiae fed-batch cultures. The experimental investigation of both cultures presents experimental validation results since the start of...

This contribution discusses the main challenges related to successful application of automatic control systems used to control specific growth rate in industrial biotechnological processes. It is emphasized that, after the implementation of basic automatic control systems, primary attention shall be paid to the specific growth rate control systems...

To date, practical application of mathematical models for model-based design of stem cell expansion processes is limited. Nevertheless, the first attempts show vast potential of this approach for the improvement of expansion process performance. This article presents the developed dynamic kinetic model of the human induced pluripotent stem cell exp...

For historic reasons, industrial knowledge of reproducibility and restrictions imposed by regulations, open-loop feeding control approaches dominate in industrial fed-batch cultivation processes. In this study, a generic gray box biomass modeling procedure uses relative entropy as a key to approach the posterior similarly to how prior distribution...

Implementation of model-based practices for process development, control, automation, standardization, and validation are important factors for therapeutic and industrial applications of human pluripotent stem cells. As robust cultivation strategies for pluripotent stem cell expansion and differentiation have yet to be determined, process developme...

A developed solution for fed-batch process modeling and model predictive control (MPC), facilitating good manufacturing practice (GMP) based on process elaboration, control, and validation, is presented in the paper. The step-by-step evolution of the so-called “golden batch” optimal biomass growth profile and its control during the process is demon...

A developed solution for fed-batch process modeling and model predictive control (MPC), facilitating good manufacturing practice (GMP) based on process elaboration, control, and validation, is presented in the paper. The step-by-step evolution of the so-called “golden batch” optimal biomass growth profile and its control during the process is demon...

A developed solution for fed-batch process modeling and model predictive control (MPC), facilitating good manufacturing practice (GMP) based on process elaboration, control, and validation, is presented in the paper. The step-by-step evolution of the so-called “golden batch” optimal biomass growth profile and its control during the process is demon...

A control system for set-point control of microbial cultivation process parameters is developed, in which a tendency model is applied for controller adaptation to process nonlinearity and time-varying operating conditions. The tendency model is updated on-line and introduced into control algorithm for prediction of steady-state control action and r...

An inferential control system has been developed for off-gas analysis-based control of fed-batch microbial cultivation process to follow a desired biomass growth trajectory, which is an important objective in many cultivation processes. The control system exploits an original specific growth rate estimator from the oxygen uptake rate on-line measur...

Optimization of the microalgae cultivation process and of the bioprocess in general traditionally starts with cultivation experiments in flasks. Then the scale-up follows, when the process from flasks is transferred into a laboratory-scale bioreactor, in which further experiments are performed before developing the process in a pilot-scale reactor....

There are many factors that can affect microalgae growth. In this research, four different groups of experiments were set up in order to determine the influence of different mixing conditions, CO2 concentration and light intensities on Desmodesmus communis growth. The range of CO2 concentration in the air - CO2 mixture was 0–16 v/v%, light intensit...

This report highlights the drivers, challenges, and enablers of the hybrid modeling applications in biopharmaceutical industry. It is a summary of an expert panel discussion of European academics and industrialists with relevant scientific and engineering backgrounds. Hybrid modeling is viewed in its broader sense, namely as the integration of diff...

This paper proposes a bioprocess optimization procedure based on Relevance Vector Regression models and evolutionary programming technique. Relevance Vector Regression scheme allows developing a compact and stable data-based process model avoiding time-consuming modeling expenses. The model building and process optimization procedure could be done...

The researchers of BioVal project used the activated sludge process mathematical model with the goal to develop and test a control system for autotrophic biomass specific growth rate. The article describes the implementation of the biological wastewater treatment process model and control system into software SIMULINK (MATLAB). By means of the acti...

A model-based approach for optimization and cascade control of dissolved oxygen partial pressure (pO2) and maximization of biomass in fed-batch cultivations is presented. The procedure is based on the off-line model-based optimization of the optimal feeding rate profiles and the subsequent automatic pO2 control using a proposed cascade control tech...

In this article, application of state estimation techniques for indirect measurement of biomass concentration and specific growth rate in a typical fedbatch biotechnological process is discussed. Two stateof- the-art algorithms were implemented: Extended Kalman Filter (EKF) and feed-forward artificial neural networks (ANN) of various structures. Ox...

The Computational Intelligence is one of the main tools in biochemical network modeling that help predict or optimize engineering means of objectives to achieve. For this purpose, reconstructions (which tend to increase in number and size) of different genome-scale metabolic networks can be used. Consequently, realizing different tasks it is necess...

ModeRator is an online software tool for comparison of stoichiometric models written in COBRA-compatible format. Its main purpose is to detect the inconsistencies of complex models and to compare the models even without having Matlab and COBRA toolbox installed on a computer. The tool can be used online at http://biosystems.lv/moderator/ or hosted...

G. Oberauskas, V. Galvanauskas. Adaptive Control of H/N Ratio in Ammonia Production // Electronics and Electrical Engineering. - Kaunas: Technologija, 2011. - No. 9(115). - P. 87-90. A system for adaptive control of Hydrogen/Nitrogen (FUN) ratio in ammonia production is proposed. It ensures more accurate, robust control of H/N ratio under varying o...

An improved technique of hybrid modeling of fertilizers production processes for automatic control purpose is described. Design principles of mass balance systems for key components are outlined, and artificial neuron network (ANN) subsystems for modelling of absolute reaction rates are represented for ammonia production processes. The sensitivity...

A model-aided process design and supervision technique is proposed. Its efficiency is demonstrated by a nontrivial example, the development of a production process for the light chain of the antibody MAK33. This protein was expressed by the genetically modified E. coli B pUBS520 p12023 bacteria under the control of the tac promoter where lactose wa...

A novel flexible, cross-platform compatible system for monitoring and control of biotechnological processes is proposed. Different architectures of the proposed system are outlined and analyzed. They include bioreac-tor with digital control unit, computer and application. The application connects to bioreactor's controller, database, web applicatio...

A technique for hybrid model parameter identification based on evolutionary programming approach is applied on a hybrid model for chemical methanation production process. The computer simulation tests were performed using software tools created in Matlab (The MathWorks, Inc.) program environment. The hybrid model identification results are of suffi...

In the paper pH control problems in fed-batch biochemical processes are analyzed. Process mathematical model was based on the first principles and identified using available experimental data. An adaptive pH control sys-tem based on gain scheduling approach was proposed. Significant increase in control quality as compared to a standard PI control s...

The paper presents the results of model-based optimization of fed-batch culture Enterobacter aerogenes 17 E13 for maximization of biomass productivity. A mathematical model for the problem solving is developed using mass-balance conditions for cells' biomass and limiting substrate, relevant kinetic relationships for modeling the specific rates of b...

In this paper the detailed first principles mathematical model of industrial ammonia production process is elaborated. Mass balance equations and chemical reaction rate equations of the process are presented and analyzed. Computer simulation tests were performed using software tools created in Matlab program environment. The modelling results were...

In this paper problems of process control of ammonia producing plant are presented. The origin of these problems is analyzed and possible ways of their solution are presented. A hybrid model of the process is chosen as a possible solution. The key variables for the hybrid model of the process are defined and presented. Further steps of investigatio...

An approach for hybrid model identification based on sensitivity equations approach is tested on a hybrid model for biosurfactant production process. The computer simulations were performed using software tools for model-based design of biochemical processes elaborated in Matlab (The MathWorks, Inc.) environment. Possible difficulties and ways of p...

An approach for hybrid model parameter identification based on sensitivity equations approach is tested on a hybrid model for biosurfactant production process. The computer simulations were performed using software tools created in Matlab (The MathWorks, Inc.) environment. Possible difficulties and ways of practical implementation of the analyzed i...

A technique for hybrid model parameter identification based on sensitivity equations approach is tested on a hybrid model for biotechnological biosurfactant production process. The computer simulation tests were performed using software tools created in Matlab (The MathWorks, Inc.) program environment. Possible difficulties and ways of practical im...

A model-based optimization of an industrial fed-batch sugar crystallisation process is considered in this paper. The objective is to define the optimal profiles of the manipulated process inputs, the feeding rate of liquor/syrup and the steam supply rate, such that the crystal content and the crystal size distribution (CSD) measures at the end of t...

A problem of the model-based optimization of fed-batch cultivation process is solved for two control actions: feed-rate and dilution rate. A goal of optimization is to maximize the yield of cells' biomass at the end of cultivation cycle. Two alternative optimization methods, based on the maximum principle of Pontryagin and the finite dimensional op...

General framework for hybrid model based identification and optimization of biochemical processes is elaborated. An enhanced hybrid model of the fed-batch biosurfactant production process is presented. The evolutionary programming techniques are applied for the hybrid model identification and optimization of the process. High performance of the app...

Hybrid models aim to describe different components of a process in different ways. This makes sense when the corresponding knowledge to be represented is different as well. In this way, the most efficient representations can be chosen and, thus, the model performance can be increased significantly. From the various possible variants of hybrid model...

Fed-batch cultivation of Azotobacter vinelandii 21was optimized for biosurfactant production. Optimization of feed-rate time profile and concentration of nutrient medium components in feeding solution is based on a hybrid mathematical model consisting of mass-balance equations for biomass, biosurfactant, volume of cultural liquid and substrate comp...

An optimized fed-batch cultivation process for the production of the polyoma virus capsid protein VP1 in recombinant Escherichia coli BL21 bacteria is presented. The optimization procedure maximizing the amount of desired protein is based on a mathematical model. The model distinguishes an initial cell growth phase from a protein production phase i...

A time-efficient development procedure for the fermentation part of the production of recombinant proteins is proposed and applied to the specific case of the virus capsid protein VP1. It is based on an optimization procedure that combines model identification with process optimization in an evolutionary way. The model used is based on a mass balan...

Production of recombinant proteins using different host systems may lead to a different performance with respect to productivity or selectivity. Therefore, the conditions under which the systems perform may be different A comparison between two systems can only be made when both are cultivated at their optimal conditions. In order to make such comp...

A model-based feed-rate profile optimization problem is discussed for the fed-batch recombinant protein production. Two optimization procedures, an evolutionary programming technique and a simplified method using the dynamic programming concept, are discussed and compared. Modeling as well as experimental results are presented.

The open loop optimization of biochemical processes is discussed. The two optimization approaches: optimization based on Pontriagin's principle of maximum and evolutionary programming technique, are presented and compared. As a concrete example the labor scale fed-batch E.coli biomass production process is analyzed. The application of the evolution...

Fed-batch production processes for recombinant proteins are of the prime importance in modern biotechnology. In order to run the high performance process, it is necessary to keep it in optimal path. Nevertheless, at present there is no reliable methods for the on-line determination of key process variables and to use estimation results for control...

Many indirect biomass estimation techniques have been discussed in the literature; however, a comparison of the applicability of these methods for bioprocess control purposes has not been discussed comprehensively. In this paper, four different uncomplicated biomass measurement techniques were directly compared with the conventional biomass dry wei...

In this paper a simple design procedure is used to enhance the performance of a biotechnical cultivation process. A model supported approach is proposed. It starts with a simple classical process model obtained from literature data, which is used to design the first experiment. Then, the main procedure is an iteration of (i) improving the model mak...

In modern biotechnology the specific biomass growth rate () is a key factor influencing the productivity of bioprocess, e.g. recombinant fed-batch cultivation processes. For the process improvement it is desirable to determine an optimal  profile by means of open loop optimization techniques and then, using closed loop control, to keep the desire...

A simple design procedure is proposed that can be used to enhance the performance of a biological cultivation process. The model-supported method starts with a simple model. This is used to design first experiment, i.e., to calculate such a control profile that improves the process performance. The results of the experiment are then used to update...

Fast and reliable design of the new processes is the experiment design theory can be effectively applied to optimize the solving procedure. However, optimization of dynamical biotechnological processes is quite industrial biotechnology. For solving of static optimization problems the complicated problem because the classical experiment planning the...