An Approach for the Estimation of Concentrations of Soluble Compounds in Bioprocesses.

Accurate estimations of the concentrations of soluble compounds are crucial for optimizing bioprocesses involving (). 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 as acetate and glutamate in fed-batch cultivations We used a hybrid recurrent neural network to establish the relationships between these parameters. To enhance the precision of the estimates, the model incorporates ensemble averaging and information gain.

High-level production of recombinant HBcAg virus-like particles in a mathematically modelled P. pastoris GS115 Mut bioreactor process under controlled residual methanol concentration.

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, productivity screening under various residual methanol levels has not been reported for bioreactor processes.

Kinetic and Stoichiometric Modeling-Based Analysis of Docosahexaenoic Acid (DHA) Production Potential by from Glycerol, Glucose and Ethanol.

Docosahexaenoic acid (DHA) is one of the most important long-chain polyunsaturated fatty acids (LC-PUFAs), with numerous health benefits. , 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 interesting renewable substrate for DHA production since it is a by-product of biodiesel production and other industries, and is globally generated in large quantities.

Application of and Soft-Sensors for Estimation of Recombinant GS115 Biomass Concentration: A Case Analysis of HBcAg (Mut) and HBsAg (Mut) Production Processes under Varying Conditions.

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 cell density estimation based on off-line (optical density, wet/dry cell weight concentration), (turbidity, permittivity), and soft-sensor (off-gas O/CO, alkali consumption) techniques. Cultivations were performed in a 5 L oxygen-enriched stirred tank bioreactor.

Kinetic modeling of human induced pluripotent stem cell expansion in suspension culture.

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 expansion process in suspension culture.

Generic estimator of biomass concentration for Escherichia coli and Saccharomyces cerevisiae fed-batch cultures based on cumulative oxygen consumption rate.

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 the bioprocess, i.

From Physics to Bioengineering: Microbial Cultivation Process Design and Feeding Rate Control Based on Relative Entropy Using Nuisance Time.

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 approaches the posterior distribution by the multivariate path of Lagrange multipliers, for which a description of a nuisance time is introduced. The ultimate purpose of this study was to develop a numerical semi-global convex optimization procedure that is dedicated to the calculation of feeding rate time profiles during the fed-batch cultivation processes.

Current state and perspectives in modeling and control of human pluripotent stem cell expansion processes in stirred-tank bioreactors.

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 development could be enhanced by application of mathematical models and advanced control systems to optimize growth conditions. Therefore, it is important to understand both the potential of possible applications and the apparent limitations of existing mathematical models to improve pluripotent stem cell cultivation technologies.

Hybrid modeling for quality by design and PAT-benefits and challenges of applications in biopharmaceutical industry.

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 different knowledge sources in form of parametric and nonparametric models into a hybrid semi-parametric model, for instance the integration of fundamental and data-driven models.