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Journal articles on the topic 'Complex fed-batch bioprocess'

Author: Grafiati

Published: 2 June 2025

Last updated: 31 July 2025

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1

Caramihai, Mihai, and Irina Severin. "Intelligent Techniques for Fed-Batch Bioprocess Control." Key Engineering Materials 467-469 (February 2011): 1478–81. http://dx.doi.org/10.4028/www.scientific.net/kem.467-469.1478.

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Bioprocesses are appreciated as difficult to control because their dynamic behavior is highly nonlinear and time varying, in particular, when they are operating in fed batch mode. For this kind of bioprocess where the mathematical model contains many structured and unstructured uncertainties, we try to combine different intelligent techniques based on natural syllogisms of these techniques. In order to obtain a high bioprocess productivity it is essential to accord the benefits of the classical control strategy (i.e. the analytical determination of the optimum) with the subjective bioprocess c

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2

Ivušić, Franjo, Tonči Rezić, and Božidar Šantek. "Heterotrophic Cultivation of Euglena gracilis in Stirred Tank Bioreactor: A Promising Bioprocess for Sustainable Paramylon Production." Molecules 27, no. 18 (2022): 5866. http://dx.doi.org/10.3390/molecules27185866.

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Paramylon is a valuable intracellular product of the microalgae Euglena gracilis, and it can accumulate in Euglena cells according to the cultivation conditions. For the sustainable production of paramylon and appropriate cell growth, different bioreactor processes and industrial byproducts can be considered as substrates. In this study, a complex medium with corn steep solid (CSS) was used, and various bioreactor processes (batch, fed batch, semicontinuous and continuous) were performed in order to maximize paramylon production in the microalgae Euglena gracilis. Compared to the batch, fed ba

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3

Castañeda, María Teresita, Sebastián Nuñez, Martín Jamilis, and Hernán De Battista. "Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis." Fermentation 11, no. 6 (2025): 354. https://doi.org/10.3390/fermentation11060354.

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Fed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. In this study, we developed a computational framework based on dynamic flux balance analysis and small-scale metabolic models to evaluate and optimize lipid production in Rhodosporidium toruloides strains. We proposed equations to estimate both the carbon and energy

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4

Fan, Qin, Giorgio Caserta, Christian Lorent, Oliver Lenz, Peter Neubauer, and Matthias Gimpel. "Optimization of Culture Conditions for Oxygen-Tolerant Regulatory [NiFe]-Hydrogenase Production from Ralstonia eutropha H16 in Escherichia coli." Microorganisms 9, no. 6 (2021): 1195. http://dx.doi.org/10.3390/microorganisms9061195.

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Hydrogenases are abundant metalloenzymes that catalyze the reversible conversion of molecular H2 into protons and electrons. Important achievements have been made over the past two decades in the understanding of these highly complex enzymes. However, most hydrogenases have low production yields requiring many efforts and high costs for cultivation limiting their investigation. Heterologous production of these hydrogenases in a robust and genetically tractable expression host is an attractive strategy to make these enzymes more accessible. In the present study, we chose the oxygen-tolerant H2-

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5

Hrnčiřík, Pavel. "Monitoring of Biopolymer Production Process Using Soft Sensors Based on Off-Gas Composition Analysis and Capacitance Measurement." Fermentation 7, no. 4 (2021): 318. http://dx.doi.org/10.3390/fermentation7040318.

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This paper focuses on the design of soft sensors for on-line monitoring of the biotechnological process of biopolymer production, in which biopolymers are accumulated in bacteria as an intracellular energy storage material. The proposed soft sensors for on-line estimation of the biopolymer concentration represent an interesting alternative to the traditional off-line analytical techniques of limited applicability for real-time process control. Due to the complexity of biochemical reactions, which make it difficult to create reasonably complex first-principle mathematical models, a data-driven

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6

Mihai, Caramihai, and Severin Irina. "Quality Fed-Batch Bioprocess Control A Case Study." August 28, 2009. https://doi.org/10.5281/zenodo.1084734.

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Bioprocesses are appreciated as difficult to control because their dynamic behavior is highly nonlinear and time varying, in particular, when they are operating in fed batch mode. The research objective of this study was to develop an appropriate control method for a complex bioprocess and to implement it on a laboratory plant. Hence, an intelligent control structure has been designed in order to produce biomass and to maximize the specific growth rate.

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7

Mihai, Caramihai, and Severin Irina. "Quality Fed-Batch Bioprocess Control A Case Study." International Journal of Information, Control and Computer Sciences 2.0, no. 8 (2009). https://doi.org/10.5281/zenodo.1335324.

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Bioprocesses are appreciated as difficult to control because their dynamic behavior is highly nonlinear and time varying, in particular, when they are operating in fed batch mode. The research objective of this study was to develop an appropriate control method for a complex bioprocess and to implement it on a laboratory plant. Hence, an intelligent control structure has been designed in order to produce biomass and to maximize the specific growth rate.

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8

Mihai, Caramihai Ana A. Chirvase, and Severin Irina. "Bioprocess Intelligent Control: A Case Study." August 23, 2011. https://doi.org/10.5281/zenodo.1059651.

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Bioprocesses are appreciated as difficult to control because their dynamic behavior is highly nonlinear and time varying, in particular, when they are operating in fed batch mode. The research objective of this study was to develop an appropriate control method for a complex bioprocess and to implement it on a laboratory plant. Hence, an intelligent control structure has been designed in order to produce biomass and to maximize the specific growth rate.

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9

Ivušić, Franjo, Tonci Rezic, and Božidar Šantek. "Heterotrophic Cultivation of Euglena gracilis in Stirred Tank Bioreactor: A Promising Bioprocess for Sustainable Paramylon Production." Molecules 27, no. 18 (2022). https://doi.org/10.3390/molecules27185866.

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Abstract:

Paramylon is a valuable intracellular product of the microalgae Euglena gracilis, and it can accumulate in Euglena cells according to the cultivation conditions. For the sustainable production of paramylon and appropriate cell growth, different bioreactor processes and industrial byproducts can be considered as substrates. In this study, a complex medium with corn steep solid (CSS) was used, and various bioreactor processes (batch, fed batch, semicontinuous and continuous) were performed in order to maximize paramylon production in the microalgae Euglena gracilis. Compared

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10

Jianwen, Yang, Chen Xiangguang, and Jin Huaiping. "Online prediction for contamination of chlortetracycline fermentation based on Dezert–Smarandache theory." March 13, 2015. https://doi.org/10.5281/zenodo.32225.

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Fermentative production of chlortetracycline is a complex fed-batch bioprocess. It generally takes over 90 h for cultivation and is often contaminated by undesired microorganisms. Once the fermentation system is contaminated to certain extent, the product quality and yieldwill be seriously affected, leading to a substantial economic loss.

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11

Huaiping, Jin, and Chen Xiangguang. "Online prediction for contamination of chlortetracycline fermentation based on Dezert-Smarandache theory." March 13, 2015. https://doi.org/10.5281/zenodo.22917.

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Fermentative production of chlortetracycline is a complex fed-batch bioprocess. It generally takes over 90h for cultivation and is often contaminated by undesired microorganisms. Once the fermentation system is contaminated to certain extent, the product quality and yield will be seriously affected, leading to a substantial economic loss. Using information fusion based on the Dezer-Smarandache theory, self-recursive wavelet neural network and unscented Kalman filter, a novel method for online prediction of contamination is developed. All state variables of culture process involving easy-to-mea

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12

"Development of Soft Sensors for Online Biomass Prediction in Production of Hepatitis B Vaccine." Biointerface Research in Applied Chemistry 13, no. 2 (2022): 195. http://dx.doi.org/10.33263/briac132.194.

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Neural networks can provide highly accurate and robust solutions for complex non-linear kinetic like bioprocess reactions. It is applied as a soft sensor in the biotechnology industry for measuring and analyzing parameters that can hardly be reached online, as well as the reproducibility of the product without significant deviation. This study attempted to obtain the best neural network structure for online estimation of P. pastoris yeast biomass, which is used to express the hepatitis B surface antigen (HBsAg). During the fed-batch fermentation process, the CO2 evolution rate (CEO), ammonia c

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13

McFarland, Kevin S., Kaitlin Hegadorn, Michael J. Betenbaugh, and Michael W. Handlogten. "Elevated endoplasmic reticulum pH is associated with high growth and bisAb aggregation in CHO cells." Biotechnology and Bioengineering, October 22, 2024. http://dx.doi.org/10.1002/bit.28866.

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AbstractChinese hamster ovary (CHO) bioprocesses, the dominant platform for therapeutic protein production, are increasingly used to produce complex multispecific proteins. Product quantity and quality are affected by intracellular conditions, but these are challenging to measure and often overlooked during process optimization studies. pH is known to impact quality attributes like protein aggregation across upstream and downstream processes, yet the effects of intracellular pH on cell culture performance are largely unknown. Recently, advances in protein biosensors have enabled investigations

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14

Calvillo, Álvaro, Teresa Pellicer, Marc Carnicer, and Antoni Planas. "Developing a single-stage continuous process strategy for vitamin B12 production with Propionibacterium freudenreichii." Microbial Cell Factories 22, no. 1 (2023). http://dx.doi.org/10.1186/s12934-023-02029-x.

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Abstract Background Vitamin B12 is a widely used compound in the feed and food, healthcare and medical industries that can only be produced by fermentation because of the complexity of its chemical synthesis. Besides, the use of Generally Recognized as Safe (GRAS) and Qualified Presumption of Safety (QPS) microorganisms, like Propionibacterium freudenreichii, especially non-GMO wild-type producers, are becoming an interesting alternative in markets where many final consumers have high health and ecological awareness. In this study, the production of vitamin B12 using the Propionibacterium freu

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15

Rohr, Katja, Lisa Gremm, Bertram Geinitz, et al. "Optimizing microbioreactor cultivation strategies for Trichoderma reesei: from batch to fed-batch operations." Microbial Cell Factories 23, no. 1 (2024). http://dx.doi.org/10.1186/s12934-024-02371-8.

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Abstract Background Filamentous fungi have long been recognized for their exceptional enzyme production capabilities. Among these, Trichoderma reesei has emerged as a key producer of various industrially relevant enzymes and is particularly known for the production of cellulases. Despite the availability of advanced gene editing techniques for T. reesei, the cultivation and characterization of resulting strain libraries remain challenging, necessitating well-defined and controlled conditions with higher throughput. Small-scale cultivation devices are popular for screening bacterial strain libr

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16

Dodia, Hardik, Vivek Mishra, Prajval Nakrani, et al. "Dynamic flux balance analysis of high cell density fed‐batch culture of Escherichia coli BL21 (DE3) with mass spectrometry‐based spent media analysis." Biotechnology and Bioengineering, January 12, 2024. http://dx.doi.org/10.1002/bit.28654.

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AbstractDynamic flux balance analysis (FBA) allows estimation of intracellular reaction rates using organism‐specific genome‐scale metabolic models (GSMM) and by assuming instantaneous pseudo‐steady states for processes that are inherently dynamic. This technique is well‐suited for industrial bioprocesses employing complex media characterized by a hierarchy of substrate uptake and product secretion. However, knowledge of exchange rates of many components of the media would be required to obtain meaningful results. Here, we performed spent media analysis using mass spectrometry coupled with liq

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17

Schollmeyer, Julia, Saskia Waldburger, Kendra Njo, et al. "Bioprocess development to produce a hyperthermostable S‐methyl‐5′‐thioadenosine phosphorylas in Escherichia coli." Biotechnology and Bioengineering, August 13, 2023. http://dx.doi.org/10.1002/bit.28526.

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AbstractNucleoside phosphorylases are important biocatalysts for the chemo‐enzymatic synthesis of nucleosides and their analogs which are, among others, used for the treatment of viral infections or cancer. S‐methyl‐5′‐thioadenosine phosphorylases (MTAP) are a group of nucleoside phosphorylases and the thermostable MTAP of Aeropyrum pernix (ApMTAP) was described to accept a wide range of modified nucleosides as substrates. Therefore, it is an interesting biocatalyst for the synthesis of nucleoside analogs for industrial and therapeutic applications. To date, thermostable nucleoside phosphoryla

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18

Schütte, Lina, and Ralf G. Berger. "Development of a Bioprocess for Squalene Production in Thraustochytrids." Lebensmittelchemie 79, S2 (2025). https://doi.org/10.1002/lemi.202552232.

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Squalene is a natural triterpene that has many applications in the pharmaceutical, cosmetic and food industry. The current production of this natural substance is problematic, as deep sea sharks are hunted for its extraction from shark liver oil. Extraction from certain lipid‐rich plants is possible, but requires large amounts of land, is seasonal and runs the risk of competing with food production. Therefore, this work deals with an alternative approach: The biotechnological squalene production by marine eukaryotes belonging to the thraustochytrid family.Thraustochytrids are unicellular eukar

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19

Ramos, João R. C., José Pinto, Gil Poiares‐Oliveira, Ludovic Peeters, Patrick Dumas, and Rui Oliveira. "Deep hybrid modeling of a HEK293 process: Combining long short‐term memory networks with first principles equations." Biotechnology and Bioengineering, February 11, 2024. http://dx.doi.org/10.1002/bit.28668.

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AbstractThe combination of physical equations with deep learning is becoming a promising methodology for bioprocess digitalization. In this paper, we investigate for the first time the combination of long short‐term memory (LSTM) networks with first principles equations in a hybrid workflow to describe human embryonic kidney 293 (HEK293) culture dynamics. Experimental data of 27 extracellular state variables in 20 fed‐batch HEK293 cultures were collected in a parallel high throughput 250 mL cultivation system in an industrial process development setting. The adaptive moment estimation method w

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20

Espinel‐Ríos, Sebastián, Bruno Morabito, Johannes Pohlodek, Katja Bettenbrock, Steffen Klamt, and Rolf Findeisen. "Toward a modeling, optimization, and predictive control framework for fed‐batch metabolic cybergenetics." Biotechnology and Bioengineering, November 9, 2023. http://dx.doi.org/10.1002/bit.28575.

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AbstractBiotechnology offers many opportunities for the sustainable manufacturing of valuable products. The toolbox to optimize bioprocesses includes extracellular process elements such as the bioreactor design and mode of operation, medium formulation, culture conditions, feeding rates, and so on. However, these elements are frequently insufficient for achieving optimal process performance or precise product composition. One can use metabolic and genetic engineering methods for optimization at the intracellular level. Nevertheless, those are often of static nature, failing when applied to dyn

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21

Reid, Jennifer, Manjit Haer, Airong Chen, et al. "Development of automated metabolite control using mid-infrared probe for bioprocesses and vaccine manufacturing." Journal of Industrial Microbiology and Biotechnology, June 11, 2024. http://dx.doi.org/10.1093/jimb/kuae019.

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Abstract Automation of metabolite control in fermenters is fundamental to develop vaccine manufacturing processes more quickly and robustly. We created an end-to-end process analytical technology (PAT) and quality by design (QbD) focused process by replacing manual control of metabolites during the development of fed-batch bioprocesses with a system that is highly adaptable, and automation enabled. Mid-infrared (MIR) spectroscopy with an attenuated total reflectance probe in-line, and simple linear regression using the Beer-Lambert Law, were developed to quantitate key metabolites (glucose and

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22

Fan, Qin, Saskia Waldburger, Peter Neubauer, Sebastian L. Riedel, and Matthias Gimpel. "Implementation of a high cell density fed-batch for heterologous production of active [NiFe]-hydrogenase in Escherichia coli bioreactor cultivations." Microbial Cell Factories 21, no. 1 (2022). http://dx.doi.org/10.1186/s12934-022-01919-w.

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Abstract Background O2-tolerant [NiFe]-hydrogenases offer tremendous potential for applications in H2-based technology. As these metalloenzymes undergo a complicated maturation process that requires a dedicated set of multiple accessory proteins, their heterologous production is challenging, thus hindering their fundamental understanding and the development of related applications. Taking these challenges into account, we selected the comparably simple regulatory [NiFe]-hydrogenase (RH) from Cupriavidus necator as a model for the development of bioprocesses for heterologous [NiFe]-hydrogenase

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23

Schaub, Jochen, Andreas Ankenbauer, Tobias Habicher, et al. "Process intensification in biopharmaceutical process development and production – an industrial perspective." Physical Sciences Reviews, November 13, 2023. http://dx.doi.org/10.1515/psr-2022-0113.

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Abstract Process intensification aims to increase productivity in biologics manufacturing. Significant progress has been made in academia, the biopharmaceutical industry, and by the regulatory guidance since the 2000s. Process intensification can include all unit operations of a drug substance manufacturing process. The applied upstream concepts have consequences on the downstream process (DSP). The DSP process must manage larger product amounts while ensuring the required quality and impurity profiles, and cope with the available time frame as per scheduling requirements in a facility. Furthe

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24

Kaplan, Nicholas A., Khondokar Nowshin Islam, Fiona C. Kanis, et al. "Simultaneous glucose and xylose utilization by an Escherichia coli catabolite repression mutant." Applied and Environmental Microbiology, January 30, 2024. http://dx.doi.org/10.1128/aem.02169-23.

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ABSTRACT As advances are made toward the industrial feasibility of mass-producing biofuels and commodity chemicals with sugar-fermenting microbes, high feedstock costs continue to inhibit commercial application. Hydrolyzed lignocellulosic biomass represents an ideal feedstock for these purposes as it is cheap and prevalent. However, many microbes, including Escherichia coli , struggle to efficiently utilize this mixture of hexose and pentose sugars due to the regulation of the carbon catabolite repression (CCR) system. CCR causes a sequential utilization of sugars, rather than simultaneous uti

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