Bioreaktoren

Chmiel, H.; Weuster‐Botz, Dirk

doi:10.1007/978-3-662-54042-8_6

Cited by 6 publications

(6 citation statements)

References 154 publications

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“…with

{\overset{\cdot}{V}}_{g, in}

as the gas flow rate into the reactor, V L as the reaction volume, V m as the molar volume of an ideal gas (22.4 L mol −1 ), and x CO2,in , x O2,in , x CO2,out , and x O2,out being the concentrations of carbon dioxide and oxygen in the inlet gas (in) and the exhaust gas (out), respectively 55.…”

Section: Methodsmentioning

confidence: 99%

Co‐Cultivation of Aspergillus niger and Trichoderma reesei Enables Efficient Production of Enzymes for the Hydrolysis of Wheat Bran

Mittermeier

Hafner

XypoliaVasila

et al. 2022

Chemie Ingenieur Technik

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Agro‐residues like wheat bran may be a useful carbon source for fermentation processes. However, due to their composition, hydrolysis appears complex. A co‐cultivation process was established with the two fungi A. niger and T. reesei for the production of an adapted mixture of enzymes for hydrolysis. This enzyme solution reached a higher space‐time yield of sugars during the hydrolysis of wheat bran compared to enzymes from respective monocultures, demonstrating the potential of this co‐culture for the production of complementary enzyme mixtures for the hydrolysis of wheat bran.

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“…with

{\overset{\cdot}{V}}_{g, in}

Section: Methodsmentioning

confidence: 99%

Co‐Cultivation of Aspergillus niger and Trichoderma reesei Enables Efficient Production of Enzymes for the Hydrolysis of Wheat Bran

Mittermeier

Hafner

XypoliaVasila

et al. 2022

Chemie Ingenieur Technik

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“…K M,NTP represents an apparent K M,NTP , which includes possible competitive inhibition. 86 When the apparent Michaelis−Menten constants are used in eq 14, the competitive inhibition terms must not be included. To simplify the determination of the kinetic parameters, the initial reaction rates and the substrate concentrations used were plotted as a Lineweaver−Burk, Hanes−Woolf, and Eadie−Hofstee diagram, and a linear regression was performed.…”

Section: In Vitro Transcription and Modelmentioning

confidence: 99%

“…The Michaelis−Menten constants become relevant mainly when the substrate concentrations fall below the respective threshold of <100 times K m . 86 This is more likely the case as the reaction progresses, which is why it becomes especially important in the implementation of appropriate feeding strategies.…”

Section: Feeding and Optimization Strategiesmentioning

confidence: 99%

Digital Twin Fundamentals of mRNA In Vitro Transcription in Variable Scale Toward Autonomous Operation

Hengelbrock,

Schmidt,

Strube

2024

ACS Omega

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The COVID-19 pandemic caused the rapid development of mRNA (messenger ribonucleic acid) vaccines and new RNA-based therapeutic methods. However, the approval rate for candidates has the potential to be increased, with a significant number failing so far due to efficacy, safety, and manufacturing deficiencies, hindering equitable vaccine distribution during pandemics. This study focuses on optimizing the production of mRNA, a critical component of mRNA-based vaccines, using a scalable machine by investigating the key mechanisms of mRNA in vitro transcription. First, kinetic parameters for the mRNA production process were determined. The validity of the determination and the robustness of the model are demonstrated by predicting different reactions with and without substrate limitations as well as different transcripts. The optimized reaction conditions, including temperature, urea concentration, and concentration of reaction-enhancing additives, resulted in a 55% increase in mRNA yield with a 33% reduction in truncated mRNA. Additionally, the feasibility of a segmented flow approach allowed for high-throughput screening (HTS), enabling the production of 20 vaccine candidates within a short time frame, representing a 10-fold increase in productivity, compared to nonsegmented reactions limited by the residence time in the plug flow reactor. The findings presented for the first time here contribute to the development of a fully continuous and efficient manufacturing process for mRNA and other cell and gene therapy drugs/vaccine candidates as presented in our previous work, which discussed the integration of process analytical technologies and predictive process models in a Biopharma 4.0 facility to enable the production of clinical and large-scale doses, ensuring a rapid and resilient supply of critical therapeutics. The results in this study especially highlight that the same machine and equipment can be used for screening and manufacturing different drug candidates in continuous operation. By streamlining production and adhering to quality standards, this approach enhances the industry's ability to respond swiftly to pandemics and public health emergencies, addressing the urgent need for accessible and effective vaccines.

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“…The most important element is the stirring system, as it transfers the energy required for the mixing process to the fluid. It usually consists of an agitator shaft with one or more impellers on it that is inserted into the vessel through a sealed hole in the top or bottom, with the motor located outside the bioreactor (Menkel 1992;Hemrajani and Tatterson 2003;Reichert et al 2012;Chmiel and Weuster-Botz 2018). Differences between impeller types will not be discussed in detail in this review, since this has been well described elsewhere (Liepe et al 1998;Zlokarnik 2001;Nienow 2010;Buffo et al 2016;Fig. 1 Classical composition of a stirred tank bioreactor (4) equipped with a motor (1), mechanical seal (2), air inlet (3), shaft (5), baffles (6), impellers (7), double jacket for heat transfer (8), sparger (9) and bottom drain (10).…”

Section: Main Components Of Stirred Bioreactorsmentioning

confidence: 99%

An overview of drive systems and sealing types in stirred bioreactors used in biotechnological processes

Schirmer

Maschke

Pörtner

et al. 2021

Appl Microbiol Biotechnol

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No matter the scale, stirred tank bioreactors are the most commonly used systems in biotechnological production processes. Single-use and reusable systems are supplied by several manufacturers. The type, size, and number of impellers used in these systems have a significant influence on the characteristics and designs of bioreactors. Depending on the desired application, classic shaft-driven systems, bearing-mounted drives, or stirring elements that levitate freely in the vessel may be employed. In systems with drive shafts, process hygiene requirements also affect the type of seal used. For sensitive processes with high hygienic requirements, magnetic-driven stirring systems, which have been the focus of much research in recent years, are recommended. This review provides the reader with an overview of the most common agitation and seal types implemented in stirred bioreactor systems, highlights their advantages and disadvantages, and explains their possible fields of application. Special attention is paid to the development of magnetically driven agitators, which are widely used in reusable systems and are also becoming more and more important in their single-use counterparts.Key Points• Basic design of the most frequently used bioreactor type: the stirred tank bioreactor• Differences in most common seal types in stirred systems and fields of application• Comprehensive overview of commercially available bioreactor seal types• Increased use of magnetically driven agitation systems in single-use bioreactors

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Bioreaktoren

Cited by 6 publications

References 154 publications

Co‐Cultivation of Aspergillus niger and Trichoderma reesei Enables Efficient Production of Enzymes for the Hydrolysis of Wheat Bran

Co‐Cultivation of Aspergillus niger and Trichoderma reesei Enables Efficient Production of Enzymes for the Hydrolysis of Wheat Bran

Digital Twin Fundamentals of mRNA In Vitro Transcription in Variable Scale Toward Autonomous Operation

An overview of drive systems and sealing types in stirred bioreactors used in biotechnological processes

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