Calorimetry is a robust method for online monitoring and controlling bioprocesses in stirred tank reactors. Up to now, reactor calorimeters have not been optimally constructed for pilot scale applications. Thus, the objective of this paper is to compare two different ways for designing reactor calorimeters and validate them. The "heat capacity" method based on the mass flow of the cooling liquid in the jacket was compared with the "heat transfer" method based on the heat transfer coefficient continuously measured in the cultivation of Escherichia coli VH33 in a 50 L stirred tank reactor. It was found that the values of the "heat transfer" method agreed very well with the calculated values from the oxygen consumption. By contrast, the curve of the "heat capacity" method deviated from that of the oxygen consumption calculated with the oxycaloric equivalent. In conclusion, the "heat transfer" method has been proven to have a higher degree of validity than the "heat capacity" method. Thus, it is a better and more robust means to measure heat generation of fermentations in stirred tank bioreactors on a pilot scale.
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http://dx.doi.org/10.1002/bit.24601 | DOI Listing |
Biotechnol Prog
January 2025
AdBIOPRO, VINNOVA Competence Centre for Advanced Bioproduction by Continuous Processing, Royal Institute of Technology (KTH), Stockholm, Sweden.
The possibility to produce recombinant adeno-associated virus (rAAV) by adherent HEK293T cells was studied in a stirred tank bioreactor (STR) culture of cell aggregates. A proof-of-concept of rAAV production was successfully demonstrated in a process where single cells were first expanded, then cell aggregates were formed by dilution into a different medium 1 day before triple plasmid transfection was conducted. An alternative approach for the STR inoculation using a seed taken from a high cell density perfusion (HCDP) culture was also investigated.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras, 2780901, Portugal.
Generation of upscaled quantities of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), for therapeutic or testing applications, is both expensive and time-consuming. Herein, a scalable bioprocess for hiPSC-CM expansion in stirred-tank bioreactors (STB) is developed. By combining the continuous activation of the Wnt pathway, through perfusion of CHIR99021, within a mild hypoxia environment, the expansion of hiPSC-CM as aggregates is maximized, reaching 4 billion of pure hiPSC-CM in 2L STB.
View Article and Find Full Text PDFWater Sci Technol
January 2025
Chair of Water Resources Management and Modeling of Hydrosystems, Technische Universität Berlin, Gustav-Meyer-Allee 25, Berlin 13355, Germany.
This study explores the computational fluid dynamics (CFD) simulation of oxygen (O) and hydrogen sulfide (HS) mass transfer in a highly turbulent stirring tank. Using the open-source software OpenFOAM, we extended three-dimensional two-phase flow solvers with a rotating mesh feature to model the mass transfer processes between the water and air phases. The accuracy of these simulations was validated against experimental data, demonstrating a strong agreement in the mass transfer rates of HS and O.
View Article and Find Full Text PDFJ Biol Eng
January 2025
Biochemical Engineering (AVT.BioVT), RWTH Aachen University, Aachen, Germany.
Background: For process development in mammalian cell cultivations, scale-up approaches are essential. A lot of studies concern the scale transfer between different-sized stirred tank reactors. However, process development usually starts in even smaller cultivation vessels like microtiter plates or shake flasks.
View Article and Find Full Text PDFSLAS Discov
January 2025
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12 2781-901 Oeiras, Portugal; ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Av. Republica, 2780-157, Oeiras, Portugal. Electronic address:
Primary human hepatocytes (PHHs) are the preferred cell source to address liver function. Despite originating from the native tissue, one of the bottlenecks when using primary material is the donor-to-donor variability. Cryopreserved PHHs offer a high number of cells from the same donor and standardization of cell isolation and cryopreservation procedures, mitigating some of the inter-donor variability.
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