Oxygen Mass Transfer in Biopharmaceutical Processes: Numerical and Experimental Approaches

Seidel, Stefan; Maschke, Rüdiger W.; Werner, Sören; Jossen, Valentin; Eibl, Dieter

doi:10.1002/cite.202000179

Cited by 41 publications

(46 citation statements)

References 257 publications

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“…In contrast to conventional sampling, OUR measurements can be performed with high-frequency and enable real-time adjustments of the process. Thus, OUR measurement was shown to be suited for cell line characterization ( Ramirez and Mutharasan, 1990 ; Deshpande and Heinzle, 2004 ; Huang et al, 2010 ; Seidel et al, 2021 ), the design of nutrient feeding strategies ( Kyung et al, 1994 ; Eyer et al, 1995 ; Zhou et al, 1997 ; Goldrick et al, 2018 ) and estimation of the viable cell concentration (VCC) ( Fleischaker and Sinskey, 1981 ; Yamada et al, 1990 ; Zhou et al, 1995 ; Kamen et al, 1996 ; Higareda et al, 1997 ; Galvez et al, 2012 ). In combination with VCC measurement, the OUR can be used to calculate cell-specific oxygen uptake rates (qO 2 ), which is a crucial parameter of every cell line ( Ruffieux et al, 1998 ).…”

Section: Introductionmentioning

confidence: 99%

Time-Resolved Monitoring of the Oxygen Transfer Rate of Chinese Hamster Ovary Cells Provides Insights Into Culture Behavior in Shake Flasks

Ihling

Munkler

Berg

et al. 2021

Front. Bioeng. Biotechnol.

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Cultivations of mammalian cells are routinely conducted in shake flasks. In contrast to instrumented bioreactors, reliable options for non-invasive, time-resolved monitoring of the culture status in shake flasks are lacking. The Respiration Activity Monitoring Respiration Activity Monitoring System system was used to determine the oxygen transfer rate (OTR) in shake flasks. It was proven that the OTR could be regarded as equal to the oxygen uptake rate as the change of the dissolved oxygen concentration in the liquid phase over time was negligibly small. Thus, monitoring the oxygen transfer rate (OTR) was used to increase the information content from shake flask experiments. The OTR of a Chinese hamster ovary cell line was monitored by applying electrochemical sensors. Glass flasks stoppered with cotton plugs and polycarbonate flasks stoppered with vent-caps were compared in terms of mass transfer characteristics and culture behavior. Similar mass transfer resistances were determined for both sterile closures. The OTR was found to be well reproducible within one experiment (standard deviation <10%). It correlated with changes in cell viability and depletion of carbon sources, thus, giving more profound insights into the cultivation process. Culture behavior in glass and polycarbonate flasks was identical. Monitoring of the OTR was applied to a second culture medium. Media differed in the maximum OTR reached during cultivation and in the time when all carbon sources were depleted. By applying non-invasive, parallelized, time-resolved monitoring of the OTR, the information content and amount of data from shake flask experiments was significantly increased compared to manual sampling and offline analysis. The potential of the technology for early-stage process development was demonstrated.

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Section: Introductionmentioning

confidence: 99%

Time-Resolved Monitoring of the Oxygen Transfer Rate of Chinese Hamster Ovary Cells Provides Insights Into Culture Behavior in Shake Flasks

Ihling

Munkler

Berg

et al. 2021

Front. Bioeng. Biotechnol.

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“…Multiphase systems, such as aerated bioreactors, pose a particular challenge in terms of modeling, but they can be modeled with different degrees of abstraction. A promising approach to modeling polydisperse systems is to couple CFD with population balance models (PBM) [7]. This allows size distributions of gas bubbles that occur due to break-up and coalescence to be modeled.…”

Section: Introductionmentioning

confidence: 99%

Influence of Interfacial Force Models and Population Balance Models on the kLa Value in Stirred Bioreactors

Seidel

Eibl

2021

Processes

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Optimal oxygen supply is vitally important for the cultivation of aerobically growing cells, as it has a direct influence on cell growth and product formation. A process engineering parameter directly related to oxygen supply is the volumetric oxygen mass transfer coefficient kLa. It is the influences on kLa and computing time of different interfacial force and population balance models in stirred bioreactors that have been evaluated in this study. For this investigation, the OpenFOAM 7 open-source toolbox was utilized. Firstly, the Euler–Euler model with a constant bubble diameter was applied to a 2L scale bioreactor to statistically examine the influence of different interfacial models on the kLa value. It was shown that the kL model and the constant bubble diameter have the greatest influence on the calculated kLa value. To eliminate the problem of a constant bubble diameter and to take effects such as bubble breakup and coalescence into account, the Euler–Euler model was coupled with population balance models (PBM). For this purpose, four coalescence and five bubble breakup models were examined. Ultimately, it was established that, for all of the models tested, coupling computational fluid dynamics (CFD) with PBM resulted in better agreement with the experimental data than using the Euler–Euler model. However, it should be noted that the higher accuracy of the PBM coupled models requires twice the computation time.

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“…[18] Given the importance and high interest in redox biocatalysis in organic synthesis, it is clear that accurate knowledge of oxygen (O2) transfer is critical for the control of many bioprocesses, especially on a sustainable and economically feasible industrial scale. [19] The oxygen transfer rates from air into water were already broadly described in the literature, [20] and recently, Ramesh et al report the measurement of oxygen transfer from air into various organic solvents. [21] The authors used the dynamic method with a novel solvent resistant optical sensor and describe for the first time online oxygen measurements (concentrations and transfer rates) in organic media (toluene, tetrahydrofuran, dimethylformamide, methyl tert-butylether, cyclohexane, heptane, isooctane and water as reference).…”

Section: Introductionmentioning

confidence: 99%

Can Deep Eutectic Solvents Sustain Oxygen-Dependent Bioprocesses?—Measurements of Oxygen Transfer Rates

Zhang

Steininger

Meyer

et al. 2021

ACS Sustainable Chem. Eng.

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The oxygen transfer rate (OTR) of dioxygen to solutions describing the transport of oxygen gas from the gaseous phase into the liquid phase of a reaction system over a given period is an important measure for biotechnological applications. The OTRs have already been described for aqueous systems and also recently for organic and non-conventional media, whereas the OTRs of a novel class of solvents, deep eutectic solvents (DESs), have not been determined yet. In this contribution, we report for the first time on the OTRs of choline chloride:ethylene glycol (ChCl:EG, 'ethaline') and ethylammonium chloride:ethylene glycol (EAC:EG, 'ethethylaline') while using water as a reference. We applied the dynamic measurement method and found up to 11-fold lower volumetric mass transfer coefficient (kLa) for ethaline and 6-fold lower for ethethylaline when compared to water at 25°C. Furthermore, we investigated the effect temperature (35°C and 45°C) has on the kLa for those solvents. File list (2) download file view on ChemRxiv 2021-03-03_ChemRxiv_Manuscript.pdf (508.61 KiB) download file view on ChemRxiv 2021-03-03_ChemRxiv_SuppInfo.pdf (664.82 KiB) Can deep eutectic solvents sustain oxygen dependent bioprocesses? -Measurements of oxygen transfer rates

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Oxygen Mass Transfer in Biopharmaceutical Processes: Numerical and Experimental Approaches

Cited by 41 publications

References 257 publications

Time-Resolved Monitoring of the Oxygen Transfer Rate of Chinese Hamster Ovary Cells Provides Insights Into Culture Behavior in Shake Flasks

Time-Resolved Monitoring of the Oxygen Transfer Rate of Chinese Hamster Ovary Cells Provides Insights Into Culture Behavior in Shake Flasks

Influence of Interfacial Force Models and Population Balance Models on the kLa Value in Stirred Bioreactors

Can Deep Eutectic Solvents Sustain Oxygen-Dependent Bioprocesses?—Measurements of Oxygen Transfer Rates

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