A model for oxygen supply in fixed bed reactors with immobilized hybridoma cells

Pörtner, Ralf; Koop, Matthias

doi:10.1007/s004490050385

Cited by 10 publications

(3 citation statements)

References 29 publications

(44 reference statements)

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“…Maximum oxygen uptake rates have been measured approaching 100% confluency in 2D cultured cells, whereas those in 3D cultured systems have been at a lower confluency [5,8]. This difference could also be caused by the increased convection present in flow perfusion systems where oxygen delivery does not rely on diffusion, and there are lower external mass transport limitations [22,23]. The plateau reached at 450 µL/min may indicate that non-differentiating mesenchymal stem cells will reach a maximum value of oxygen consumption of 3 picomoles O 2 /hr/cell.…”

Section: Oxygen Uptake Rate (Our)mentioning

confidence: 99%

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Effects of Flow Rate on Mesenchymal Stem Cell Oxygen Consumption Rates in 3D Bone-Tissue-Engineered Constructs Cultured in Perfusion Bioreactor Systems

Felder

Simmons

Shambaugh

et al. 2020

Fluids

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Bone grafts represent a multibillion-dollar industry, with over a million grafts occurring each year. Common graft types are associated with issues such as donor site morbidity in autologous grafts and immunological response in allogenic grafts. Bone-tissue-engineered constructs are a logical approach to combat the issues commonly encountered with these bone grafting techniques. When creating bone-tissue-engineered constructs, monitoring systems are required to determine construct characteristics, such as cellularity and cell type. This study aims to expand on the current predictive metrics for these characteristics, specifically analyzing the effects of media flow rate on oxygen uptake rates (OURs) of mesenchymal stem cells seeded on poly(L-lactic acid) (PLLA) scaffolds cultured in a flow perfusion bioreactor. To do this, oxygen consumption rates were measured for cell/scaffold constructs at varying flow rates ranging from 150 to 750 microliters per minute. Residence time analyses were performed for this bioreactor at these flow rates. Average observed oxygen uptake rates of stem cells in perfusion bioreactors were shown to increase with increased oxygen availability at higher flow rates. The residence time analysis helped identify potential pitfalls in current bioreactor designs, such as the presence of channeling. Furthermore, this analysis shows that oxygen uptake rates have a strong linear correlation with residence times of media in the bioreactor setup, where cells were seen to exhibit a maximum oxygen uptake rate of 3 picomoles O 2 /hr/cell.

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Section: Oxygen Uptake Rate (Our)mentioning

confidence: 99%

“…Fluids 2020, 5, x 10 of 14 mass transport limitations [22,23]. The plateau reached at 450 L/min may indicate that nondifferentiating mesenchymal stem cells will reach a maximum value of oxygen consumption of 3 picomoles O2/hr/cell.…”

Section: Residence Time Distribution Analysismentioning

confidence: 99%

Effects of Flow Rate on Mesenchymal Stem Cell Oxygen Consumption Rates in 3D Bone-Tissue-Engineered Constructs Cultured in Perfusion Bioreactor Systems

Felder

Simmons

Shambaugh

et al. 2020

Fluids

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“…This is done to assure complete conversion of substrate during the circulation and to diminish the risk of damaging sensitive biological material by fluid mechanical stress. Especially animal cells fixed on a carrier matrix like hybridoma cells are very sensitive to mechanical stress (Pörtner et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Three‐dimensional numerical approach to investigate the substrate transport and conversion in an immobilized enzyme reactor

Esterl

Özmutlu²,

Hartmann³

et al. 2003

Biotech & Bioengineering

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This numerical study evaluates the momentum and mass transfer in an immobilized enzyme reactor. The simulation is based on the solution of the three-dimensional Navier-Stokes equation and a scalar transport equation with a sink term for the transport and the conversion of substrate to product. The reactor consists of a container filled with 20 spherical enzyme carriers. Each of these carriers is covered with an active enzyme layer where the conversion takes place. To account for the biochemical activity, the sink term in the scalar transport equation is represented by a standard Michaelis-Menten approach. The simulation gives detailed information of the local substrate and product concentrations with respect to external and internal transport limitations. A major focus is set on the influence of the substrate transport velocity on the catalytic process. For reactor performance analysis the overall and the local transport processes are described by a complete set of dimensionless variables. The interaction between substrate concentration, velocity, and efficiency of the process can be studied with the help of these variables. The effect of different substrate inflow concentrations on the process can be seen in relation to velocity variations. The flow field characterization of the system makes it possible to understand fluid mechanical properties and its importance to transport processes. The distribution of fluid motion through the void volume has different properties in different parts of the reactor. This phenomenon has strong effects on the arrangement of significantly different mass transport areas as well as on process effectiveness. With the given data it is also possible to detect zones of high, low, and latent enzymatic activity and to determine whether the conversion is limited due to mass transfer or reaction resistances.

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Oxygen supply for CHO cells immobilized on a packed-bed of Fibra-Cel® disks

Meuwly¹,

Loviat

Ruffieux

et al. 2006

Biotechnol. Bioeng.

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Packed-bed bioreactors (PBR) have proven to be efficient systems to culture mammalian cells at very high cell density in perfusion mode, thus leading to very high volumetric productivity. However, the immobilized cells must be continuously supplied with all nutrients in sufficient quantities to remain viable and productive over the full duration of the perfusion culture. Among all nutrients, oxygen is the most critical since it is present at very low concentration due to its low solubility in cell culture medium. This work presents the development of a model for oxygenation in a packed-bed bioreactor system. The experimental system used to develop the model was a packed-bed of Fibra-Cel disk carriers used to cultivate Chinese Hamster Ovary cells at high density ( approximately 6.1 x 10(7) cell/mL) in perfusion mode. With the help of this model, it was possible to identify if a PBR system is operated in optimal or sub-optimal conditions. Using the model, two options were proposed, which could improve the performance of the basal system by about twofold, that is, by increasing the density of immobilized cells per carrier volume from 6.1 x 10(7) to 1.2 x 10(8) cell/mL, or by increasing the packed-bed height from 0.2 to 0.4 m. Both strategies would be rather simple to test and implement in the packed-bed bioreactor system used for this study. As a result, it would be possible to achieve a substantial improvement of about twofold higher productivity as compared with the basal conditions.

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A model for oxygen supply in fixed bed reactors with immobilized hybridoma cells

Cited by 10 publications

References 29 publications

Effects of Flow Rate on Mesenchymal Stem Cell Oxygen Consumption Rates in 3D Bone-Tissue-Engineered Constructs Cultured in Perfusion Bioreactor Systems

Effects of Flow Rate on Mesenchymal Stem Cell Oxygen Consumption Rates in 3D Bone-Tissue-Engineered Constructs Cultured in Perfusion Bioreactor Systems

Three‐dimensional numerical approach to investigate the substrate transport and conversion in an immobilized enzyme reactor

Oxygen supply for CHO cells immobilized on a packed-bed of Fibra-Cel® disks

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