CFD based mass transfer modeling of a single use bioreactor for production of monoclonal antibody biotherapeutics

Mishra, Somesh; Kumar, Vikash; Sarkar, Jayati; Rathore, Anurag S.

doi:10.1016/j.cej.2021.128592

Cited by 32 publications

(27 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The bag is placed in a solid, cylindrical outer shell to which it is deemed to perfectly conform to and accordingly, a cylindrical vessel shape is considered in simulations. This is in contrast to the recent study by Mishra et al [ 10 ], where a hexagonal cross-section is used for the same XDR-10 bioreactor. The impeller has three pitched blades, angled at 40, see Figure 1 a, and the impeller diameter

is 13.6 cm.…”

Section: Methodsmentioning

confidence: 75%

“…Mishra et al [ 10 ] investigated the XDR-10; they considered the bubble size distribution and studied the volumetric oxygen mass transfer coefficient for the 20

m sparger. The present study concerns the microporous spargers with focus on the 2

m pore size since they lead to a higher oxygen mass transfer compared to the 20

m size.…”

Section: Introductionmentioning

confidence: 99%

“…The present study concerns the microporous spargers with focus on the 2

m pore size since they lead to a higher oxygen mass transfer compared to the 20

m size. Mishra et al [ 10 ] used empirical correlations to determine the mixing time and not with a detailed computational simulation. In the present study, Euler–Lagrange simulations are performed with the commercial software MixIT [ 11 ], which is commonly used for the characterization of industrial stirred tank reactors and for which only one-way coupling is available.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10

et al. 2022

View full text Add to dashboard Cite

Understanding the hydrodynamic conditions in bioreactors is of utmost importance for the selection of operating conditions during cell culture process development. In the present study, the two-phase flow in the lab-scale single-use bioreactor XcellerexTM XDR-10 is characterized for working volumes from 4.5 L to 10 L, impeller speeds from 40 rpm to 360 rpm, and sparging with two different microporous spargers at rates from 0.02 L min−1 to 0.5 L min−1. The numerical simulations are performed with the one-way coupled Euler–Lagrange and the Euler–Euler models. The results of the agitated liquid height, the mixing time, and the volumetric oxygen mass transfer coefficient are compared to experiments. For the unbaffled XDR-10, strong surface vortex formation is found for the maximum impeller speed. To support the selection of suitable impeller speeds for cell cultivation, the surface vortex formation, the average turbulence energy dissipation rate, the hydrodynamic stress, and the mixing time are analyzed and discussed. Surface vortex formation is observed for the maximum impeller speed. Mixing times are below 30 s across all conditions, and volumetric oxygen mass transfer coefficients of up to 22.1 h−1 are found. The XDR-10 provides hydrodynamic conditions which are well suited for the cultivation of animal cells, despite the unusual design of a single bottom-mounted impeller and an unbaffled cultivation bioreactor.

show abstract

is 13.6 cm.…”

Section: Methodsmentioning

confidence: 75%

“…Mishra et al [ 10 ] investigated the XDR-10; they considered the bubble size distribution and studied the volumetric oxygen mass transfer coefficient for the 20

m sparger. The present study concerns the microporous spargers with focus on the 2

m pore size since they lead to a higher oxygen mass transfer compared to the 20

m size.…”

Section: Introductionmentioning

confidence: 99%

“…The present study concerns the microporous spargers with focus on the 2

m pore size since they lead to a higher oxygen mass transfer compared to the 20

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The most commonly used bioreactors in both process development and commercial production are stirred bioreactors with forced aeration. Both computational fluid dynamics (CFD) and classical process engineering approaches are used for optimization and scaling-up of stirred bioreactor processes [3][4][5][6]. CFD is based on the laws of conservation of energy, mass, and momentum.…”

Section: Introductionmentioning

confidence: 99%

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

Seidel

Eibl

2021

Processes

View full text Add to dashboard Cite

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.

show abstract

“…For industrially relevant macro‐scale CFD modeling, the Eulerian multifluid framework is most often used to simulate the continuous phase, the dispersed phase, and their interactions in bioreactors (Deen et al, 2002; Khopkar et al, 2005; Laakkonen et al, 2006). The level of details in modeling the dispersed phase could vary from the use of constant bubble diameter (Gakingo et al, 2020; Rzehak & Krepper, 2016), to a simplified bubble number density (BND) equation (Bakker, 1992; Lane et al, 2005), or to more complex population balance modeling (Amer et al, 2019; Gimbun et al, 2009; Kerdouss et al, 2008; Mishra et al, 2021; Ranganathan & Sivaraman, 2011; Scully et al, 2020). Single‐phase modeling has also been used to investigate mixing time in high solids anaerobic digestion using different impeller types (Wu, 2012) or for optimization of sparger design in a pilot‐scale photobioreactor when coupled with a first‐order kinetic method (Ali et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Towards enhancement of gas–liquid mass transfer in bioelectrochemical systems: Validation of a robust CFD model

Karimi

Widén

Nygård

et al. 2021

Biotech & Bioengineering

View full text Add to dashboard Cite

Mass transfer has been identified as a major bottleneck in gas fermentation and microbial conversion of carbon dioxide to chemicals. We present a pragmatic and validated Computational Fluid Dynamics (CFD) model for mass transfer in bioelectrochemical systems. Experiments were conducted to measure mixing times and mass transfer in a Duran bottle and an H‐cell. An Eulerian–Eulerian framework with a simplified model for the bubble size distribution (BSD) was developed that utilized only one additional equation for the bubble number density while including the breakup and coalescence. Validations of the CFD model for mixing times showed that the predictions were within the confidence intervals of the measurements, verifying the model's capability in simulating the hydrodynamics. Further validations were performed using constant and varying bubble diameters for the mass transfer. The results showed the benefits of a simplified BSD model, as it yielded improvements of seven and four times in accuracy when assessed against the experimental data for the Duran bottle and H‐cell, respectively. Modeling of the H‐cell predicted that a lower stirring rate improves mass transfer compared with higher stirring rates, which is of great importance when designing microbial cultivation processes. The model offers a feasible framework for advanced modeling of gas fermentation and microbial electrosynthesis.

show abstract

CFD based mass transfer modeling of a single use bioreactor for production of monoclonal antibody biotherapeutics

Cited by 32 publications

References 43 publications

CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10

CFD-Based and Experimental Hydrodynamic Characterization of the Single-Use Bioreactor XcellerexTM XDR-10

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

Towards enhancement of gas–liquid mass transfer in bioelectrochemical systems: Validation of a robust CFD model

Contact Info

Product

Resources

About