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Optimization of stirred animal cell bioreactor based on CFD-PBM

  • Xuemin Wang EMAIL logo und Benchi Ma
Veröffentlicht/Copyright: 18. Februar 2025
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Abstract

Stirred bioreactor has been widely used in biopharmaceutical field, and it is particularly important to understand the culture environment of animal cells in stirred bioreactor. This study, utilizing Computational Fluid Dynamics (CFD) in conjunction with the Population Balance Model (PBM), explores the effect of various operational conditions and impeller combinations (downward-pumping elephant ear impeller (EED) combined with a concave disc turbine impeller (CBDT), dual downward-pumping elephant ear impellers (EED-EED), and a combination of downward-pumping (EED) and upward-pumping (EEU) elephant ear impellers) on bioreactor performance, with the goal of developing a stirred bioreactor suited for animal cell culture. The findings reveal that increasing the stirring rate significantly enhances fluid circulation within the bioreactor, leading to an increase in gas holdup. Enhanced stirring rate and aeration not only facilitate bubble dispersion but also result in a significantly higher gas holdup in the lower part of the bioreactor compared to the upper part. Moreover, higher stirring rate also lead to larger bubble diameters. At the highest stirring rate, the maximum hydrodynamic stress in the bioreactor reaches 16 Pa, while the Kolmogorov length scale is smaller at high stirring rate. The EED-EEU demonstrates effective gas dispersion with uniform bubble distribution and minimal hydrodynamic stress; the EED-EED combination, while offering the best bubble dispersion, is associated with larger bubble diameters and higher hydrodynamic stress.


Corresponding author: Xuemin Wang, School of Mechanical Engineering, Shanghai Institute of Technology, 201418 Shanghai, China; and Jiangsu Key Laboratory of Advanced Food Manufacturing Equipment & Technology, 214122 Wuxi, China, E-mail:

Funding source: Jiangsu Province Food Advanced Manufacturing Equipment Technology Key laboratory open project funding

Award Identifier / Grant number: FM-2023-03

Acknowledgment

This work was supported from the Jiangsu Province Food Advanced Manufacturing Equipment Technology Key laboratory open project funding FM-2023-03.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: Xuemin Wang: Writing – review and editing, funding acquisition, project administration, resources. Benchi Ma: Writing – original draft, methodology, conceptualization. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  6. Research funding: None declared.

  7. Data availability: Data will be made available on request.

Nomenclature

ρ i

Density (kg/m3)

α i

Volume fraction (dimensionless)

v i

Velocity vector (m/s)

g

Gravitational constant (m/s2)

i

Phase: gas/liquid

P

Pressure (Pa)

Re

Reynolds number

μ i,eff

Effective viscosity of phase i (Pa s)

K la

Overall mass transfer coefficient, h−1

We ij

Weber number

F lg

Interfacial force due to drag (N m3)

d g

Bubble diameter (mm)

C D

Drag coefficient

k

Turbulent kinetic energy (J/kg)

ε

Turbulent energy dissipation rate (m2/s3)

Y M

Energy due to the oscillating values of compressible turbulence to overall dissipation rate

G b

Turbulent kinetic energy generated due to buoyancy

G k

Turbulent kinetic energy generated due to mean velocity gradient

S B

Source term caused by bubble breakup

S D

Source term caused by bubble coalescence

ϖ c

Collision frequency

P c

Coalescence efficiency

d 32

Sauter mean diameter (mm)

α g

Gas volume fraction

μ

Viscosity (Pa s)

ξ

The size ratio between two bubbles

a

Interfacial area (m2/m3)

τ

Hydrodynamic stress (Pa)

λ

Kolmogorov length scale (μm)

v

Kinematic viscosity ((m2)/s)

l

Liquid phase

s

Solid phase

σ

Asymptotic ratio

Abbreviations

CFD

Computational fluid dynamics

PBM

Population balance model

CARPT

Computer-automated radioactive particle tracking

CT

Computed tomography

PIV

Particle image velocimetry

CHO

Chinese hamster ovary

rpm

Revolutions per minute

VVm

Volume per volume per minute

MRF

Moving reference frame

EED

Elephant ear down impeller

EEU

Elephant ear up impeller

CBDT

Concave disc turbine impeller

GCI

Grid convergence index

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Received: 2024-09-25
Accepted: 2025-01-31
Published Online: 2025-02-18

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