Computational fluid dynamics simulation improves the design and characterization of a plug-flow-type scale-down...

Area of Science:

• Biotechnology
• Biochemical Engineering
• Process Intensification

Background:

• Bioprocess scale-up is a significant challenge in biotechnology, hindering efficient production.
• Scale-down bioreactors and computational fluid dynamics (CFD) are crucial for studying large-scale process variations in the lab.
• Understanding fluid dynamics and mixing is key to optimizing bioreactor performance.

Purpose of the Study:

• To design and characterize a novel, flexible scale-down bioreactor setup.
• To use CFD simulations to establish scale-down criteria based on mixing times.
• To evaluate the setup's performance in high-cell-density Escherichia coli cultivations for producing antigen-binding fragments (Fab).

Main Methods:

• Rational design and comprehensive characterization of a modular plug-flow reactor connected to a stirred-tank bioreactor.
• Computational fluid dynamics (CFD) simulations utilizing realizable k-ε and SST k-ω turbulence models.
• Experimental verification of CFD models and scale-down cultivation of Escherichia coli for Fab production.

Main Results:

• CFD analysis determined mixing time differences between 20 L and 4000 L bioreactors, establishing a scale-down criterion.
• The scale-down setup demonstrated feasibility for high-cell-density Escherichia coli cultivations.
• Cultivations in the scale-down setup resulted in an 11% reduction in biomass yield and a 20% reduction in specific product yield, with an increased intracellular Fab fraction.

Conclusions:

• The flexible scale-down bioreactor setup, integrated with CFD, is a valuable tool for investigating scale effects in bioprocesses.
• The setup aids in understanding heterogeneities and optimizing laboratory-scale experiments for improved bioprocess scale-up.
• Further large-scale data is needed to refine the setup and accelerate future bioprocess scale-up.