A CFD-Based Digital Framework for Scaling Optimization of Orbital Rocking Bioreactors

Area of Science:

• Biotechnology
• Chemical Engineering
• Process Development

Background:

• Bioreactor scale-up is critical for consistent cell culture performance.
• Hydrodynamic similarity across scales is essential for robust bioprocesses.
• Orbital rocking bioreactors offer unique advantages but require optimized scale-up strategies.

Purpose of the Study:

• To develop and validate a computational fluid dynamics (CFD)-guided digital framework for optimizing the scale-up of the CELBIC orbital rocking bioreactor.
• To ensure hydrodynamic similarity between the CELBIC5 and CELBIC50 systems.
• To establish a systematic strategy for digital process development in single-use bioreactors.

Main Methods:

• Utilized lattice Boltzmann-based CFD simulations to evaluate hydrodynamic parameters (velocity, shear stress, energy dissipation rate).
• Developed a root mean square error (RMSE)-based method to quantify hydrodynamic similarity across scaled conditions.
• Employed response surface analysis to refine the optimized scale-up parameters.

Main Results:

• Identified an optimized scale-up condition (10 L, 7°, 19 rpm) for the CELBIC50 bioreactor relative to the CELBIC5 reference (1 L, 6°, 30 rpm).
• The optimized condition demonstrated the lowest combined RMSE, indicating substantial hydrodynamic equivalence.
• The digital framework successfully enabled rational scale-up, ensuring process consistency.

Conclusions:

• Integrating CFD and RMSE-based analyses provides a rational and systematic approach for orbital rocking bioreactor scale-up.
• The developed digital framework facilitates efficient process development and optimization for single-use bioreactor systems.
• This methodology ensures hydrodynamic similarity, crucial for maintaining cell culture performance during scale-up.