Scale-up of controlled-shear affinity filtration using computational fluid dynamics.

Area of Science:

• Bioprocess Engineering
• Separation Science
• Computational Fluid Dynamics

Background:

• Controlled shear affinity filtration (CSAF) integrates rotor technology with membrane affinity chromatography.
• CSAF facilitates direct capture and purification of secreted proteins from cell culture.
• Previous studies utilized laboratory-scale CSAF units.

Purpose of the Study:

• To extend computational fluid dynamics (CFD) simulations to larger-scale CSAF devices (up to 140 cm rotor radius).
• To investigate fluid hydrodynamics and filter performance in scaled-up CSAF units.
• To design and optimize a preparative CSAF device for industrial bioprocessing.

Main Methods:

• Computational fluid dynamics (CFD) simulations were employed to model fluid hydrodynamics.
• Analysis of complex flow patterns, including turbulent boundary layers, in large-scale CSAF units.
• In silico design and optimization of a preparative CSAF device.

Main Results:

• Complex fluid hydrodynamics, including turbulent boundary layers, were identified in larger-scale CSAF units.
• CFD simulations are crucial for reliable CSAF scale-up.
• An in silico designed preparative CSAF device with a 140 cm rotor radius and 5.93 m² filtration area was developed.
• The scaled-up device can process 1000 L of cell culture in approximately 2 hours.
• A novel parallelization method for CSAF units was proposed for larger bioprocessing volumes.

Conclusions:

• CFD is essential for the successful scale-up of CSAF technology.
• The designed preparative CSAF device is suitable for industrial-scale protein purification.
• The proposed parallelization strategy enhances CSAF applicability for very large bioprocessing operations.