The Hydrodynamics of Micro-particle Slurries in Hollow Fiber Membranes
Open Access
- Author:
- Long, Matthew Ray
- Area of Honors:
- Chemical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Andrew Zydney, Thesis Supervisor
Darrell Velegol, Thesis Honors Advisor - Keywords:
- hydrodynamics
slurry
hollow fiber membrane
critical flux - Abstract:
- Downstream processing is a significant bottleneck in the production of protein-based pharmaceuticals and accounts for a large fraction of manufacturing costs. Countercurrent tangential flow chromatography (CTC) has been proposed as an alternative to traditional column chromatography with increased throughput and lower cost. In the CTC system, a concentrated slurry of resin particles flow through a series of static mixers and hollow fiber membrane modules in a countercurrent arrangement, with binding, washing, and elution performed sequentially. Initial studies have demonstrated the feasibility of this process, with the individual modules operated below the critical flux to insure stable filtration without fouling. The overall objective of this thesis was to develop a more comprehensive and fundamental understanding of the hydrodynamic behavior of concentrated resin slurry particles in hollow fiber membranes. The critical flux was evaluated for a variety of resin particles, ranging in size from 10 to 45 µm, over a range of cross flow velocities, particle concentrations, and in different buffer solutions. Experimental data indicate that the critical flux (J_CRIT) varies linearly with the wall shear stress (τ_w) over a wide range of conditions. The ratio of J_CRIT/τ_w was thus used as a fundamental parameter to describe the critical flux for a given particle and feed concentration. J_CRIT decreased with increasing feed particle volume fraction and was essentially independent of the buffer condition and particle size. The critical flux data were analyzed using the Brownian diffusion, shear-induced diffusion, and inertial lift models. The linear dependence on the wall shear stress is in agreement with the form predicted by the shear-induced diffusion model, but this model was unable to explain the observed dependence on particle size and concentration. Instead, it appears that the critical flux is determined by a critical (maximum) value of outlet particle concentration, which was equal to about 40% of the dense packed concentration. These results provide important insights into the hydrodynamic conditions needed for stable operation of the hollow fiber membrane modules employed in countercurrent tangential chromatography systems.