Effect of module geometry on the sustainable flux during microfiltration of precipitated IgG

Abstract

Recent increases in monoclonal antibody titer from Chinese Hamster Ovary cell culture has led to renewed interest in precipitation for the initial capture/purification of these high-value proteins. In this work, we examined the effect of the membrane module geometry on the sustainable flux and fouling mechanisms using human serum Immunoglobulin G (IgG) precipitated with 10 mM zinc chloride and 7 w/v % polyethylene glycol as a model system. The sustainable flux was evaluated using flux stepping experiments for both open channel cassettes and hollow fiber membrane modules. The hollow fiber modules had relatively low sustainable flux due to clogging of the fibers at the module inlet, with this behavior confirmed using both SEM imaging and hydraulic permeability data for the fouled modules. In contrast, the open channel cassettes showed no evidence of channel clogging, enabling continuous operation for at least 24 h at a filtrate flux below the experimentally determined sustainable flux. These results provide important insights into the origin of the sustainable flux during tangential flow filtration of precipitated proteins, greatly facilitating the design of precipitation-filtration processes for continuous purification of monoclonal antibody products.