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Updated: May 3, 2026

Three-Dimensionally Printed Microfluidic Cross-flow System for Ultrafiltration/Nanofiltration Membrane Performance Testing
Published on: February 13, 2016
Control of protein particle formation during ultrafiltration/diafiltration through interfacial protection
Daniel J Callahan1, Bradford Stanley, Yuling Li
1Department of Purification Process Sciences, MedImmune, Gaithersburg, Maryland, 20878.
Abstract:
This study investigates the mechanism of protein particle formation during ultrafiltration/diafiltration (UF/DF), finding that agitation drives particle formation by promoting protein-interface adsorption and desorption. Low conductivity and the presence of surfactant reduced the level of particle formation in small-scale stirring studies, and the same trends were observed in pumping and UF/DF. Polysorbate 80 (PS80) and hydroxypropyl-β-cyclodextrin (HPβCD) reduced particle formation in UF/DF by factors of 15 and 4, respectively. Measurements of conformational stability, colloidal stability, and surface tension demonstrated that PS80 protects against particle formation by preventing protein-interface adsorption, low conductivity improves the colloidal stability of the protein, and the mechanism of action of HPβCD remains unclear. This work demonstrates that interfacial adsorption-desorption of the protein during UF/DF is the principal cause of particle formation, that the level of surfactant-free particle formation depends on the colloidal stability of the protein, and that the inclusion of surfactant greatly reduces in-process particle formation during UF/DF.
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