Document Type

Article

Publication Date

5-2025

Keywords

Bioseparations, Virus filter, Modeling, Multilayer membrane structure, Pore size distribution

Abstract

Robust virus reduction and high permeability are characteristic properties of virus filters, which are modeled as having an asymmetric multilayer membrane structure with a pore size distribution. In this study, an advanced heterogeneous multilayer model for the multicomponent solution containing viruses, protein monomers and aggregates, has been developed to reproduce the filtration behavior, virus reduction, and virus/protein retention distribution in the virus filter with asymmetric membrane structure. Calculations based on the multilayer membrane structure with consideration of the effect of aggregate size and concentration numerically reproduce the experimental results that virus LRV (log reduction value) decreases when a large number of protein aggregates close in size to that of virus are present in the solution and that high virus LRV can be achieved even when the permeability is significantly reduced by the filtration of high concentration protein solution. In addition, the model calculation reproduced the filtration behavior of both constant flux and constant pressure filtrations with the same physical parameters, suggesting the equivalence of both filtration control modes. The advanced multilayer model was well able to reproduce filtration behavior, virus LRV and virus/protein retention distribution in the membrane by the same physical parameters at 1 mg/mL IgG. However, at 10 mg/mL IgG, while filtration behavior and virus LRV could also be reproduced, the virus/protein retention distribution in the membrane could not be well reproduced. This may simply indicate the possibility that larger sized aggregates that do not follow the size exclusion mechanism may be present in the concentrated feed solution.

Comments

Web of Science

Elsevier

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