Abstract
Pore-size distribution (PSD) is the most critical parameter for size-exclusion virus removal filters. Yet, different dry- and wet-state porometry methods yield different pore-size values. The goal of this work is to conduct comparative analysis of nitrogen gas sorption (NGSP), liquid-liquid and cryoporometry with differential scanning calorimetry (CP-DSC) methods with respect to characterization of regular and cross-linked virus removal filter paper based on cellulose nanofibers, i.e. the mille-feuille filter. The filters were further characterized with atomic force and scanning electron microscopy. Finally, the removal of the worst-case model virus, i.e. minute virus of mice (MVM; 20 nm, nonenveloped parvovirus) was evaluated. The results revealed that there is no difference of the obtained PSDs between the wet methods, i.e. DSC and liquid-liquid porometry (LLP), as well as no difference between the regular and cross-linked filters regardless of method. MVM filtration at different trans membrane pressure (TMP) revealed strong dependence of the virus removal capability on applied pressure. It was further observed that cross-linking filters showed enhanced virus removal, especially at lower TMP. In all, the results of this study highlight the complex nature of virus capture in size-exclusion filters.
Highlights
Virus removal filtration is a robust method to clear viruses and other microbial pathogens from liquids during manufacturing of protein-based pharmaceuticals and in water purification [1]
We focus on the characterization of the pore-size distribution and separation properties of a new type of nonwoven virus removal filter paper developed at Uppsala University, Sweden
The mille-feuille filter is a nonwoven wet-laid filter paper produced by hot-pressing cellulose nanofibers
Summary
Virus removal filtration is a robust method to clear viruses and other microbial pathogens from liquids during manufacturing of protein-based pharmaceuticals and in water purification [1]. The first virus removal filters, which were based on graded nitrocellulose membranes, were developed by Elford in the 1930s [2,3,4,5,6,7]. Already it was recognized that virus removal filtration is a complex process which can involve several simultaneous mechanisms, i.e. size exclusion (sieving), entrapment (depth filtration), interception (electrostatic or hydrophobic adsorption), and blockage (aggregation due to colloidal instability). Most of the virus removal filters are not isoporous and have a certain pore-size distribution, sometimes done deliberately in order to enhance the flux across the filter. Virus breakthrough may potentially occur even when the nominal
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