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Protein fouling can significantly reduce the filtrate flux, capacity, and virus retention during processing of plasma- or mammalian cell-derived biopharmaceuticals through virus removal filters. We use focused ion beam (FIB) milling and scanning electron microscopy (SEM) to directly evaluate changes in 3D pore structure in a Viresolve® Pro membrane due to fouling by human serum immunoglobulin G. Protein fouling causes a significant reduction in the membrane porosity, which decreases by approximately 40% in the size-selective region near the exit of the highly asymmetric Viresolve® Pro membrane after the filter is fouled to 90% flux decline. There is a corresponding reduction in the number of small pores by more than a factor of two. Model simulations of flow and particle transport in the protein-fouled membrane are in good agreement with independent experimental measurements of the permeability and location of particle capture. Simulations show an upstream shift in the location of nanoparticle capture (away from the filter exit) by about 0.4 µm for the membrane fouled to 90% flux decline. This is due to pore constriction from protein deposition, highlighting how fouling redistributes flow paths within the membrane. These results demonstrate the capability of using FIB-SEM to directly evaluate the effects of protein fouling on the 3D pore structure in virus removal filters, providing important insights into how protein fouling alters the performance of these highly selective membranes.more » « lessFree, publicly-accessible full text available December 1, 2026
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Brickey, Kaitlyn P.; Zydney, Andrew L.; Gomez, Enrique D. (, Journal of Membrane Science)
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Culp, Tyler E.; Khara, Biswajit; Brickey, Kaitlyn P.; Geitner, Michael; Zimudzi, Tawanda J.; Wilbur, Jeffrey D.; Jons, Steven D.; Roy, Abhishek; Paul, Mou; Ganapathysubramanian, Baskar; et al (, Science)Biological membranes can achieve remarkably high permeabilities, while maintaining ideal selectivities, by relying on well-defined internal nanoscale structures in the form of membrane proteins. Here, we apply such design strategies to desalination membranes. A series of polyamide desalination membranes—which were synthesized in an industrial-scale manufacturing line and varied in processing conditions but retained similar chemical compositions—show increasing water permeability and active layer thickness with constant sodium chloride selectivity. Transmission electron microscopy measurements enabled us to determine nanoscale three-dimensional polyamide density maps and predict water permeability with zero adjustable parameters. Density fluctuations are detrimental to water transport, which makes systematic control over nanoscale polyamide inhomogeneity a key route to maximizing water permeability without sacrificing salt selectivity in desalination membranes.more » « less
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