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Strategies for Tailoring the Pore-Size Distribution of Virus Retention Filter Papers
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. (Nanotechology and Functional Materials)
2016 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 8, no 22, p. 13759-13767Article in journal (Refereed) Published
Abstract [en]

The goal of this work is to demonstrate how the pore-size distribution of the nanocellulose-based virus-retentive filter can be tailored. The filter paper was produced using cellulose nanofibers derived from Cladophora sp. green algae using the hot-press drying at varying drying temperatures. The produced filters were characterized using scanning electron microscopy, atomic force microscopy, and N2 gas sorption analysis. Further, hydraulic permeability and retention efficiency toward surrogate 20 nm model particles (fluorescent carboxylate-modified polystyrene spheres) were assessed. It was shown that by controlling the rate of water evaporation during hot-press drying the pore-size distribution can be precisely tailored in the region between 10 and 25 nm. The mechanism of pore formation and critical parameters are discussed in detail. The results are highly valuable for development of advanced separation media, especially for virus-retentive size-exclusion filtration.

Place, publisher, year, edition, pages
Uppsala, 2016. Vol. 8, no 22, p. 13759-13767
Keywords [en]
virus-retentive filtration; nanocellulose; paper making; size-exclusion filtration; Cladophora cellulose; hydraulic permeability
National Category
Nano Technology
Identifiers
URN: urn:nbn:se:uu:diva-294387DOI: 10.1021/acsami.6b03093ISI: 000377642100012PubMedID: 27144657OAI: oai:DiVA.org:uu-294387DiVA, id: diva2:929719
Funder
Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist ByggmästareAvailable from: 2016-05-19 Created: 2016-05-19 Last updated: 2018-10-24Bibliographically approved
In thesis
1. Mille-feuille Filter: A Non-woven Nano-cellulose Based Virus Removal Filter for Bioprocessing
Open this publication in new window or tab >>Mille-feuille Filter: A Non-woven Nano-cellulose Based Virus Removal Filter for Bioprocessing
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Virus removal filters, produced from synthetic surface-modified polymers or regenerated cellulose by phase inversion, are vital to the production of therapeutic proteins such as monoclonal antibodies and plasma proteins. Use of these filters is also one of the most expensive purification steps in the downstream processing of proteins due to high sales price and being limited to a single use.

In this thesis, a virus removal filter produced from Cladophora sp. algal nanocellulose has been characterized. The mille-feuille (‘‘a thousand leaves’’) filter paper is the first non-woven, wet-laid filter paper composed of 100% native nanocellulose that is capable of removing the ‘‘worst-case’’ model viruses, the non-enveloped parvoviruses, i.e., minute virus of mice (MVM; 18–20 nm), from water with a log10 reduction value (LRV) ≥5.78 (≥99.9998%). The mille-feuille filter features a unique internal stratified architecture that is the result of nanofiber self-assembly into 2D nanosheets during manufacturing. Such an internal structure has several benefits for achieving highly selective virus removal with high flux.

The pore size distribution can be tailored to sizes from 10 to 25 nm by altering drying conditions, i.e. temperature and drying rate; therefore, the filter can be customized to target the size cut-off of the smallest virus particles known. The mille-feuille filter has achieved up to 200 L m-2 h-1 (LMH) bar-1 in flux. Furthermore, protein recovery rates of 99% were measured during bovine serum albumin (BSA) filtration. Protein recovery was determined to be dependent on the protein size and charge.

Filtration of cell culture media was also investigated, and no fouling was observed with fluxes of 400 LMH for an 11 µm filter and 140 LMH for a 33 µm filter at 3 bar. An LRV of >4.8 was measured for the 33 µm filter at 3 bar, but only 2.2 was measured for the 11 µm filter at 3 bar using the small-size ФX174 bacteriophage as a model virus.

Furthermore, the virus reduction was discovered to be pressure dependent, with the LRV increasing with trans membrane pressure (TMP). The tendency to virus breakthrough was partly mitigated at low TMPs by filter cross-linking.

In summary, the mille-feuille filter paper has the characteristics to be a promising virus removal filter for both upstream and downstream applications. Further studies shall focus on the area of protein filtration to gain a better understanding of how buffer conditions and the physical characteristics of proteins contribute to filter fouling.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 70
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1738
Keywords
virus filtration, mille-feuille, downstream, nanocellulose, protein throughput, protein recovery, LRV, MVM, Cladophora, non-woven filter
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-364082 (URN)978-91-513-0489-2 (ISBN)
Public defence
2018-12-14, Polhemsalen, 10134, Ångström, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2018-11-20 Created: 2018-10-24 Last updated: 2018-11-30

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Gustafsson, SimonMihranyan, Albert

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