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  • 1.
    Basu, Alex
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Tummala, Gopi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Heitz, Karen
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strietzel, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Yang, Jiaojiao
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Notfors, Celina
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Wang, Huan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Miljövänliga nanomaterial från växtriket tillåter gröna alternative för framtiden2017In: SciFest 2017 / [ed] Uppsala Universitet, 2017Conference paper (Other academic)
  • 2.
    Gustafsson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Manukyan, Levon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Significance of Brownian Motion for Nanoparticle and Virus Capture in Nanocellulose-Based Filter Paper2018In: Membranes, ISSN 2077-0375, E-ISSN 2077-0375, Vol. 8, no 4, article id 90Article in journal (Refereed)
    Abstract [en]

    Pressure-dependent breakthrough of nanobioparticles in filtration was observed and it was related to depend on both convective forces due to flow and diffusion as a result of Brownian motion. The aim of this work was to investigate the significance of Brownian motion on nanoparticle and virus capture in a nanocellulose-based virus removal filter paper through theoretical modeling and filtration experiments. Local flow velocities in the pores of the filter paper were modeled through two different approaches (i.e., with the Hagen–Poiseuille equation) and by evaluating the superficial linear flow velocity through the filter. Simulations by solving the Langevin equation for 5 nm gold particles and 28 nm ΦX174 bacteriophages showed that hydrodynamic constraint is favored for larger particles. Filtration of gold nanoparticles showed no difference in retention for the investigated fluxes, as predicted by the modeling of local flow velocities. Filtration of ΦX174 bacteriophages exhibited a higher retention at higher filtration pressure, which was predicted to some extent by the Hagen–Poiseuille equation but not by evaluation of the superficial linear velocity. In all, the hydrodynamic theory was shown able to explain some of the observations during filtration.

  • 3.
    Gustafsson, Olof
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Manukyan, Levon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Tummala, Gopi Krishna
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Zaman, Sharmin
    Univ Dhaka, CARS, Dhaka 1000, Bangladesh.
    Begum, Anowara
    Univ Dhaka, Dept Microbiol, Sci Complex, Dhaka 1000, Bangladesh.
    Alfasane, Md. Almujaddade
    Univ Dhaka, Dept Bot, Curzon Hall Campus, Dhaka 1000, Bangladesh.
    Siddique-e-Rabbani, Khondkar
    Univ Dhaka, Dept Biomed Phys & Technol, Curzon Hall Bldg, Dhaka 1000, Bangladesh.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Scalable and Sustainable Total Pathogen Removal Filter Paper for Point-of-Use Drinking Water Purification in Bangladesh2019In: ACS SUSTAINABLE CHEMISTRY & ENGINEERING, ISSN 2168-0485, Vol. 7, no 17, p. 14373-14383Article in journal (Refereed)
    Abstract [en]

    This article describes for the first time the full cycle of development from raw material cultivation to real-life application of a truly sustainable and scalable filter paper material intended for point-of-use drinking water purification in Bangladesh. The filter paper, featuring tailored pathogen removal properties, is produced from nanocellulose extracted from Pithophora green macroalgae, growing locally in Bangladesh, a new unexploited resource that can address a global problem. We demonstrate that the Pithophora cellulose filter paper can be used as a total pathogen barrier to remove all types of infectious viruses and bacteria from water. The performance of the filter is validated using surrogate latex nanobeads, in vitro model viruses, and real-life water samples collected from the Turag River and Dhanmondi Lake in Dhaka, Bangladesh. Access to clean drinking water is a persistent problem in Bangladesh, affecting tens of millions of people every day. The mortality rate due to water-borne diarreal infections, including viral infections, among susceptible population groups, especially among children under age of 5, is still very high. The proposed solution can dramatically improve the quality of lives for millions of people in the entire Southeast Asian region including and beyond the borders of Bangladesh.

  • 4.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mille-feuille Filter: A Non-woven Nano-cellulose Based Virus Removal Filter for Bioprocessing2018Doctoral 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.

    List of papers
    1. Mille-feuille paper: a novel type of filter architecture for advanced virus separation applications
    Open this publication in new window or tab >>Mille-feuille paper: a novel type of filter architecture for advanced virus separation applications
    Show others...
    2016 (English)In: Materials Horizons, ISSN 2051-6347, E-ISSN 2051-6355, Vol. 3, no 4, p. 320-327Article in journal (Refereed) Published
    Abstract [en]

    Mille-feuille (“a thousand leaves”) paper is the first non-woven, wet-laid filter paper, composed of 100% native cellulose, which is capable of removal of the “worst-case” model virus, the non-enveloped parvoviruses, i.e. minute virus of mice (MVM; 18–20 nm), from water with a log10 reduction value (LRV) >5 (>99.999%). We further illustrate how the flow rate across the mille-feuille paper can be increased exponentially so that flux rates in the order of 350 L m−2 h−1 bar−1 can be potentially achieved.

    Place, publisher, year, edition, pages
    Uppsala: , 2016
    National Category
    Nano Technology
    Identifiers
    urn:nbn:se:uu:diva-294389 (URN)10.1039/C6MH00090H (DOI)000378716500007 ()
    Funder
    Knut and Alice Wallenberg Foundation
    Available from: 2016-05-19 Created: 2016-05-19 Last updated: 2018-10-24Bibliographically approved
    2. Characterization of Regular and Cross-linked Virus Removal Filter Papers: Comparative Analysis of Dry and Wet Porometry Methods and Virus Removal Properties
    Open this publication in new window or tab >>Characterization of Regular and Cross-linked Virus Removal Filter Papers: Comparative Analysis of Dry and Wet Porometry Methods and Virus Removal Properties
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Nano Technology
    Identifiers
    urn:nbn:se:uu:diva-363986 (URN)
    Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-10-24
    3. Strategies for Tailoring the Pore-Size Distribution of Virus Retention Filter Papers
    Open this publication in new window or tab >>Strategies for Tailoring the Pore-Size Distribution of Virus Retention Filter Papers
    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
    Keywords
    virus-retentive filtration; nanocellulose; paper making; size-exclusion filtration; Cladophora cellulose; hydraulic permeability
    National Category
    Nano Technology
    Identifiers
    urn:nbn:se:uu:diva-294387 (URN)10.1021/acsami.6b03093 (DOI)000377642100012 ()27144657 (PubMedID)
    Funder
    Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist Byggmästare
    Available from: 2016-05-19 Created: 2016-05-19 Last updated: 2018-10-24Bibliographically approved
    4. Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications
    Open this publication in new window or tab >>Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications
    2017 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 33, no 19, p. 4729-4736Article in journal (Refereed) Published
    Abstract [en]

    Protein-based pharmaceutics are widely explored for healthcare applications, and 6 out of 10 best-selling drugs today are biologicals. The goal of this work was to evaluate the protein nanocellulose interactions in paper filter for advanced separation applications such as virus removal filtration and bioprocessing. The protein recovery was measured for bovine serum albumin (BSA), gamma-globulin, and lysozyme using biuret total protein reagent and polyacrylamide gel electrophoresis (PAGE), and the throughput was characterized in terms of flux values from fixed volume filtrations at various protein concentrations and under worst case experimental conditions. The affinity of cellulose to bind various proteins, such as BSA, lysozyme, gamma-globulin, and human IgG was quantified using a quartz crystal microbalance (QCMB) by developing a new method of fixing the cellulose fibers to the electrode surface without cellulose dissolution-precipitation. It was shown that the. mille-feuille filter exhibits high protein recovery, that is, similar to 99% for both BSA and lysozyme. However, gamma-globulin does not pass through the membrane due to its large size (i.e., >180 kDa). The PAGE data show no substantial change in the amount of dimers and trimers before and after filtration. QCMB analysis suggests a low affinity between the nanocellulose surface and proteins. The nanocellulose-based filter exhibits desirable inertness as a filtering material intended for protein purification.

    Place, publisher, year, edition, pages
    AMER CHEMICAL SOC, 2017
    National Category
    Nano Technology
    Research subject
    Engineering Science with specialization in Nanotechnology and Functional Materials
    Identifiers
    urn:nbn:se:uu:diva-326244 (URN)10.1021/acs.langmuir.7b00566 (DOI)000401674900015 ()28441870 (PubMedID)
    Funder
    Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist Byggmästare
    Available from: 2017-08-10 Created: 2017-08-10 Last updated: 2018-10-24
    5. Significance of Brownian Motion for Nanoparticle and Virus Capture in Nanocellulose-Based Filter Paper
    Open this publication in new window or tab >>Significance of Brownian Motion for Nanoparticle and Virus Capture in Nanocellulose-Based Filter Paper
    2018 (English)In: Membranes, ISSN 2077-0375, E-ISSN 2077-0375, Vol. 8, no 4, article id 90Article in journal (Refereed) Published
    Abstract [en]

    Pressure-dependent breakthrough of nanobioparticles in filtration was observed and it was related to depend on both convective forces due to flow and diffusion as a result of Brownian motion. The aim of this work was to investigate the significance of Brownian motion on nanoparticle and virus capture in a nanocellulose-based virus removal filter paper through theoretical modeling and filtration experiments. Local flow velocities in the pores of the filter paper were modeled through two different approaches (i.e., with the Hagen–Poiseuille equation) and by evaluating the superficial linear flow velocity through the filter. Simulations by solving the Langevin equation for 5 nm gold particles and 28 nm ΦX174 bacteriophages showed that hydrodynamic constraint is favored for larger particles. Filtration of gold nanoparticles showed no difference in retention for the investigated fluxes, as predicted by the modeling of local flow velocities. Filtration of ΦX174 bacteriophages exhibited a higher retention at higher filtration pressure, which was predicted to some extent by the Hagen–Poiseuille equation but not by evaluation of the superficial linear velocity. In all, the hydrodynamic theory was shown able to explain some of the observations during filtration.

    National Category
    Nano Technology
    Identifiers
    urn:nbn:se:uu:diva-362868 (URN)10.3390/membranes8040090 (DOI)000455071400005 ()30301138 (PubMedID)
    Funder
    Knut and Alice Wallenberg FoundationStiftelsen Olle Engkvist ByggmästareSwedish Research Council
    Available from: 2018-10-11 Created: 2018-10-11 Last updated: 2020-01-29Bibliographically approved
    6. Growth Media Filtration Using Nanocellulose-based Virus Removal Filter for Upstream Biopharmaceutical Processing
    Open this publication in new window or tab >>Growth Media Filtration Using Nanocellulose-based Virus Removal Filter for Upstream Biopharmaceutical Processing
    2018 (English)In: Journal of Membrane Science, ISSN 0376-7388, E-ISSN 1873-3123Article in journal (Other academic) Published
    National Category
    Nano Technology
    Identifiers
    urn:nbn:se:uu:diva-363987 (URN)
    Available from: 2018-10-22 Created: 2018-10-22 Last updated: 2018-11-16
  • 5.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Nanocellulose Membranes for virus removal, pore-size dependence on the drying condition during manufacturing2015Conference paper (Refereed)
  • 6.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala Universitet.
    Lordat, Pascal
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hanrieder, Tobias
    Asper, Marcel
    Schaefer, Oliver
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mille-feuille paper: a novel type of filter architecture for advanced virus separation applications2016In: Materials Horizons, ISSN 2051-6347, E-ISSN 2051-6355, Vol. 3, no 4, p. 320-327Article in journal (Refereed)
    Abstract [en]

    Mille-feuille (“a thousand leaves”) paper is the first non-woven, wet-laid filter paper, composed of 100% native cellulose, which is capable of removal of the “worst-case” model virus, the non-enveloped parvoviruses, i.e. minute virus of mice (MVM; 18–20 nm), from water with a log10 reduction value (LRV) >5 (>99.999%). We further illustrate how the flow rate across the mille-feuille paper can be increased exponentially so that flux rates in the order of 350 L m−2 h−1 bar−1 can be potentially achieved.

  • 7.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Manukyan, Levon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications2017In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 33, no 19, p. 4729-4736Article in journal (Refereed)
    Abstract [en]

    Protein-based pharmaceutics are widely explored for healthcare applications, and 6 out of 10 best-selling drugs today are biologicals. The goal of this work was to evaluate the protein nanocellulose interactions in paper filter for advanced separation applications such as virus removal filtration and bioprocessing. The protein recovery was measured for bovine serum albumin (BSA), gamma-globulin, and lysozyme using biuret total protein reagent and polyacrylamide gel electrophoresis (PAGE), and the throughput was characterized in terms of flux values from fixed volume filtrations at various protein concentrations and under worst case experimental conditions. The affinity of cellulose to bind various proteins, such as BSA, lysozyme, gamma-globulin, and human IgG was quantified using a quartz crystal microbalance (QCMB) by developing a new method of fixing the cellulose fibers to the electrode surface without cellulose dissolution-precipitation. It was shown that the. mille-feuille filter exhibits high protein recovery, that is, similar to 99% for both BSA and lysozyme. However, gamma-globulin does not pass through the membrane due to its large size (i.e., >180 kDa). The PAGE data show no substantial change in the amount of dimers and trimers before and after filtration. QCMB analysis suggests a low affinity between the nanocellulose surface and proteins. The nanocellulose-based filter exhibits desirable inertness as a filtering material intended for protein purification.

  • 8. Gustafsson, Simon
    et al.
    Mihranyan, Albert
    Comparison of Nitrogen Gas Sorption, DSC Cryoporometry and Liquid-liquid Porometry for Probing of the Pore Size Distribution of Virus Filter Paper2018Conference paper (Refereed)
  • 9.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Investigating Protein Throughput, Vmax Values and Virus Removal Efficiency of the Paper Based Mille-Feuille Filter2017In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 253Article in journal (Other academic)
    Abstract [en]

    In this work we present Vmax values and throughput for the nanocellulose-based Mille-feuille virus removal filter paper as well as evaluate the affinity of different proteins for the cellulose surface using quartz crystal microbalance (QCMB). The Minute Virus of Mice (MVM) virus removal result for the Mille-feuille filter is also presented. The nanocellulose-based Mille-feuille filter is a non-woven, µm-thick filter paper with a narrow and tailorable pore size distribution, highly suitable for removing viruses of all sizes, including the worst case model Minute Virus of Mice (MVM). It is produced by hot-pressing method rather than by phase-inversion which is otherwise used to manufacture industrial analogues. Robust and cost-efficient virus removal processes are in high demand for the biotechnology industry, especially for the production of monoclonal antibodies derived from mammalian cell lines, therapeutic proteins derived from human plasma, and cell culture media. Non-woven filters have the advantage in contrast to regular phase-inversion made filters of a much higher porosity. For instance, the Mille-feuille filter has a porosity of 42% compared to 10-15% of the functional skin layer in asymmetric virus removal filters used today. In theory a higher porosity will result in higher flow rates. However, it also means that there is a larger filter area exposed to filtrate. Therefore investigating the surface affinity for proteins with different hydrophobicity and charge using QCMB is of great importance to be able to predict protein filtration behaviour. The presented work is a part of continuous efforts to develop a new class of highly efficient and affordable virus removal filters.

  • 10.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    On tailoring and validating the pore size distribution of nanocellulose based virus removal filter2016Conference paper (Refereed)
    Abstract [en]

    This work explores the possibility of controlling the pore size distribution of the nanocellulose based virus removal membrane by altering its manufacturing conditions. Further, the capacity of the nanocellulose filter toward surrogate 20 and 50 nm Au NPs is validated quantitatively. The nanocellulose-based membrane is a non-woven, µm-thick filter paper with a narrow and tailorable pore size distribution, highly suitable for virus removal as previously shown for large 80-100 nm viruses, e.g. swine influenza virus (SIV) and xenotropic murine leukemia virus (xMULV).

    [1, 2]

    It is produced by hot-pressing method rather than by phase-inversion which is otherwise used to manufacture industrial analogues. Robust and cost-efficient virus removal processes are in high demand for the biotechnology industry, especially for the production of monoclonal antibodies derived from mammalian cell lines, therapeutic proteins derived from human plasma, and cell culture media. By physically removing virus particles with size exclusion filters, viruses can be selectively separated from proteins, and thus the risk of infection can be mitigated. The presented work is part of continuous efforts to develop a new type of paper filter that can also remove the smallest and most resistant to inactivation viruses, such as parvovirus, featuring a typical particle size around 20 nm. The work summarizes the results from a number of characterisations including e.g. SEM images of the membrane pre- and post filtration of surrogate gold Au NPs as well as BJH gas desorption analysis of data for pore size distribution.

  • 11.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strategies for Tailoring the Pore-Size Distribution of Virus Retention Filter Papers2016In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 8, no 22, p. 13759-13767Article in journal (Refereed)
    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.

  • 12.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    The Mille-feuille filter paper2016Conference paper (Refereed)
  • 13.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    The Mille-feuille Virus Filter2015In: Uppsala Biomaterials Conference  2015, Uppsala, 2015Conference paper (Refereed)
  • 14.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Roemer, Laura
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Comparison of DSC cryoporomtery and liquid-liquid porometry for validation of pore size distributions of nanocellulose-based virus removal filter papers2018In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Article in journal (Refereed)
  • 15. Gustafsson, Simon
    et al.
    Westermann, Frank
    Hanrieder, Tobias
    Jung, Laura
    Ruppach, Horst
    Mihranyan, Albert
    Characterization of Regular and Cross-linked Virus Removal Filter Papers: Comparative Analysis of Dry and Wet Porometry Methods and Virus Removal PropertiesManuscript (preprint) (Other academic)
  • 16.
    Gustafsson, Simon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Westermann, Frank
    Charles River Biopharmaceut Serv, Gottfried Hagen Str 20, D-51105 Cologne, Germany.
    Hanrieder, Tobias
    Charles River Biopharmaceut Serv, Gottfried Hagen Str 20, D-51105 Cologne, Germany.
    Jung, Laura
    Charles River Biopharmaceut Serv, Gottfried Hagen Str 20, D-51105 Cologne, Germany.
    Ruppach, Horst
    Charles River Biopharmaceut Serv, Gottfried Hagen Str 20, D-51105 Cologne, Germany.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Comparative Analysis of Dry and Wet Porometry Methods for Characterization of Regular and Cross-Linked Virus Removal Filter Papers2019In: Membranes, ISSN 2077-0375, E-ISSN 2077-0375, Vol. 9, no 1, article id 1Article in journal (Refereed)
    Abstract [en]

    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.

  • 17.
    Hua, Kai
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Rocha, Igor
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Minist Educ Brazil, CAPES Fdn, BR-70040020 Brasilia, DF, Brazil.
    Zhang, Peng
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ning, Yi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Transition from bioinert to bioactive material by tailoring the biological cell response to carboxylated nanocellulose2016In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, no 3, p. 1224-1233Article in journal (Refereed)
    Abstract [en]

    This work presents an insight into the relationship between cell response and physicochemical properties of Cladophora cellulose (CC) by investigating the effect of CC functional group density on the response of model cell lines. CC was carboxylated by electrochemical TEMPO-mediated oxidation. By varying the amount of charge passed through the electrolysis setup, CC materials with different degrees of oxidation were obtained. The effect of carboxyl group density on the material’s physicochemical properties was investigated together with the response of human dermal fibroblasts (hDF) and human osteoblastic cells (Saos-2) to the carboxylated CC films. The introduction of carboxyl groups resulted in CC films with decreased specific surface area and smaller total pore volume compared with the unmodified CC (u-CC). While u-CC films presented a porous network of randomly oriented fibers, a compact and aligned fiber pattern was depicted for the carboxylated-CC films. The decrease in surface area and total pore volume, and the orientation and aggregation of the fibers tended to augment parallel to the increase in the carboxyl group density. hDF and Saos-2 cells presented poor cell adhesion and spreading on u-CC, which gradually increased for the carboxylated CC as the degree of oxidation increased. It was found that a threshold value in carboxyl group density needs be reached to obtain a carboxylated-CC film with cytocompatibility comparable to commercial tissue culture material. Hence, this study demonstrates that a normally bioinert nanomaterial can be rendered bioactive by carefully tuning the density of charged groups on the material surface, a finding that not only may contribute to the fundamental understanding of biointerface phenomena, but also to the development of bioinert/bioactive materials.

  • 18. Manukyan, Levon
    et al.
    Pengfei, Li
    Gustafsson, Simon
    Mihranyan, Albert
    Growth Media Filtration Using Nanocellulose-based Virus Removal Filter for Upstream Biopharmaceutical Processing2018In: Journal of Membrane Science, ISSN 0376-7388, E-ISSN 1873-3123Article in journal (Other academic)
  • 19.
    Manukyan, Levon
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Pengfei, Li
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Growth Media Filtration Using Nanocellulose-based Virus Removal Filter for Upstream Biopharmaceutical Processing2019In: Journal of Membrane Science, ISSN 0376-7388, E-ISSN 1873-3123, Vol. 572, p. 464-474Article in journal (Refereed)
    Abstract [en]

    The feasibility of using nanocellulose-based mille-feuille filter paper for upstream applications in serum-free growth media filtration, i.e. Dulbecco’s modified Eagle’s medium (DMEM) and Luria-Bertani medium (LBM), was tested. The filter performance with respect to F.174 bacteriophage (28nm) removal as a model small-size virus was characterized for filters of varying thicknesses, i.e. 11 and 33 mu m, at varying operating pressures, i.e. 1 and 3bar. The filters demonstrated generally good model small-size virus removal properties with LRV = 5, especially for 33 mu m filters. The 33 mu m filters were more robust and exhibited better virus removal and throughput properties than 11 mu m filters, although their flux was generally lower. The performance of the 33 and 11 mu m nanocellulose-based filter papers was further verified for upscaled bioporcessing by 10-fold increase in the loading volume. The results of the present work show that the 33 mu m nanocellulose-based filter paper could be an interesting alternative for large volume cell culture medium filtration during upstream bioprocessing.

  • 20. Pochard, Isabelle
    et al.
    Frykstrand, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Eriksson, Joakim
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Dielectric Spectroscopy Study of Water Behavior in Calcined Upsalite: A Mesoporous Magnesium Carbonate without Organic Surface Groups2015In: The Journal of Physical Chemistry C, ISSN 1932-7447, E-ISSN 1932-7455, Vol. 119, no 27, p. 15680-15688Article in journal (Refereed)
    Abstract [en]

    The water sorption properties and the dielectric spectroscopy response of calcined Upsalite?, a novel mesoporous and amorphous magnesium carbonate material candidate for several life-science based application areas, were investigated. The calcination of Upsalite? at 250°C, which removes organic groups present in the uncalcined material, is found to significantly affect the behaviour of adsorbed water. The proportion of free to bound water is considerably higher in the calcined material as compared to the uncalcined counterpart for relative humidities above ? 80 %. The amount of free water in calcined Upsalite? remains high even when the relative humidity is subsequently decreased and is the most likely cause of crystallization of the material into nesquehonite upon high humidity storage. In chorus, the presence of organic groups in uncalcined Upalite? most likely accounts for the higher binding degree of adsorbed water and, thus, the less likelihood of water-induced crystallization of this version of the material. Two dielectric relaxation processes were observed in calcined Upsalite? and were attributed to a Maxwell-Wagner and a Stern-layer relaxation process, respectively. The presented results create a fundamental understanding of water interaction properties in the novel mesoporous magnesium carbonate material Upsalite? and are expected to facilitate optimization of the stability of the material while simultaneously ensuring the lack of toxic surface groups; properties of importance for novel drug formulations and other life-science applications.

  • 21.
    Ruan, Changqing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Lindh, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Cellulose nanofibers prepared via pretreatment based on Oxone® oxidation2017In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, no 12, article id 2177Article in journal (Refereed)
    Abstract [sv]

    Softwood sulfite bleached cellulose pulp was oxidized with Oxone (R) and cellulose nanofibers (CNF) were produced after mechanical treatment with a high-shear homogenizer. UV-vis transmittance of dispersions of oxidized cellulose with different degrees of mechanical treatment was recorded. Scanning electron microscopy (SEM) micrographs and atomic force microscopy (AFM) images of samples prepared from the translucent dispersions showed individualized cellulose nanofibers with a width of about 10 nm and lengths of a few hundred nm. All results demonstrated that more translucent CNF dispersions could be obtained after the pretreatment of cellulose pulp by Oxone (R) oxidation compared with the samples produced without pretreatment. The intrinsic viscosity of the cellulose decreased after oxidation and was further reduced after mechanical treatment. Almost translucent cellulose films were prepared from the dispersions of individualized cellulose nanofibers. The procedure described herein constitutes a green, novel, and efficient route to access CNF.

  • 22.
    Tummala, Gopi Krishna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Felde, Nadja
    Fraunhofer Institute for Applied Optics and Precision Engineering.
    Gustafsson, Simon
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bubholz, Adrian
    Fraunhofer Institute for Applied Optics and Precision Engineering.
    Schröder, Sven
    Fraunhofer Institute for Applied Optics and Precision Engineering.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Light scattering in poly (vinyl alcohol) hydrogels reinforced with nanocellulose for ophthalmic use2017In: Optical Materials Express, ISSN 2159-3930, E-ISSN 2159-3930, Vol. 7, no 8, p. 2824-2837Article in journal (Refereed)
    Abstract [en]

    Scattering of ophthalmic devices is a complex phenomenon involving both surface and bulk light-material interactions. In this work, light scattering of nanocellulose reinforced PVA hydrogels contact lenses for ophthalmic applications was investigated. Optical microscopy, fluorescence microscopy and atomic force microscopy (AFM) techniques were used for ultrastructure characterization. Further, 3D angle resolved light scattering measurements in the visible spectral range were performed using a BTDF (bidirectional transmittance distribution function) sensor to quantify the scattered light. Surface and bulk scattering properties were discerned using white light interferometry. Total scatter levels ranging from 3% to 40% were observed depending on the hydrogel composition. The most critical factor affecting the light scattering properties in nanocellulose-reinforced PVA hydrogels was related to the state of hydration of the hydrogels, which is critical to maintain visual acuity of ophthalmic devices.

1 - 22 of 22
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