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Publications (10 of 144) Show all publications
Gustafsson, S. & Mihranyan, A. (2017). Investigating Protein Throughput, Vmax Values and Virus Removal Efficiency of the Paper Based Mille-Feuille Filter. In: : . Paper presented at ACS National Meeting - San Francisco 2017 253rd American Chemical Society National Meeting & Expo. .
Open this publication in new window or tab >>Investigating Protein Throughput, Vmax Values and Virus Removal Efficiency of the Paper Based Mille-Feuille Filter
2017 (English)Conference paper, Poster (with or without abstract) (Refereed)
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.

National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-332593 (URN)
Conference
ACS National Meeting - San Francisco 2017 253rd American Chemical Society National Meeting & Expo
Funder
Knut and Alice Wallenberg Foundation
Available from: 2017-10-30 Created: 2017-10-30 Last updated: 2017-12-08Bibliographically approved
Gustafsson, S., Manukyan, L. & Mihranyan, A. (2017). Protein-Nanocellulose Interactions in Paper Filters for Advanced Separation Applications. Langmuir, 33(19), 4729-4736.
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: 2017-11-23
Tummala, G. K., Joffre, T., Rojas, R., Persson, C. & Mihranyan, A. (2017). Strain-induced stiffening of nanocellulose-reinforced poly(vinyl alcohol) hydrogels mimicking collagenous soft tissues. Soft Matter, 13(21), 3936-3945.
Open this publication in new window or tab >>Strain-induced stiffening of nanocellulose-reinforced poly(vinyl alcohol) hydrogels mimicking collagenous soft tissues
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2017 (English)In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 13, no 21, p. 3936-3945Article in journal (Refereed) Published
Abstract [en]

Soft tissues possess remarkable mechanical strength for their high water content, which is hard to mimic in synthetic materials. Here, we demonstrate how strain-induced stiffening in hydrogels plays a major role in mimicking the mechanical properties of collagenous soft tissues. In particular, nanocellulose reinforced polyvinyl alcohol (PVA) hydrogels of exceptionally high water content (90-93 wt%) are shown to exhibit collagen-like mechanical behavior typical for soft tissues. High water content and co-existence of both soft and rigid domains in the gel network are the main factors responsible for strain-induced stiffening. This observed effect due to the alignment of rigid components of the hydrogel is simulated through modeling and visualized through strain-induced birefringence experiments. Design parameters such as nanocellulose aspect ratio and solvent composition are also shown to be important to control the mechanical properties. In addition, owing to their transparency (90-95% at 550 nm) and hyperelastic properties (250-350% strain), the described hydrogels are promising materials for biomedical applications, especially in ophthalmology.

National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-326502 (URN)10.1039/c7sm00677b (DOI)000402744100012 ()28504291 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council Formas, 232-2014-202
Available from: 2017-07-13 Created: 2017-07-13 Last updated: 2017-11-23
Rocha, I., Ferraz, N., Mihranyan, A., Strömme, M. & Lindh, J. (2016). Chemical modifications of Cladophorananocellulose to provide a non-toxicmaterial with anticoagulant properties. In: : . Paper presented at 10th World Biomaterials Congress. Montreal, Canada.
Open this publication in new window or tab >>Chemical modifications of Cladophorananocellulose to provide a non-toxicmaterial with anticoagulant properties
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2016 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
Montreal, Canada: , 2016
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-296229 (URN)
Conference
10th World Biomaterials Congress
Available from: 2016-06-14 Created: 2016-06-14 Last updated: 2016-11-30
Xu, C., Carlsson, D. O. & Mihranyan, A. (2016). Feasibility of using DNA-immobilized nanocellulose-based immunoadsorbent for systemic lupus erythematosus plasmapheresis. Colloids and Surfaces B: Biointerfaces, 143, 1-6.
Open this publication in new window or tab >>Feasibility of using DNA-immobilized nanocellulose-based immunoadsorbent for systemic lupus erythematosus plasmapheresis
2016 (English)In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 143, p. 1-6Article in journal (Refereed) Published
Abstract [en]

The goal of this project was to study the feasibility of using a DNA-immobilized nanocellulose-based immunoadsorbent for possible application in medical apheresis such as systemic lupus erythematosus (SLE) treatment. Calf thymus DNA was bound to high surface area nanocellulose membrane at varying concentrations using UV-irradiation. The DNA-immobilized samples were characterized with scanning electron microscopy, atomic force microscopy, and phosphorus elemental analysis. The anti-ds-DNA IgG binding was tested in vitro using ELISA. The produced sample showed high affinity in vitro to bind anti-ds-DNA-antibodies from mice, as much as 80% of added IgG was bound by the membrane. Furthermore, the binding efficiency was quantitatively dependent on the amount of immobilized DNA onto nanocellulose membrane. The described nanocellulose membranes are interesting immunoadsorbents for continued clinical studies.

Keyword
Autoimmune diseases; DNA immobilization; Immunoadsorption; Nanocellulose; Systemic lupus erythematosus
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-287474 (URN)10.1016/j.colsurfb.2016.03.014 (DOI)000376696900001 ()27011345 (PubMedID)
External cooperation:
Funder
Knut and Alice Wallenberg FoundationGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology
Available from: 2016-04-25 Created: 2016-04-25 Last updated: 2017-11-30Bibliographically approved
Tummala, G. K., Joffre, T., Lopes, V., Liszka, A., Buznyk, O., Ferraz, N., . . . Mihranyan, A. (2016). Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications. ACS Biomaterials Science and Engineering, 2(11), 2072-2079.
Open this publication in new window or tab >>Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications
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2016 (English)In: ACS Biomaterials Science and Engineering, ISSN 2373-9878, Vol. 2, no 11, p. 2072-2079Article in journal (Refereed) Published
Abstract [en]

A nanocellulose-reinforced poly(vinyl alcohol) hydrogel material of exceptionally high water content for ophthalmic applications is presented (>90 wt %), which also features a hitherto unprecedented combination of optical, mechanical, viscoelastic, oxygen permeability, and biocompatibility properties. The hydrogel combines the desired softness with remarkable strain-dependent mechanical strength and thereby demonstrates hyperelastic, rubber-like mechanical properties. The observed unusual mechanical behavior is due to both high water content and the combination of relatively stiff cellulose nanowhiskers entangled in a soft polymer matrix of poly(vinyl alcohol) (PVA), thus mimicking the structural characteristics of the cornea's main constituents, i.e., water and collagen.

Keyword
biocompatibility, cellulose nanocrystals, contact lens, ophthalmic prosthesis, poly(vinyl alcohol)
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-310474 (URN)10.1021/acsbiomaterials.6b00484 (DOI)000388161200027 ()2-s2.0-84995379882 (Scopus ID)
Projects
WWSC
Funder
Knut and Alice Wallenberg FoundationVINNOVA, 2013-04645
Available from: 2016-12-16 Created: 2016-12-16 Last updated: 2017-02-06Bibliographically approved
Gustafsson, S., Lordat, P., Hanrieder, T., Asper, M., Schaefer, O. & Mihranyan, A. (2016). Mille-feuille paper: a novel type of filter architecture for advanced virus separation applications. Materials Horizons, 3(4), 320-327.
Open this publication in new window or tab >>Mille-feuille paper: a novel type of filter architecture for advanced virus separation applications
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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: 2017-11-30Bibliographically approved
Mihranyan, A. (2016). Nanocellulose reinforced contact lens for ophthalmic use: PAPER ID: 2385082; final paper number: CELL 360. In: : . Paper presented at ACS 251st National Meeting, San Diego. .
Open this publication in new window or tab >>Nanocellulose reinforced contact lens for ophthalmic use: PAPER ID: 2385082; final paper number: CELL 360
2016 (English)Conference paper, Oral presentation only (Refereed)
National Category
Nano Technology
Identifiers
urn:nbn:se:uu:diva-287465 (URN)
Conference
ACS 251st National Meeting, San Diego
Funder
Knut and Alice Wallenberg Foundation
Available from: 2016-04-25 Created: 2016-04-25 Last updated: 2016-04-25
Gustafsson, S. & Mihranyan, A. (2016). On tailoring and validating the pore size distribution of nanocellulose based virus removal filter. In: : . Paper presented at American Chemical Society 2016 San Diego. .
Open this publication in new window or tab >>On tailoring and validating the pore size distribution of nanocellulose based virus removal filter
2016 (English)Conference paper, Poster (with or without abstract) (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.

National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-284414 (URN)
Conference
American Chemical Society 2016 San Diego
Funder
Knut and Alice Wallenberg Foundation
Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2016-11-25Bibliographically approved
Tummala, G. K., Rojas, R. & Mihranyan, A. (2016). Poly(vinyl alcohol) Hydrogels Reinforced with Nanocellulose for Ophthalmic Applications: General Characteristics and Optical Properties. Journal of Physical Chemistry B, 120(51), 13094-13101.
Open this publication in new window or tab >>Poly(vinyl alcohol) Hydrogels Reinforced with Nanocellulose for Ophthalmic Applications: General Characteristics and Optical Properties
2016 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 120, no 51, p. 13094-13101Article in journal (Refereed) Published
Abstract [en]

Globally, uncorrected refractive errors are one of the main causes of visual impairment, and contact lenses form an important part of modern day eye care and culture. Several hydrogels with varying physicochemical properties are in use to manufacture soft contact lenses. Hydrogels are generally too soft and reinforcement with appropriate materials is desirable to achieve high water content without compromising mechanical properties. In this study, we have developed a highly transparent macroporous hydrogel with water content >90%, by combining poly(vinyl alcohol) with nanocellulose. Furthermore, the results show that the composite hydrogel has refractive index close to that of water and very good UV-blocking properties.

Keyword
nanocellulose, polyvinyl alcohol, transparent, optical properties, contact lens
National Category
Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-310405 (URN)10.1021/acs.jpcb.6b10650 (DOI)000391160300010 ()
Projects
WWSC
Funder
Knut and Alice Wallenberg Foundation
Available from: 2016-12-15 Created: 2016-12-15 Last updated: 2017-11-23
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8105-2317

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