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Membranes
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Application of Membrane Materials in Bioseparation and Downstream Processing
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Application of Membrane Materials in Bioseparation and Downstream Processing

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Membrane Applications for Other Areas".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 6842

Special Issue Editors

Dr. Wei Zhang

E-Mail Website
Guest Editor
Downstream Processing Group, Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), Singapore 138668, Singapore
Interests: purification process and analytics development for biologics, vaccines, cell and gene therapy, and nucleic acid therapy; continuous and intensified downstream processing; process scaling up and technical transfer to GMP facility
Prof. Dr. Lingxue Kong

E-Mail Website
Guest Editor
Institute for Frontier Materials, Deakin University, Waurn Ponds, VIC 3216, Australia
Interests: nanostructured membranes; porous materials; membrane characterization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In this Special Issue, authors are invited to submit original articles and reviews on the application of membrane materials in bioseparation and downstream processes. The contributions may concern (i) the development of new membrane materials with applications in bioseparation and downstream processes; (ii) the characterization of existing or new membrane materials with applications in bioseparation and downstream processes; (iii) the development of membrane materials for bioseparation and downstream processes; (iv) process optimization and scaling up to ulitize membrane materials for bioseparation and downstream processes; (v) the mechanisitic study of ulitizing membrane materials for bioseparation and downstream processes; (vi) the modelling of ulitizing membrane materials for bioseparation and downstream processes; (vii) the application of membrane materials to bioanalytics.

Dr. Wei Zhang
Prof. Dr. Lingxue Kong
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • membrane material
  • membrane chromatography
  • membrane filtration
  • bioseparation
  • downstream processing
  • charactarization
  • process development
  • process optimization
  • scale up
  • mechnisitic study
  • process modelling

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Further information on MDPI's Special Issue policies can be found here.

Published Papers (4 papers)

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Research

17 pages, 2695 KiB  
Article
Enhancing the Performance of Tangential Flow Microfiltration for Bioreactor Clarification
by Amir Hossein Mostafavi, Liang-Kai Chu, Xianghong Qian, John Paul Smelko, Da Zhang, Andrew Zydney and Sumith Ranil Wickramasinghe
Membranes 2025, 15(3), 78; https://doi.org/10.3390/membranes15030078 - 3 Mar 2025
Viewed by 266
Abstract
Tangential flow microfiltration is easily adapted for batch and continuous bioreactor clarification. The permeate can be introduced directly to the subsequent capture step. However, the commercial use of tangential flow filtration (TFF) is limited by membrane fouling, leading to a compromised performance. Here, [...] Read more.
Tangential flow microfiltration is easily adapted for batch and continuous bioreactor clarification. The permeate can be introduced directly to the subsequent capture step. However, the commercial use of tangential flow filtration (TFF) is limited by membrane fouling, leading to a compromised performance. Here, we explored the possibility of reducing membrane fouling by integrating a hydrocyclone as the primary clarification operation. The overflow from the hydrocyclone was introduced directly as the feed to the microfiltration module. Chinese hamster ovary cells were used as the feed stream to investigate the feasibility of this integrated process. A range of cell viabilities from 0% (cell lysate) to 96% were investigated. The cell densities ranged from 0.9 to 10 million cells per mL. Two commercially available hollow fiber microfiltration membranes were used, an essentially symmetric membrane and a reverse asymmetric membrane where the more open support structure faced the feed stream. The reverse asymmetric membrane was more resistant to fouling in the absence of an integrated hydrocyclone. Integrating a hydrocyclone led to a reduction in the flux decline for the symmetric membrane, but did not affect the performance of the reverse asymmetric membrane. The careful choice of membrane morphology and pore size is important when designing an integrated process. Full article
(This article belongs to the Special Issue Application of Membrane Materials in Bioseparation and Downstream Processing)
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14 pages, 1251 KiB  
Article
Enhancing Virus Filter Performance Through Pretreatment by Membrane Adsorbers
by Solomon Isu, Shu-Ting Chen, Raheleh Daneshpour, Hironobu Shirataki, Daniel Strauss, Andrew L. Zydney, Xianghong Qian and Sumith Ranil Wickramasinghe
Membranes 2025, 15(1), 34; https://doi.org/10.3390/membranes15010034 - 17 Jan 2025
Viewed by 1455
Abstract
Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody [...] Read more.
Virus filtration is used to ensure the high level of virus clearance required in the manufacture of biopharmaceutical products such as monoclonal antibodies. Flux decline during virus filtration can occur due to the formation of reversible aggregates consisting of self-assembled monomeric monoclonal antibody molecules, particularly at high antibody concentrations. While size exclusion chromatography is generally unable to detect these reversible aggregates, dynamic light scattering may be used to determine their presence. Flux decline during virus filtration may be minimized by pretreating the feed using a membrane adsorber in order to disrupt the reversible aggregates that are present. The formation of reversible aggregates is highly dependent on the monoclonal antibody and the feed conditions. For the pH values investigated here, pretreatment of the feed using a hydrophobic interaction membrane adsorber was the most effective in minimizing flux decline during virus filtration. Ion exchange membranes may also be effective if the monoclonal antibody and membrane are oppositely charged. Consequently, the effectiveness of ion exchange membrane adsorbers is much more dependent on solution pH when compared to hydrophobic interaction membrane adsorbers. Size based prefiltration was found to be ineffective at disrupting these reversible aggregates. These results can help guide the development of more effective virus filtration processes for monoclonal antibody production. Full article
(This article belongs to the Special Issue Application of Membrane Materials in Bioseparation and Downstream Processing)
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12 pages, 1758 KiB  
Communication
A Novel Method for Separating Full and Empty Adeno-Associated Viral Capsids Using Ultrafiltration
by Deepraj Sarmah and Scott M. Husson
Membranes 2024, 14(9), 194; https://doi.org/10.3390/membranes14090194 - 12 Sep 2024
Cited by 1 | Viewed by 2769
Abstract
Adeno-associated viral vectors (AAVs) are the predominant viral vectors used for gene therapy applications. A significant challenge in obtaining effective doses is removing non-therapeutic empty viral capsids lacking DNA cargo. Current methods for separating full (gene-containing) and empty capsids are challenging to scale, [...] Read more.
Adeno-associated viral vectors (AAVs) are the predominant viral vectors used for gene therapy applications. A significant challenge in obtaining effective doses is removing non-therapeutic empty viral capsids lacking DNA cargo. Current methods for separating full (gene-containing) and empty capsids are challenging to scale, produce low product yields, are slow, and are difficult to operationalize for continuous biomanufacturing. This communication demonstrates the feasibility of separating full and empty capsids by ultrafiltration. Separation performance was quantified by measuring the sieving coefficients for full and empty capsids using ELISA, qPCR, and an infectivity assay based on the live cell imaging of green fluorescent protein expression. We demonstrated that polycarbonate track-etched membranes with a pore size of 30 nm selectively permeated empty capsids to full capsids, with a high recovery yield (89%) for full capsids. The average sieving coefficients of full and empty capsids obtained through ELISA/qPCR were calculated as 0.25 and 0.49, indicating that empty capsids were about twice as permeable as full capsids. Establishing ultrafiltration as a viable unit operation for separating full and empty AAV capsids has implications for developing the scale-free continuous purification of AAVs. Full article
(This article belongs to the Special Issue Application of Membrane Materials in Bioseparation and Downstream Processing)
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14 pages, 2188 KiB  
Article
Comparative Analysis of the Impact of Protein on Virus Retention for Different Virus Removal Filters
by Mohammad A. Afzal, Joshua Peles and Andrew L. Zydney
Membranes 2024, 14(7), 158; https://doi.org/10.3390/membranes14070158 - 17 Jul 2024
Viewed by 1583
Abstract
The performance of virus filters is often determined by the extent of protein fouling, which can affect both filtrate flux and virus retention. However, the mechanisms governing changes in virus retention in the presence of proteins are still not well understood. The objective [...] Read more.
The performance of virus filters is often determined by the extent of protein fouling, which can affect both filtrate flux and virus retention. However, the mechanisms governing changes in virus retention in the presence of proteins are still not well understood. The objective of this work was to examine the effect of proteins on virus retention by both asymmetric (Viresolve® NFP and Viresolve® Pro) and relatively homogeneous (Ultipor® DV20 and PegasusTM SV4) virus filtration membranes. Experiments were performed with bacteriophage ϕX174 as a model parvovirus and human serum immunoglobulin G (hIgG) as a model protein. The virus retention in 1 g/L hIgG solutions was consistently less than that in a protein-free buffer solution by between 1 to 3 logs for the different virus filters. The virus retention profiles for the two homogeneous membranes were very similar, with the virus retention being highly correlated with the extent of flux decline. Membranes prefouled with hIgG and then challenged with phages also showed much lower virus retention, demonstrating the importance of membrane fouling; the one exception was the Viresolve® Pro membrane, which showed a similar virus retention for the prefouled and pristine membranes. Experiments in which the protein was filtered after the virus challenge demonstrated that hIgG can displace previously captured viruses from within a filter. The magnitude of these effects significantly varied for the different virus filters, likely due to differences in membrane morphology, pore size distribution, and chemistry, providing important insights into the development/application of virus filtration in bioprocessing. Full article
(This article belongs to the Special Issue Application of Membrane Materials in Bioseparation and Downstream Processing)
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