A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration

Emerging as a promising pathway to HIV vaccines, Virus-Like Particles (VLPs) have drawn considerable attention in recent years. A challenge of working with HIV VLPs in biopharmaceutical processes is their low rigidity, and factors such as shear stress, osmotic pressure and pH variation have to be re...

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Main Authors: Tobias Wolf, Jamila Rosengarten, Ina Härtel, Jörn Stitz, Stéphan Barbe
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Membranes
Subjects:
Online Access:https://www.mdpi.com/2077-0375/12/12/1248
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author Tobias Wolf
Jamila Rosengarten
Ina Härtel
Jörn Stitz
Stéphan Barbe
author_facet Tobias Wolf
Jamila Rosengarten
Ina Härtel
Jörn Stitz
Stéphan Barbe
author_sort Tobias Wolf
collection DOAJ
description Emerging as a promising pathway to HIV vaccines, Virus-Like Particles (VLPs) have drawn considerable attention in recent years. A challenge of working with HIV VLPs in biopharmaceutical processes is their low rigidity, and factors such as shear stress, osmotic pressure and pH variation have to be reduced during their production. In this context, the purification and concentration of VLPs are often achieved by means of Tangential Flow Filtration (TFF) involving ultrafiltration hollow fiber modules. Despite the urgent need for robust upscaling strategies and further process cost reduction, very little attention has been dedicated to the identification of the mechanisms limiting the performance of HIV VLP TFF processes. In this work, for the first time, a hydrodynamic approach based on particle friction was successfully developed as a methodology for both the optimization and the upscaling of HIV VLP TFF. Friction forces acting on near-membrane HIV VLPs are estimated, and the plausibility of the derived static coefficients of friction is discussed. The particle friction-based model seems to be very suitable for the fitting of experimental data related to HIV VLP TFF as well as for upscaling projections. According to our predictions, there is still considerable room for improvement of HIV VLP TFF, and operating this process at slightly higher flow velocities may dramatically enhance the efficiency of VLP purification and concentration. This work offers substantial guidance to membrane scientists during the design of upscaling strategies for HIV VLP TFF.
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spelling doaj.art-b182b6e276dd425e8a9329a490fb7a012023-11-24T16:36:00ZengMDPI AGMembranes2077-03752022-12-011212124810.3390/membranes12121248A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow FiltrationTobias Wolf0Jamila Rosengarten1Ina Härtel2Jörn Stitz3Stéphan Barbe4Research Group Process Engineering, Faculty of Applied Natural Sciences, TH Köln—University of Applied Sciences, Campusplatz 1, 51379 Leverkusen, GermanyInstitute of Technical Chemistry, Leibniz University Hannover, Callinstraße 5, 30167 Hannover, GermanyResearch Group Process Engineering, Faculty of Applied Natural Sciences, TH Köln—University of Applied Sciences, Campusplatz 1, 51379 Leverkusen, GermanyResearch Group Pharmaceutical Biotechnology, Faculty of Applied Natural Sciences, TH Köln—University of Applied Sciences, Campusplatz 1, 51379 Leverkusen, GermanyResearch Group Process Engineering, Faculty of Applied Natural Sciences, TH Köln—University of Applied Sciences, Campusplatz 1, 51379 Leverkusen, GermanyEmerging as a promising pathway to HIV vaccines, Virus-Like Particles (VLPs) have drawn considerable attention in recent years. A challenge of working with HIV VLPs in biopharmaceutical processes is their low rigidity, and factors such as shear stress, osmotic pressure and pH variation have to be reduced during their production. In this context, the purification and concentration of VLPs are often achieved by means of Tangential Flow Filtration (TFF) involving ultrafiltration hollow fiber modules. Despite the urgent need for robust upscaling strategies and further process cost reduction, very little attention has been dedicated to the identification of the mechanisms limiting the performance of HIV VLP TFF processes. In this work, for the first time, a hydrodynamic approach based on particle friction was successfully developed as a methodology for both the optimization and the upscaling of HIV VLP TFF. Friction forces acting on near-membrane HIV VLPs are estimated, and the plausibility of the derived static coefficients of friction is discussed. The particle friction-based model seems to be very suitable for the fitting of experimental data related to HIV VLP TFF as well as for upscaling projections. According to our predictions, there is still considerable room for improvement of HIV VLP TFF, and operating this process at slightly higher flow velocities may dramatically enhance the efficiency of VLP purification and concentration. This work offers substantial guidance to membrane scientists during the design of upscaling strategies for HIV VLP TFF.https://www.mdpi.com/2077-0375/12/12/1248virus-like particletangential flow filtrationparticle polarization layerdownstream process
spellingShingle Tobias Wolf
Jamila Rosengarten
Ina Härtel
Jörn Stitz
Stéphan Barbe
A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
Membranes
virus-like particle
tangential flow filtration
particle polarization layer
downstream process
title A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
title_full A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
title_fullStr A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
title_full_unstemmed A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
title_short A Hydrodynamic Approach to the Study of HIV Virus-Like Particle (VLP) Tangential Flow Filtration
title_sort hydrodynamic approach to the study of hiv virus like particle vlp tangential flow filtration
topic virus-like particle
tangential flow filtration
particle polarization layer
downstream process
url https://www.mdpi.com/2077-0375/12/12/1248
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