Role of Microfiltration Membrane Morphology on Nanoparticle Purification to Enhance Downstream Purification of Viral Vectors

Mara Leach, Catherine Cox, Sumith Ranil Wickramasinghe, Malgorzata Chwatko, Dibakar Bhattacharyya

Research output: Contribution to journalArticlepeer-review

Abstract

In the rapidly advancing realms of gene therapy and biotechnology, the efficient purification of viral vectors is pivotal for ensuring the safety and efficacy of gene therapies. This study focuses on optimizing membrane selection for viral vector purification by evaluating key properties, including porosity, thickness, pore structure, and hydrophilicity. Notably, we employed adeno-associated virus (AAV)-sized nanoparticles (20 nm), 200 nm particles, and bovine serum albumin (BSA) to model viral vector harvesting. Experimental data from constant pressure normal flow filtration (NFF) at 1 and 2 bar using four commercial flat sheet membranes revealed distinct fouling behaviors. Symmetric membranes predominantly showed internal and external pore blockage, while asymmetric membranes formed a cake layer on the surface. Hydrophilicity exhibited a positive correlation with recovery, demonstrating an enhanced recovery with increased hydrophilicity. Membranes with higher porosity and interpore connectivity showcased superior throughput, reduced operating time, and increased recovery. Asymmetric polyether sulfone (PES) membranes emerged as the optimal choice, achieving ∼100% recovery of AAV-sized particles, an ∼44% reduction in model cell debris (200 nm particles), an ∼35% decrease in BSA, and the fastest operating time of all membranes tested. This systematic investigation into fouling behaviors and membrane properties not only informs optimal conditions for viral vector recovery but also lays the groundwork for advancing membrane-based strategies in bioprocessing.

Original languageEnglish
Pages (from-to)3932-3941
Number of pages10
JournalACS Applied Bio Materials
Volume7
Issue number6
DOIs
StatePublished - Jun 17 2024

Bibliographical note

Publisher Copyright:
© 2024 American Chemical Society.

Keywords

  • bioseparations
  • gene therapy
  • microfiltration
  • nanoparticles
  • viral vectors

ASJC Scopus subject areas

  • Biomaterials
  • General Chemistry
  • Biomedical Engineering
  • Biochemistry, medical

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