Human leucocytes processed by fast-rate inertial microfluidics retain conventional functional characteristics

Thomas Carvell, Paul Burgoyne, Laura Milne, John D. M. Campbell, Alasdair R. Fraser, Helen Bridle

Research output: Contribution to journalArticlepeer-review

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Abstract

The manufacturing of clinical cellular therapies is a complex process frequently requiring manipulation of cells, exchange of buffers and volume reduction. Current manufacturing processes rely on either low throughput open centrifugation-based devices, or expensive closed-process alternatives. Inertial focusing (IF) microfluidic devices offer the potential for high-throughput, inexpensive equipment which can be integrated into a closed system, but to date no IF devices have been approved for use in cell therapy manufacturing, and there is limited evidence for the effects that IF processing has on human cells. The IF device described in this study was designed to simultaneously separate leucocytes, perform buffer exchange and provide a volume reduction to the cell suspension, using high flow rates with high Reynolds numbers. The performance and effects of the IF device were characterized using peripheral blood mononuclear cells and isolated monocytes. Post-processing cell effects were investigated using multi-parameter flow cytometry to track cell viability, functional changes and fate. The IF device was highly efficient at separating CD14+ monocytes (approx. 97% to one outlet, approx. 60% buffer exchange, 15 ml min−1) and leucocyte processing was well tolerated with no significant differences in downstream viability, immunophenotype or metabolic activity when compared with leucocytes processed with conventional processing techniques. This detailed approach provides robust evidence that IF devices could offer significant benefits to clinical cell therapy manufacture.
Original languageEnglish
Article number20230572
JournalJournal of the Royal Society. Interface
Volume21
Issue number212
Early online date6 Mar 2024
DOIs
Publication statusPublished - Mar 2024

Keywords

  • advanced therapy medicinal products
  • cell therapy
  • inertial focusing
  • medium exchange
  • microfluidics
  • viability

ASJC Scopus subject areas

  • Bioengineering
  • Biophysics
  • Biochemistry
  • Biotechnology
  • Biomedical Engineering
  • Biomaterials

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