Deformability-induced lift force in spiral microchannels for cell separation

Ewa Guzniczak*, Oliver Otto, Graeme Whyte, Nicholas Willoughby, Melanie Jimenez, Helen Bridle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Cell sorting and isolation from a heterogeneous mixture is a crucial task in many aspects of cell biology, biotechnology and medicine. Recently, there has been an interest in methods allowing cell separation upon their intrinsic properties such as cell size and deformability, without the need for use of biochemical labels. Inertial focusing in spiral microchannels has been recognised as an attractive approach for high-throughput cell sorting for myriad point of care and clinical diagnostics. Particles of different sizes interact to a different degree with the fluid flow pattern generated within the spiral microchannel and that leads to particles ordering and separation based on size. However, the deformable nature of cells adds complexity to their ordering within the spiral channels. Herein, an additional force, deformability-induced lift force (FD), involved in the cell focusing mechanism within spiral microchannels has been identified, investigated and reported for the first time, using a cellular deformability model (where the deformability of cells is gradually altered using chemical treatments). Using this model, we demonstrated that spiral microchannels are capable of separating cells of the same size but different deformability properties, extending the capability of the previous method. We have developed a unique label-free approach for deformability-based purification through coupling the effect of FD with inertial focusing in spiral microchannels. This microfluidic-based purification strategy, free of the modifying immuno-labels, allowing cell processing at a large scale (millions of cells per min and mls of medium per minute), up to high purities and separation efficiency and without compromising cell quality.

Original languageEnglish
Pages (from-to)614-625
Number of pages12
JournalLab on a Chip
Volume20
Issue number3
DOIs
Publication statusPublished - 7 Feb 2020

Funding

FACS sorting was performed in the University of Edinburgh FACS Facility by Dr Martin Waterfall. Jurkat cells expressing green fluorescence protein (GFP+), were kindly provided by Dr Miguel Hermida (Heriot-Watt University, UK). EG gratefully acknowledges the funding from Scottish Industrial Biotechnology Innovation Centre (IBioIC) for her doctoral studies, Royal Society of Edinburgh for the JM Lessells travel scholarship allowing visiting OO's lab and performing the experimental work as well as Epigem Ltd. for providing resources for this project. OO gratefully acknowledges funding from the German Federal Ministry of Education and Research (ZIK grant under grant agreement 03Z22CN11) and from the Deutschen Zentrum f\u00FCr Herz-Kreislaufforschung. MJ was supported by the Royal Academy of Engineering under the Research Fellowship scheme (RF/ 201718/1741). MJ would also like to thank the Engineering and Physical Sciences Research Council (EPSRC) for their support (EP/R006482/1). The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers. FACS sorting was performed in the University of Edinburgh FACS Facility by Dr Martin Waterfall. Jurkat cells expressing green fluorescence protein (GFP+), were kindly provided by Dr Miguel Hermida (Heriot-Watt University, UK). EG gratefully acknowledges the funding from Scottish Industrial Biotechnology Innovation Centre (IBioIC) for her doctoral studies, Royal Society of Edinburgh for the JM Lessells travel scholarship allowing visiting OO's lab and performing the experimental work as well as Epigem Ltd. for providing resources for this project. OO gratefully acknowledges funding from the German Federal Ministry of Education and Research (ZIK grant under grant agreement 03Z22CN11) and from the Deutschen Zentrum f\u00FCr Herz-Kreislaufforschung. Notes and references. MJ would like to thank the Engineering and Physical Sciences Research Council (EPSRC) and the Royal Academy of Engineering for her Personal Research Fellowship (EP/R006482/1 and RF/201718/1741).

Keywords

  • cell sorting
  • cell biology
  • cell separation

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