Physical cell separation using microfluidic funnel ratchets

The separation of biological cells using non-chemical methods is important to many areas of medicine and biology. Filtration through microstructured constrictions is one such method where cells can be separated by a combination of size and deformability. This technique, however, is limited by unpredictable variations of the filter hydrodynamic resistance as cells accumulate in the microstructure. Applying a reverse flow to unclog the filter will undo the separation and reduce filter selectivity because of the reversibility of low-Reynolds number flow. This work introduces a microfluidic structural ratchet mechanism to separate cells using oscillatory flow through a 2-dimensional array of funnel-shaped structures. Devices are fabricated using multi-layer soft lithography of polydimethylsiloxane (PDMS) and flow is controlled using pressure sources and on-chip membrane valves. An iterative procedure of design and testing is used to produce a final device which is characterized by the sorting and separation of L1210 mouse lymphoma cells (MLCs), peripheral blood mononuclear cells (PBMCs) from healthy donors, as well as polystyrene microparticles. The ability of this mechanism to sort and separate cells/particles based on size and deformability is investigated and confirmed. Additionally, the spatial distribution of cells after sorting is demonstrated to
be repeatable and the separation process is shown to be irreversible. This mechanism can be applied generally to separate cells that differ by size and/or deformability.

McFaul, S.M.

University of British Columbia




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