Summary: | Techniques for the separation of cells from heterogeneous samples that do not rely on
biological labels are important in applications where specific labels are unknown or
unavailable. However, limitations of existing label-free separation techniques have
prevented their widespread adoption. Those techniques that separate based on cell size
typically offer high throughput but lack specificity. Those that separate based on a
combination of cell size and deformability have superior selectivity, but are slow and prone
to clogging.
This work reports a microfluidic device that employs novel resettable cell traps to separate
cells based on size and deformability. The resettable cell trap is a microchannel with
controllable cross-section, featuring recesses to temporarily store captured cells. Larger and
less deformable cells flowing through a cell trap with constricted cross-section will be
selectively captured due to size restriction, and can be released back into the flow for
collection by enlarging the channel cross-section. Smaller and more deformable cells will
simply pass through the constricted channel. The ability to enlarge the trap and purge it of
captured cells enables long term operation without clogging. The cell separation device
presented is able to separate UM-UC13 cancer cells from human leukocytes with high
enrichment (~100x), retention (~90%) and throughput (450,000 cells/hour). Serial separation
using this mechanism provides extremely high enrichment (~2500x) without sacrificing
retention. The mechanism is also shown to resolve size differences of 1 µm between
polystyrene microspheres. The resettable cell trap is an improvement upon existing
technology, providing greater enrichment than possible through size-based techniques while
improving throughput and eliminating problems caused by clogging that are typical of
filtration based techniques.
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