Rare cell separation using resettable cell traps

• Main Author: Beattie, William
• Language: English
• Published: University of British Columbia 2013
• Online Access: http://hdl.handle.net/2429/44907

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.