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Highly selective biomechanical separation of cancer cells from leukocytes using microfluidic ratchets and hydrodynamic concentrator
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Image of FIG. 1.
FIG. 1.

Schematic of the cell separation chip. The cell mixture is first processed using the hydrodynamic concentrator to concentrate the sample and remove a portion of the contaminant leukocytes. The output accumulates in an intermediate reservoir. Next, the concentrated sample is separated using the ratchet cell sorter and the separated cancer cells are collected at the outlet.

Image of FIG. 2.
FIG. 2.

(a) Schematic of the concentrator mechanism. The fluid removal ports remove fluid containing some contaminant cells while target cells are retained and carried downstream along the bifurcated channel. (b) Target cancer cells enter the pinch constriction from different streamlines but are re-aligned at the constriction to streamlines adjacent to the inner side of the bifurcation channels. Length dimensions are shown in microns.

Image of FIG. 3.
FIG. 3.

Electric circuit analogy for a single concentrator mechanism. The outlet bifurcation channels are shown as a single combined resistance R.

Image of FIG. 4.
FIG. 4.

(a) Schematic of the ratchet cell sorter. (b) A mixture of leukocytes (blue cells) and UC13 cells (red cells) enters the bottom row of the sorting region. (c) UC13 cells get trapped at the lower funnel rows before the critical 6 m cut-off. (d) Leukocytes travel past the cut-off, ratcheting even further, and are eventually extracted into a separate outlet.

Image of FIG. 5.
FIG. 5.

After a sorting cycle, smaller, more deformable leukocytes stained in blue travel to the higher funnel rows shown in (a) brightfield, (b) green fluorescence, and (c) blue fluorescence. Larger and more rigid UC13 cancer cells are retained near the bottom, shown in (d) brightfield, (e) green, and (f) blue.

Image of FIG. 6.
FIG. 6.

Capture yields and enrichment ratio of the ratchet cell sorter at various UC13 doping concentrations.

Image of FIG. 7.
FIG. 7.

Capture yield, enrichment, and purity for samples with UC13 cells doped at 1:100 and 1:1000 concentrations.


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Table I.

Flow ratios and overall fluid removal performance of concentrator system.


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Scitation: Highly selective biomechanical separation of cancer cells from leukocytes using microfluidic ratchets and hydrodynamic concentrator