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Issue 11, 2011
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Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation

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Abstract

Blood is a highly complex bio-fluid with cellular components making up >40% of the total volume, thus making its analysis challenging and time-consuming. In this work, we introduce a high-throughput size-based separation method for processing diluted blood using inertial microfluidics. The technique takes advantage of the preferential cell focusing in high aspect-ratio microchannels coupled with pinched flow dynamics for isolating low abundance cells from blood. As an application of the developed technique, we demonstrate the isolation of cancer cells (circulating tumor cells (CTCs)) spiked in blood by exploiting the difference in size between CTCs and hematologic cells. The microchannel dimensions and processing parameters were optimized to enable high throughput and high resolution separation, comparable to existing CTC isolation technologies. Results from experiments conducted with MCF-7 cells spiked into whole blood indicate >80% cell recovery with an impressive 3.25 × 105 fold enrichment over red blood cells (RBCs) and 1.2 × 104 fold enrichment over peripheral blood leukocytes (PBL). In spite of a 20× sample dilution, the fast operating flow rate allows the processing of ∼108cells min−1 through a single microfluidic device. The device design can be easily customized for isolating other rare cells from blood including peripheral blood leukocytes and fetal nucleated red blood cells by simply varying the ‘pinching’ width. The advantage of simple label-free separation, combined with the ability to retrieve viable cells post enrichment and minimal sample pre-processing presents numerous applications for use in clinical diagnosis and conducting fundamental studies.

Graphical abstract: Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation

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Publication details

The article was received on 26 Nov 2010, accepted on 16 Mar 2011 and first published on 19 Apr 2011


Article type: Paper
DOI: 10.1039/C0LC00633E
Citation: Lab Chip, 2011,11, 1870-1878
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    Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation

    A. A. S. Bhagat, H. W. Hou, L. D. Li, C. T. Lim and J. Han, Lab Chip, 2011, 11, 1870
    DOI: 10.1039/C0LC00633E

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