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

Lin, Bill K.; McFaul, Sarah M.; Jin, Chao; Black, Peter C.; Ma, Hongshen

doi:10.1063/1.4812688

Cited by 54 publications

(41 citation statements)

References 47 publications

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“…While for hydrodynamic particle separation, such as pinch-flow based separation, the pinch gap dimension must be designed to be comparable to the particle size so that different sized particles follow different streamlines and hence are separated in the subsequent expansion channel. 54 In comparison to the multi orifice flow fraction (MOFF) structures used for particle separation, 45,46 sharp corner structures used in the current design induce larger streamline curvature, thus generate larger centrifugal forces. At an appropriate flow rate, large particles will be more prone to be focused at the center of the microchannel, while small particles are still focused at two side stream bands (shown in Figure 2).…”

Section: Working Principlementioning

confidence: 99%

Continuous size-based separation of microparticles in a microchannel with symmetric sharp corner structures

Fan

Han

et al. 2014

Biomicrofluidics

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A new microchannel with a series of symmetric sharp corner structures is reported for passive size-dependent particle separation. Micro particles of different sizes can be completely separated based on the combination of the inertial lift force and the centrifugal force induced by the sharp corner structures in the microchannel. At appropriate flow rate and Reynolds number, the centrifugal force effect on large particles, induced by the sharp corner structures, is stronger than that on small particles; hence after passing a series of symmetric sharp corner structures, large particles are focused to the center of the microchannel, while small particles are focused at two particle streams near the two side walls of the microchannel. Particles of different sizes can then be completely separated. Particle separation with this device was demonstrated using 7.32 μm and 15.5 μm micro particles. Experiments show that in comparison with the prior multi-orifice flow fractionation microchannel and multistage-multiorifice flow fractionation microchannel, this device can completely separate two-size particles with narrower particle stream band and larger separation distance between particle streams. In addition, it requires no sheath flow and complex multi-stage separation structures, avoiding the dilution of analyte sample and complex operations. The device has potentials to be used for continuous, complete particle separation in a variety of lab-on-a-chip and biomedical applications.

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Section: Working Principlementioning

confidence: 99%

Continuous size-based separation of microparticles in a microchannel with symmetric sharp corner structures

Fan

Han

et al. 2014

Biomicrofluidics

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“…Among the various separation methods that rely on cell physical properties (8)(9)(10)(11), approaches predicated on acoustics offer several unique characteristics (12).…”

mentioning

confidence: 99%

Acoustic separation of circulating tumor cells

Mao

Peng

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

665

479

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Circulating tumor cells (CTCs) are important targets for cancer biology studies. To further elucidate the role of CTCs in cancer metastasis and prognosis, effective methods for isolating extremely rare tumor cells from peripheral blood must be developed. Acousticbased methods, which are known to preserve the integrity, functionality, and viability of biological cells using label-free and contactfree sorting, have thus far not been successfully developed to isolate rare CTCs using clinical samples from cancer patients owing to technical constraints, insufficient throughput, and lack of long-term device stability. In this work, we demonstrate the development of an acoustic-based microfluidic device that is capable of high-throughput separation of CTCs from peripheral blood samples obtained from cancer patients. Our method uses tilted-angle standing surface acoustic waves. Parametric numerical simulations were performed to design optimum device geometry, tilt angle, and cell throughput that is more than 20 times higher than previously possible for such devices. We first validated the capability of this device by successfully separating low concentrations (∼100 cells/mL) of a variety of cancer cells from cell culture lines from WBCs with a recovery rate better than 83%. We then demonstrated the isolation of CTCs in blood samples obtained from patients with breast cancer. Our acoustic-based separation method thus offers the potential to serve as an invaluable supplemental tool in cancer research, diagnostics, drug efficacy assessment, and therapeutics owing to its excellent biocompatibility, simple design, and label-free automated operation while offering the capability to isolate rare CTCs in a viable state.circulating cancer cells | cell separation | rare-cell sorting | acoustic tweezers | microfluidics

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“…Many types of unique cell sorting and enrichment devices have been devised but they are not usually able to work with unprocessed whole blood [2][3][4][5] . These technologies typically require pre-processed samples and cannot handle the physical properties and complex populations inherent in whole blood [6][7][8][9][10] . They are limited to either diluted 11,12 or lysed blood 13,14 , and in some cases, density based centrifugation to reduce blood complexity and cell-cell interaction [15][16][17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming

et al. 2018

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Analyzing undiluted whole human blood is a challenge due to its complex composition of hematopoietic cellular populations, nucleic acids, metabolites, and proteins. We present a novel multi-functional microfluidic acoustic streaming platform that enables sorting, enrichment and in situ identification of cellular subsets from whole blood. This single device platform, based on lateral cavity acoustic transducers (LCAT), enables (1) the sorting of undiluted donor whole blood into its cellular subsets (platelets, RBCs, and WBCs), (2) the enrichment and retrieval of breast cancer cells (MCF-7) spiked in donor whole blood at rare cell relevant concentrations (10 mL − 1 ), and (3) on-chip immunofluorescent labeling for the detection of specific target cellular populations by their known marker expression patterns. Our approach thus demonstrates a compact system that integrates upstream sample processing with downstream separation/enrichment, to carry out multi-parametric cell analysis for blood-based diagnosis and liquid biopsy blood sampling.

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

Cited by 54 publications

References 47 publications

Continuous size-based separation of microparticles in a microchannel with symmetric sharp corner structures

Continuous size-based separation of microparticles in a microchannel with symmetric sharp corner structures

Acoustic separation of circulating tumor cells

Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming

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