Continuous Separation of Circulating Tumor Cells from Whole Blood Using a Slanted Weir Microfluidic Device

The separation of circulating tumor cells (CTCs) from the peripheral blood is an important issue that has been highlighted because of their high clinical potential. However, techniques that depend solely on tumor-specific surface molecules or just the larger size of CTCs are limited by tumor heterogeneity. Here, we present a slanted weir microfluidic device that utilizes the size and deformability of CTCs to separate them from the unprocessed whole blood. By testing its ability using a highly invasive breast cancer cell line, our device achieved a 97% separation efficiency, while showing an 8-log depletion of erythrocytes and 5.6-log depletion of leukocytes. We also developed an image analysis tool that was able to characterize the various morphologies and differing deformability of the separating cells. From the results, we believe our system possesses a high potential for liquid biopsy, aiding future cancer research.

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Enrichment of Circulating Tumor Cells from Whole Blood Using a Microfluidic Device for Sequential Physical and Magnetophoretic Separations

Micromachines ◽

10.3390/mi11050481 ◽

2020 ◽

Vol 11 (5) ◽

pp. 481 ◽

Cited By ~ 2

Author(s):

Jusin Lee ◽

Onejae Sul ◽

Seung-Beck Lee

Keyword(s):

Specific Surface ◽

Cancer Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Microfluidic Device ◽

Whole Blood ◽

Blood Cells ◽

Magnetic Beads ◽

Separation Efficiency ◽

White Blood Cells

Based on their high clinical potential, the isolation and enrichment of rare circulating tumor cells (CTCs) from peripheral blood cells has been widely investigated. There have been technical challenges with CTC separation methods using solely cancer-specific surface molecules or just using physical properties of CTCs, as they may suffer from heterogeneity or lack of specificity from overlapping physical characteristics with leukocytes. Here, we integrated an immunomagnetic-based negative enrichment method that utilizes magnetic beads attached to leukocyte-specific surface antigens, with a physical separation method that utilizes the distinct size and deformability of CTCs. By manipulating the pressure distribution throughout the device and balancing the drag and magnetic forces acting on the magnetically labeled white blood cells (WBCs), the sequential physical and magnetophoretic separations were optimized to isolate intact cancer cells, regardless of heterogeneity from whole blood. Using a breast cancer cell line in whole blood, we achieved 100% separation efficiency for cancer cells and an average of 97.2% for WBCs, which resulted in a 93.3% average separation purity. The experimental results demonstrated that our microfluidic device can be a promising candidate for liquid biopsy and can be a vital tool for aiding future cancer research.

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Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

Lab on a Chip ◽

10.1039/c9lc00575g ◽

2019 ◽

Vol 19 (20) ◽

pp. 3427-3437 ◽

Cited By ~ 6

Author(s):

Chia-Heng Chu ◽

Ruxiu Liu ◽

Tevhide Ozkaya-Ahmadov ◽

Mert Boya ◽

Brandi E. Swain ◽

...

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Microfluidic Device ◽

Whole Blood ◽

3D Printed

A monolithic 3D-printed microfluidic device integrated with stacked layers of functionalized leukodepletion channels and microfiltration for the negative enrichment of circulating tumor cells directly from clinically relevant volumes of whole blood.

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/30409968u ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/30409968 ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/30409967u ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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Molecular in vitro diagnostic examinations - Specifications for pre-examination processes for circulating tumor cells (CTCs) in venous whole blood

10.3403/pdcents17390 ◽

2020 ◽

Keyword(s):

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

In Vitro Diagnostic

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A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells

10.1115/fedsm2021-65766 ◽

2021 ◽

Author(s):

Jeff Darabi ◽

Joseph Schober

Keyword(s):

Cancer Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Blood ◽

Peripheral Blood ◽

Automated Image Analysis ◽

Rare Cancer ◽

On Chip ◽

Chip Analysis ◽

Selection Of

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.

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