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Issue 20, 2019
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Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

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Abstract

Isolation and analysis of circulating tumor cells (CTCs) from blood samples present exciting opportunities for basic cancer research and personalized treatment of the disease. While microchip-based negative CTC enrichment offers both sensitive microfluidic cell screening and unbiased selection, conventional microchips are inherently limited by their capacity to deplete a large number of normal blood cells. In this paper, we use 3D printing to create a monolithic device that combines immunoaffinity-based microfluidic cell capture and a commercial membrane filter for negative enrichment of CTCs directly from whole blood. In our device, stacked layers of chemically-functionalized microfluidic channels capture millions of white blood cells (WBCs) in parallel without getting saturated and the leuko-depleted blood is post-filtered with a 3 μm-pore size membrane filter to eliminate anucleated blood cells. This hybrid negative enrichment approach facilitated direct extraction of viable CTCs off the chip on a membrane filter for downstream analysis. Immunofluorescence imaging of enriched cells showed ∼90% tumor cell recovery rate from simulated samples spiked with prostate, breast or ovarian cancer cells. We also demonstrated the feasibility of our approach for processing clinical samples by isolating prostate cancer CTCs directly from a 10 mL whole blood sample.

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

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Publication details

The article was received on 17 Jun 2019, accepted on 06 Sep 2019 and first published on 20 Sep 2019


Article type: Paper
DOI: 10.1039/C9LC00575G
Lab Chip, 2019,19, 3427-3437
  • Open access: Creative Commons BY-NC license
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    Hybrid negative enrichment of circulating tumor cells from whole blood in a 3D-printed monolithic device

    C. Chu, R. Liu, T. Ozkaya-Ahmadov, M. Boya, B. E. Swain, J. M. Owens, E. Burentugs, M. A. Bilen, J. F. McDonald and A. F. Sarioglu, Lab Chip, 2019, 19, 3427
    DOI: 10.1039/C9LC00575G

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