Issue 20, 2019

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

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

Supplementary files

Article information

Article type
Paper
Submitted
17 Jūn. 2019
Accepted
06 Sept. 2019
First published
20 Sept. 2019
This article is Open Access
Creative Commons BY-NC license

Lab Chip, 2019,19, 3427-3437

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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