4.8 Article

A microfluidic device for label-free, physical capture of circulating tumor cell clusters

Journal

NATURE METHODS
Volume 12, Issue 7, Pages 685-+

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.3404

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Funding

  1. Swiss National Science Foundation
  2. Human Frontiers Science Program
  3. US National Institutes of Health (NIH) P41 Resource Center
  4. NIH National Institute of Biomedical Imaging and Bioengineering Quantum Grant
  5. Stand Up to Cancer
  6. Howard Hughes Medical Institute
  7. Prostate Cancer Foundation
  8. Charles Evans Foundation
  9. Johnson and Johnson

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Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.

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