Sarioglu, A. FatihAceto, NicolaKojic, NikolaDonaldson, Maria C.Zeinali, MahnazHamza, BasharEngstrom, AmandaZhu, HuiliSundaresan, Tilak K.Miyamoto, DavidLuo, XiBardia, AdityaWittner, BenRamaswamy, SridharShioda, ToshiTing, DavidStott, ShannonKapur, RaviMaheswaran, ShyamalaHaber, DanielToner, Mehmet2016-02-012015Sarioglu, A. F., N. Aceto, N. Kojic, M. C. Donaldson, M. Zeinali, B. Hamza, A. Engstrom, et al. 2015. “A microfluidic device for label-free, physical capture of circulating tumor cell-clusters.” Nature methods 12 (7): 685-691. doi:10.1038/nmeth.3404. http://dx.doi.org/10.1038/nmeth.3404.1548-7091http://nrs.harvard.edu/urn-3:HUL.InstRepos:24983852Cancer 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 primarily to isolate single CTCs, and while CTC-clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here, we developed a microchip technology (Cluster-Chip) specifically designed to capture CTC-clusters independent 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 identify CTC-clusters in 30–40% of patients with metastatic cancers of the breast, prostate and melanoma. RNA sequencing of CTC-clusters confirms their tumor origin and identifies leukocytes within the clusters as tissue-derived macrophages. Together, the development of a device for efficient capture of CTC-clusters will enable detailed characterization of their biological properties and role in cancer metastasis.en-USJournal Article2016-02-0110.1038/nmeth.3404