title: A microfluidic device for label-free, physical capture of circulating tumor cell clusters.
abstract: 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.
authors.affiliation: 1] Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: A Fatih
authors.initials: AF
authors.lastname: Sarioglu
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Aceto
authors.affiliation: 1] Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kojic
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Donaldson
authors.affiliation: 1] Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Zeinali
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bashar
authors.initials: B
authors.lastname: Hamza
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Engstrom
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Huili
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Tilak K
authors.initials: TK
authors.lastname: Sundaresan
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Miyamoto
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Luo
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bardia
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ben S
authors.identifier: 0000000156579849
authors.initials: BS
authors.lastname: Wittner
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Ramaswamy
authors.affiliation: Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Toshi
authors.initials: T
authors.lastname: Shioda
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Ting
authors.affiliation: 1] Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Stott
authors.affiliation: Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kapur
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Shyamala
authors.initials: S
authors.lastname: Maheswaran
authors.affiliation: 1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Howard Hughes Medical Institute, Chevy Chase, Maryland, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Haber
authors.affiliation: 1] Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046210:Microfluidic Analytical Techniques; D009360:Neoplastic Cells, Circulating; D011471:Prostatic Neoplasms / Q000473:pathology; D017423:Sequence Analysis, RNA