Home LiteratureArticle Details
PMID: 25984697 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature methods ·Vol. 12 ·No. 7 ·2015-07-00 ·Pages 685-91

Sarioglu AF, Aceto N, Kojic N, Donaldson MC, Zeinali M, Hamza B, Engstrom A, Zhu H, Sundaresan TK, Miyamoto DT, Luo X, Bardia A, Wittner BS, Ramaswamy S, Shioda T, Ting DT, Stott SL, Kapur R, Maheswaran S, Haber DA, Toner M

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.

MeSH Terms
Breast Neoplasms/pathology Cell Line, Tumor Female Humans Immunohistochemistry Male Microfluidic Analytical Techniques Neoplastic Cells, Circulating Prostatic Neoplasms/pathology Sequence Analysis, RNA
Authors & Affiliations
21 authors, click to expand affiliations / ORCID
Sarioglu A Fatih
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.
Aceto Nicola
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.
Kojic Nikola
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.
Donaldson Maria C
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Zeinali Mahnaz
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.
Hamza Bashar
Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Engstrom Amanda
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Zhu Huili
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Sundaresan Tilak K
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Miyamoto David T
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.
Luo Xi
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Bardia Aditya
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.
Wittner Ben S ORCID
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ramaswamy Sridhar
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.
Shioda Toshi
Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Ting David T
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.
Stott Shannon L
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.
Kapur Ravi
Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Maheswaran Shyamala
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.
Haber Daniel A
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.
Toner Mehmet
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.
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Article Info
Journal
Nature methods
Abbr.
Nat Methods
ISSN
1548-7105
DOI
10.1038/nmeth.3404
Published
2015-07-00
Epub
2015-00-18
Pages
685-91
Language
English
Region
United States
NLM ID
101215604
PMCID
PMC4490017
Subset
IM
Grants
NIBIB NIH HHS · U01 EB012493 · United States
NIBIB NIH HHS · R01 EB008047 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · K12 CA087723 · United States
NIBIB NIH HHS · P41 EB002503 · United States
Databases
GEO
GSE67939
External Links
PubMed source DOI: 10.1038/nmeth.3404 PMC Full Text View journal details
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