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

A Fatih Sarioglu; Nicola Aceto; Nikola Kojic; Maria C Donaldson; Mahnaz Zeinali; Bashar Hamza; Amanda Engstrom; Huili Zhu; Tilak K Sundaresan; David T Miyamoto; Xi Luo; Aditya Bardia; Ben S Wittner; Sridhar Ramaswamy; Toshi Shioda; David T Ting; Shannon L Stott; Ravi Kapur; Shyamala Maheswaran; Daniel A Haber; Mehmet Toner

doi:10.1038/nmeth.3404

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

Nat Methods. 2015 Jul;12(7):685-91. doi: 10.1038/nmeth.3404. Epub 2015 May 18.

Authors

A Fatih Sarioglu¹, Nicola Aceto², Nikola Kojic³, Maria C Donaldson⁴, Mahnaz Zeinali⁵, Bashar Hamza⁶, Amanda Engstrom⁴, Huili Zhu⁴, Tilak K Sundaresan⁴, David T Miyamoto⁷, Xi Luo⁴, Aditya Bardia², Ben S Wittner⁴, Sridhar Ramaswamy², Toshi Shioda⁴, David T Ting², Shannon L Stott⁸, Ravi Kapur⁶, Shyamala Maheswaran⁹, Daniel A Haber¹⁰, Mehmet Toner³

Affiliations

¹ 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.
² 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 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.
⁴ Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁵ 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.
⁶ Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / pathology
Cell Line, Tumor
Female
Humans
Immunohistochemistry
Male
Microfluidic Analytical Techniques*
Neoplastic Cells, Circulating*
Prostatic Neoplasms / pathology
Sequence Analysis, RNA

Associated data

GEO/GSE67939

Abstract

Publication types

MeSH terms

Associated data

Grants and funding