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Small. 2018 Aug;14(32):e1801131. doi: 10.1002/smll.201801131. Epub 2018 Jul 3.

Circulating Tumor Cell Phenotyping via High-Throughput Acoustic Separation.

Author information

1
Department of Mechanical Engineering and Material Science, Duke University, Durham, NC, 27708, USA.
2
Department of Engineering Science and Mechanics, The Pennsylvania State University, University Park, PA, 16802, USA.
3
Duke Cancer Institute and Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA.
4
Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV, 26506, USA.
5
Department of Pharmacology & Chemical Biology, Magee-Women's Research Institute, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
6
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
7
Nanyang Technological University, 50 Nanyang Avenue, Main Campus, Singapore, 639798, Singapore.

Abstract

The study of circulating tumor cells (CTCs) offers pathways to develop new diagnostic and prognostic biomarkers that benefit cancer treatments. In order to fully exploit and interpret the information provided by CTCs, the development of a platform is reported that integrates acoustics and microfluidics to isolate rare CTCs from peripheral blood in high throughput while preserving their structural, biological, and functional integrity. Cancer cells are first isolated from leukocytes with a throughput of 7.5 mL h-1 , achieving a recovery rate of at least 86% while maintaining the cells' ability to proliferate. High-throughput acoustic separation enables statistical analysis of isolated CTCs from prostate cancer patients to be performed to determine their size distribution and phenotypic heterogeneity for a range of biomarkers, including the visualization of CTCs with a loss of expression for the prostate specific membrane antigen. The method also enables the isolation of even rarer, but clinically important, CTC clusters.

KEYWORDS:

acoustofluidics; cancer phenotyping; circulating tumor cells; high-throughput separation; microfluidics

PMID:
29968402
PMCID:
PMC6105522
[Available on 2019-02-01]
DOI:
10.1002/smll.201801131

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