Characterization of microfluidic shear-dependent epithelial cell adhesion molecule immunocapture and enrichment of pancreatic cancer cells from blood cells with dielectrophoresis

被引:20
|
作者
Huang, Chao [1 ]
Smith, James P. [2 ]
Saha, Trisha N. [3 ]
Rhim, Andrew D. [3 ]
Kirby, Brian J. [2 ,4 ]
机构
[1] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA
[2] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA
[3] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA
[4] Weill Cornell Med Coll, Div Hematol & Med Oncol, Dept Med, New York, NY 10065 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
CIRCULATING TUMOR-CELLS; DIELECTRIC-PROPERTIES; ELECTROROTATION; CAPTURE; EPCAM; FLOW; OVEREXPRESSION; ANTIBODIES; SEPARATION; RNA;
D O I
10.1063/1.4890466
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Current microfluidic techniques for isolating circulating tumor cells (CTCs) from cancer patient blood are limited by low capture purity, and dielectrophoresis (DEP) has the potential to complement existing immunocapture techniques to improve capture performance. We present a hybrid DEP and immunocapture Hele-Shaw flow cell to characterize DEP's effects on immunocapture of pancreatic cancer cells (Capan-1, PANC-1, and BxPC-3) and peripheral blood mononuclear cells (PBMCs) with an anti-EpCAM (epithelial cell adhesion molecule) antibody. By carefully specifying the applied electric field frequency, we demonstrate that pancreatic cancer cells are attracted to immunocapture surfaces by positive DEP whereas PBMCs are repelled by negative DEP. Using an exponential capture model to interpret our capture data, we show that immunocapture performance is dependent on the applied DEP force sign and magnitude, cell surface EpCAM expression level, and shear stress experienced by cells flowing in the capture device. Our work suggests that DEP can not only repel contaminating blood cells but also enhance capture of cancer cell populations that are less likely to be captured by traditional immunocapture methods. This combination of DEP and immunocapture techniques to potentially increase CTC capture purity can facilitate subsequent biological analyses of captured CTCs and research on cancer metastasis and drug therapies. (C) 2014 AIP Publishing LLC.
引用
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页数:13
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