High-Throughput Microfluidic Labyrinth for the Label-free Isolation of Circulating Tumor Cells

被引:91
作者
Lin, Eric [1 ,4 ,6 ]
Rivera-Baez, Lianette [1 ,4 ,6 ]
Fouladdel, Shamileh [2 ,4 ,6 ]
Yoon, Hyeun Joong [1 ,4 ,6 ]
Guthrie, Stephanie [1 ,4 ,6 ]
Wieger, Jacob [1 ,4 ,6 ]
Deol, Yadwinder [2 ,4 ]
Keller, Evan [2 ,4 ,6 ]
Sahai, Vaibhav [2 ,4 ,6 ]
Simeone, Diane M. [3 ,4 ,5 ]
Burness, Monika L. [2 ,4 ]
Azizi, Ebrahim [2 ,4 ,6 ]
Wicha, Max S. [2 ,4 ,6 ]
Nagrath, Sunitha [1 ,4 ,6 ]
机构
[1] Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Translat Oncol Program, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Biointerfaces Inst, Ann Arbor, MI 48109 USA
关键词
STEM-CELLS; PANCREATIC-CANCER; POISEUILLE FLOW; SEPARATION; CAPTURE; RELEASE; BLOOD; PLASTICITY; MUTATIONS; PARTICLE;
D O I
10.1016/j.cels.2017.08.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We present "Labyrinth,'' a label-free microfluidic device to isolate circulating tumor cells (CTCs) using the combination of long loops and sharp corners to focus both CTCs and white blood cells (WBCs) at a high throughput of 2.5 mL/min. The high yield (>90%) and purity (600 WBCs/mL) of Labyrinth enabled us to profile gene expression in CTCs. As proof of principle, we used previously established cancer stem cell gene signatures to profile single cells isolated from the blood of breast cancer patients. We observed heterogeneous subpopulations of CTCs expressing genes for stem cells, epithelial cells, mesenchymal cells, and cells transitioning between epithelial and mesenchymal. Labyrinth offers a cell-surface marker-independent single-cell isolation platform to study heterogeneous CTC subpopulations.
引用
收藏
页码:295 / +
页数:14
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