Integrated Microfluidic Chip for Efficient Isolation and Deformability Analysis of Circulating Tumor Cells

被引:36
作者
Liu, Zongbin [1 ,2 ,5 ]
Chen, Rui [1 ,2 ,3 ,6 ]
Li, Ying [1 ,2 ]
Liu, Jianqiao [3 ]
Wang, Ping [4 ,7 ]
Xia, Xuefeng [3 ]
Qin, Lidong [1 ,2 ]
机构
[1] Houston Methodist Res Inst, Dept Nanomed, Houston, TX 77030 USA
[2] Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA
[3] Guangzhou Med Univ, Affiliated Hosp 3, Guangzhou 510150, Guangdong, Peoples R China
[4] Houston Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA
[5] Zigzag Biotechnol Co Ltd, Shenzhen 518000, Peoples R China
[6] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Guangzhou 510000, Guangdong, Peoples R China
[7] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
基金
中国国家自然科学基金;
关键词
circulating tumor cells; deformability; deterministic lateral displacement; microfluidic integrated chip; SEPARATION; PROGRESSION; METASTASES; DIVERSITY; STIFFNESS;
D O I
10.1002/adbi.201800200
中图分类号
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号
0805 ; 080501 ; 080502 ;
摘要
Efficient isolation and downstream analysis of circulating tumor cells (CTCs) beyond counting is challenging. Here, an integrated microfluidic chip for efficient isolation and deformability analysis of CTCs is reported. The microfluidic chip integrates two modules: one module is two mirrored deterministic lateral displacement (DLD) arrays for the depletion of blood cells; the other module is another DLD array with an increasing tilt angle for CTCs separation based on size and deformability. The chip allows continuous isolation of CTCs with >90% capture yield and >50% capture purity at a throughput of 12 mL h(-1). Results show that the captured cancer cells maintain good viability. Downstream deformability analysis validates that invasive MDA-MB-231 cells are more flexible than noninvasive MCF-7 cells. The deformability of CTCs isolated from cancer patient samples is highly heterogeneous. The implementation of cell deformability analysis integrated with microfluidics extends the laboratory capability beyond simple counting of CTCs.
引用
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页数:8
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