Isolation and retrieval of circulating tumor cells using centrifugal forces

被引:601
作者
Hou, Han Wei [1 ,2 ]
Warkiani, Majid Ebrahimi [2 ]
Khoo, Bee Luan [3 ]
Li, Zi Rui [2 ]
Soo, Ross A. [4 ,5 ,6 ]
Tan, Daniel Shao-Weng [7 ]
Lim, Wan-Teck [7 ]
Han, Jongyoon [1 ,2 ,8 ]
Bhagat, Ali Asgar S. [2 ]
Lim, Chwee Teck [2 ,3 ,9 ,10 ]
机构
[1] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA
[2] SMART, BioSyst & Micromech BioSyM IRG, Singapore, Singapore
[3] Natl Univ Singapore, Mechanobiol Inst, Singapore 117548, Singapore
[4] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore
[5] Natl Univ Singapore Hosp, Dept Haematol Oncol, Singapore 117548, Singapore
[6] Univ Western Australia, Dept Surg, Nedlands, WA 6009, Australia
[7] Natl Canc Ctr Singapore, Singapore, Singapore
[8] MIT, Dept Biol Engn, Cambridge, MA 02139 USA
[9] Natl Univ Singapore, Dept Bioengn, Singapore 117548, Singapore
[10] Natl Univ Singapore, Dept Mech Engn, Singapore 117548, Singapore
来源
SCIENTIFIC REPORTS | 2013年 / 3卷
基金
新加坡国家研究基金会; 英国医学研究理事会;
关键词
EPITHELIAL-MESENCHYMAL TRANSITION; METASTATIC BREAST-CANCER; PERIPHERAL-BLOOD; STEM-CELL; MICROFLUIDICS; ENUMERATION; MICRODEVICE; PROGRESSION; SEPARATION; SURVIVAL;
D O I
10.1038/srep01259
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Presence and frequency of rare circulating tumor cells (CTCs) in bloodstreams of cancer patients are pivotal to early cancer detection and treatment monitoring. Here, we use a spiral microchannel with inherent centrifugal forces for continuous, size-based separation of CTCs from blood (Dean Flow Fractionation (DFF)) which facilitates easy coupling with conventional downstream biological assays. Device performance was optimized using cancer cell lines (> 85% recovery), followed by clinical validation with positive CTCs enumeration in all samples from patients with metastatic lung cancer (n = 20; 5-88 CTCs per mL). The presence of CD133(+) cells, a phenotypic marker characteristic of stem-like behavior in lung cancer cells was also identified in the isolated subpopulation of CTCs. The spiral biochip identifies and addresses key challenges of the next generation CTCs isolation assay including antibody independent isolation, high sensitivity and throughput (3 mL/hr); and single-step retrieval of viable CTCs.
引用
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页数:8
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