Highly-sensitive capture of circulating tumor cells using microellipse filters

被引:53
作者
Chen, Hongmei [1 ,2 ]
Cao, Baoshan [3 ]
Sun, Bo [1 ]
Cao, Yapeng [1 ]
Yang, Ke [4 ]
Lin, Yu-Sheng [2 ]
Chen, Hongda [1 ]
机构
[1] Chinese Acad Sci, Inst Semicond, Beijing 100083, Peoples R China
[2] Chinese Acad Sci, Suzhou Inst Nanotech & Nano Bion, Div Nanob Res, Suzhou 215123, Jiangsu, Peoples R China
[3] Peking Univ, Hosp 3, Dept Chemotherapy & Radiat Sickness, Beijing 100191, Peoples R China
[4] Univ Massachusetts Lowell, Dept Phys, Lowell, MA 01854 USA
基金
中国国家自然科学基金;
关键词
MICROFLUIDIC DEVICE; CANCER-PATIENTS; LABEL-FREE; MICROCHIP;
D O I
10.1038/s41598-017-00232-6
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
Circulating tumor cells (CTCs) detection, enumeration and characterization with microfluidic chips has critical significance in cancer prognosis offering a non-invasive "liquid biopsy". Based on physical differences of size and deformability, we explore micro-ellipse filters consisting of microfuidic slits in series gradually narrowed. Slender tunnels sensitively capture tumor cells with slim chance to escape. Tumor cells could reside at capture sites organized by arrays of micro-ellipse microposts enduring less stress. Circular elliptical microstructures produce smooth flow minimally reducing any damage. "Air Suction" could extremely shorten capture. Capture efficiency comes out to be a robust yield of 90% and percentage obeys Gaussian distribution at various stages. With rare number accurately enumerated, micro-Ellipse filters have been tested high efficiently capturing tumor cells in both whole and lysed blood. To clinically validate the device, the microfluidic chip was utilized to identify and capture CTCs from metastatic breast, colon and non-small-cell lung (NSCLC) cancer patients. CTCs were detected positive in all samples with 4 patients having more than 20 CTCs. Those sensitive results are consistent with theoretical expectation. Efficient micro-ellipse filters enable clinical enumeration of metastasis, on-chip anti-cancer drug responses and biological molecular analysis.
引用
收藏
页数:10
相关论文
共 36 条
[1]   Characterization of ERG, AR and PTEN Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer [J].
Attard, Gerhardt ;
Swermenhuis, Joost F. ;
Olmos, David ;
Reid, Alison H. M. ;
Vickers, Elaine ;
A'Hern, Roger ;
Levink, Rianne ;
Coumans, Frank ;
Moreira, Joana ;
Riisnaes, Ruth ;
Oommen, Nikhil Babu ;
Hawche, George ;
Jameson, Charles ;
Thompson, Emilda ;
Sipkema, Ronald ;
Carden, Craig P. ;
Parker, Christopher ;
Dearnaley, David ;
Kaye, Stan B. ;
Cooper, Colin S. ;
Molina, Arturo ;
Cox, Michael E. ;
Terstappen, Leon W. M. M. ;
de Bono, Johann S. .
CANCER RESEARCH, 2009, 69 (07) :2912-2918
[2]   High purity microfluidic sorting and analysis of circulating tumor cells: towards routine mutation detection [J].
Autebert, Julien ;
Coudert, Benoit ;
Champ, Jerome ;
Saias, Laure ;
Guneri, Ezgi Tulukcuoglu ;
Lebofsky, Ronald ;
Bidard, Francois-Clement ;
Pierga, Jean-Yves ;
Farace, Francoise ;
Descroix, Stephanie ;
Malaquin, Laurent ;
Viovy, Jean-Louis .
LAB ON A CHIP, 2015, 15 (09) :2090-2101
[3]   Rare cell isolation and profiling on a hybrid magnetic/size-sorting chip [J].
Chung, Jaehoon ;
Issadore, David ;
Ullal, Adeeti ;
Lee, Kyungheon ;
Weissleder, Ralph ;
Lee, Hakho .
BIOMICROFLUIDICS, 2013, 7 (05)
[4]   Circulating tumor cells: A novel prognostic factor for newly diagnosed metastatic breast cancer [J].
Cristofanilli, M ;
Hayes, DF ;
Budd, GT ;
Ellis, MJ ;
Stopeck, A ;
Reuben, JM ;
Doyle, GV ;
Matera, J ;
Allard, WJ ;
Miller, MC ;
Fritsche, HA ;
Hortobagyi, GN ;
Terstappen, LWMM .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (07) :1420-1430
[5]   Circulating tumor cells, disease progression, and survival in metastatic breast cancer [J].
Cristofanilli, Massimo .
SEMINARS IN ONCOLOGY, 2006, 33 (03) :S9-S14
[6]   Epithelial-mesenchymal transition, cancer stem cells and treatment resistance [J].
Dave, Bhuvanesh ;
Mittal, Vivek ;
Tan, Nicholas M. ;
Chang, Jenny C. .
BREAST CANCER RESEARCH, 2012, 14 (01)
[7]   Microfluidics and Circulating Tumor Cells [J].
Dong, Yi ;
Skelley, Alison M. ;
Merdek, Keith D. ;
Sprott, Kam M. ;
Jiang, Chunsheng ;
Pierceall, William E. ;
Lin, Jessie ;
Stocum, Michael ;
Carney, Walter P. ;
Smirnov, Denis A. .
JOURNAL OF MOLECULAR DIAGNOSTICS, 2013, 15 (02) :149-157
[8]   Clinical significance of circulating tumor cells detected by an invasion assay in peripheral blood of patients with ovarian cancer [J].
Fan, Tina ;
Zhao, Qiang ;
Chen, John J. ;
Chen, Wen-Tien ;
Pearl, Michael L. .
GYNECOLOGIC ONCOLOGY, 2009, 112 (01) :185-191
[9]   Development of an Automated and Sensitive Microfluidic Device for Capturing and Characterizing Circulating Tumor Cells (CTCs) from Clinical Blood Samples [J].
Gogoi, Priya ;
Sepehri, Saedeh ;
Zhou, Yi ;
Gorin, Michael A. ;
Paolillo, Carmela ;
Capoluongo, Ettore ;
Gleason, Kyle ;
Payne, Austin ;
Boniface, Brian ;
Cristofanilli, Massimo ;
Morgan, Todd M. ;
Fortina, Paolo ;
Pienta, Kenneth J. ;
Handique, Kalyan ;
Wang, Yixin .
PLOS ONE, 2016, 11 (01)
[10]   Micro-NMR for Rapid Molecular Analysis of Human Tumor Samples [J].
Haun, Jered B. ;
Castro, Cesar M. ;
Wang, Rui ;
Peterson, Vanessa M. ;
Marinelli, Brett S. ;
Lee, Hakho ;
Weissleder, Ralph .
SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (71)