All-in-One Centrifugal Microfluidic Device for Size-Selective Circulating Tumor Cell Isolation with High Purity

被引:105
作者
Lee, Ada [1 ]
Park, Juhee [1 ]
Lim, Minji [1 ]
Sunkara, Vijaya [1 ]
Kim, Shine Young [2 ]
Kim, Gwang Ha [3 ]
Kim, Mi-Hyun [3 ]
Cho, Yoon-Kyoung [1 ,4 ]
机构
[1] Ulsan Natl Inst Sci & Technol UNIST, Dept Biomed Engn, Ulsan 689798, South Korea
[2] Pusan Natl Univ, Sch Med, Dept Clin Lab Med, Pusan 602739, South Korea
[3] Pusan Natl Univ, Sch Med, Dept Internal Med, Pusan 602739, South Korea
[4] Inst Basic Sci, Ctr Soft & Living Matter, Ulsan 689798, South Korea
基金
新加坡国家研究基金会;
关键词
ISOLATION PLATFORM; WHOLE-BLOOD; A-DISC; LAB; ENUMERATION; ENRICHMENT; CAPTURE;
D O I
10.1021/ac5035049
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Circulating tumor cells (CTCs) have gained increasing attention owing to their roles in cancer recurrence and progression. Due to the rarity of CTCs in the bloodstream, an enrichment process is essential for effective target cell characterization. However, in a typical pressure-driven micro-fluidic system, the enrichment process generally requires complicated equipment and long processing times. Furthermore, the commonly used immunoaffinity-based positive selection method is limited, as its recovery rate relies on EpCAM expression of target CTCs, which shows heterogeneity among cell types. Here, we propose a centrifugal-force-based size-selective CTC isolation platform that can isolate and enumerate C'TCs from whole blood within 30 s with high purity. The device was validated using the MCF-7 breast cancer cell line spiked in phosphate-buffered saline and whole blood, and an average capture efficiency of 61% was achieved, which is typical for size-based filtration. The capture efficiency for whole blood samples varied from 44% to 84% under various flow conditions and dilution factors. Under the optimized operating conditions, a few hundred white blood cells per 1 mL of whole blood were captured, representing a 20-fold decrease compared to those obtained using a commercialized size-based CTC isolation device. In clinical validation, normalized CTC counts varied from 10 to 60 per 7.5 mL of blood from gastric and lung cancer patients, yielding a detection rate of 50% and 38%, respectively. Overall, our CTC isolation device enables rapid and label-free isolation of CTCs with high purity, which should greatly improve downstream molecular analyses of captured CTCs.
引用
收藏
页码:11349 / 11356
页数:8
相关论文
共 35 条
[1]   Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor [J].
Adams, Andre A. ;
Okagbare, Paul I. ;
Feng, Juan ;
Hupert, Matuesz L. ;
Patterson, Don ;
Goettert, Jost ;
McCarley, Robin L. ;
Nikitopoulos, Dimitris ;
Murphy, Michael C. ;
Soper, Steven A. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (27) :8633-8641
[2]   The systematic study of circulating tumor cell isolation using lithographic microfilters [J].
Adams, Daniel L. ;
Zhu, Peixuan ;
Makarova, Olga V. ;
Martin, Stuart S. ;
Charpentier, Monica ;
Chumsri, Saranya ;
Li, Shuhong ;
Amstutz, Platte ;
Tang, Cha-Mei .
RSC ADVANCES, 2014, 4 (09) :4334-4342
[3]   Filtration Parameters Influencing Circulating Tumor Cell Enrichment from Whole Blood [J].
Coumans, Frank A. W. ;
van Dalum, Guus ;
Beck, Markus ;
Terstappen, Leon W. M. M. .
PLOS ONE, 2013, 8 (04)
[4]   Filter Characteristics Influencing Circulating Tumor Cell Enrichment from Whole Blood [J].
Coumans, Frank A. W. ;
van Dalum, Guus ;
Beck, Markus ;
Terstappen, Leon W. M. M. .
PLOS ONE, 2013, 8 (04)
[5]   Circulating tumor cells: the Grand Challenge [J].
den Toonder, Jaap .
LAB ON A CHIP, 2011, 11 (03) :375-377
[6]  
Desitter I, 2011, ANTICANCER RES, V31, P427
[7]   Detecting Circulating Tumor Cells: Current Challenges and New Trends [J].
Hong, Bin ;
Zu, Youli .
THERANOSTICS, 2013, 3 (06) :377-394
[8]   Microchip-based immunomagnetic detection of circulating tumor cells [J].
Hoshino, Kazunori ;
Huang, Yu-Yen ;
Lane, Nancy ;
Huebschman, Michael ;
Uhr, Jonathan W. ;
Frenkel, Eugene P. ;
Zhang, Xiaojing .
LAB ON A CHIP, 2011, 11 (20) :3449-3457
[9]   Microcavity Array System for Size-Based Enrichment of Circulating Tumor Cells from the Blood of Patients with Small-Cell Lung Cancer [J].
Hosokawa, Masahito ;
Yoshikawa, Takayuki ;
Negishi, Ryo ;
Yoshino, Tomoko ;
Koh, Yasuhiro ;
Kenmotsu, Hirotsugu ;
Naito, Tateaki ;
Takahashi, Toshiaki ;
Yamamoto, Nobuyuki ;
Kikuhara, Yoshihito ;
Kanbara, Hisashige ;
Tanaka, Tsuyoshi ;
Yamaguchi, Ken ;
Matsunaga, Tadashi .
ANALYTICAL CHEMISTRY, 2013, 85 (12) :5692-5698
[10]   Isolation and retrieval of circulating tumor cells using centrifugal forces [J].
Hou, Han Wei ;
Warkiani, Majid Ebrahimi ;
Khoo, Bee Luan ;
Li, Zi Rui ;
Soo, Ross A. ;
Tan, Daniel Shao-Weng ;
Lim, Wan-Teck ;
Han, Jongyoon ;
Bhagat, Ali Asgar S. ;
Lim, Chwee Teck .
SCIENTIFIC REPORTS, 2013, 3