A microfluidic ExoSearch chip for multiplexed exosome detection towards blood-based ovarian cancer diagnosis

被引:565
作者
Zhao, Zheng [1 ,2 ]
Yang, Yang [2 ]
Zeng, Yong [2 ,3 ]
He, Mei [1 ,4 ]
机构
[1] Kansas State Univ, Dept Biol & Agr Engn, Manhattan, KS 66506 USA
[2] Univ Kansas, Dept Chem, Lawrence, KS 66045 USA
[3] Univ Kansas, Ctr Canc, Kansas City, KS 66160 USA
[4] Kansas State Univ, Terry C Johnson Canc Res Ctr, Manhattan, KS 66506 USA
关键词
NANOPARTICLE TRACKING ANALYSIS; DENSITY-GRADIENT SEPARATION; TUMOR-DERIVED EXOSOMES; EXTRACELLULAR VESICLES; CLINICAL UTILITY; MICROVESICLES; ULTRACENTRIFUGATION; BIOGENESIS; PROTEOMICS; PROTOCOL;
D O I
10.1039/c5lc01117e
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Tumor-derived circulating exosomes, enriched with a group of tumor antigens, have been recognized as a promising biomarker source for cancer diagnosis via a less invasive procedure. Quantitatively pinpointing exosome tumor markers is appealing, yet challenging. In this study, we developed a simple microfluidic approach (ExoSearch) which provides enriched preparation of blood plasma exosomes for in situ, multiplexed detection using immunomagnetic beads. The ExoSearch chip offers a robust, continuous-flow design for quantitative isolation and release of blood plasma exosomes in a wide range of preparation volumes (10 mu L to 10 mL). We employed the ExoSearch chip for blood-based diagnosis of ovarian cancer by multiplexed measurement of three exosomal tumor markers (CA-125, EpCAM, CD24) using a training set of ovarian cancer patient plasma, which showed significant diagnostic power (a. u. c. = 1.0, p = 0.001) and was comparable with the standard Bradford assay. This work provides an essentially needed platform for utilization of exosomes in clinical cancer diagnosis, as well as fundamental exosome research.
引用
收藏
页码:489 / 496
页数:8
相关论文
共 53 条
[11]  
Greening DW, 2015, METHODS MOL BIOL, V1295, P179, DOI 10.1007/978-1-4939-2550-6_15
[12]   Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology [J].
He, Mei ;
Crow, Jennifer ;
Roth, Marc ;
Zeng, Yong ;
Godwin, Andrew K. .
LAB ON A CHIP, 2014, 14 (19) :3773-3780
[13]   Tumour-released exosomes and their implications in cancer immunity [J].
Iero, M. ;
Valenti, R. ;
Huber, V. ;
Filipazzi, P. ;
Parmiani, G. ;
Fais, S. ;
Rivoltini, L. .
CELL DEATH AND DIFFERENTIATION, 2008, 15 (01) :80-88
[14]   Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor [J].
Im, Hyungsoon ;
Shao, Huilin ;
Park, Yong Il ;
Peterson, Vanessa M. ;
Castro, Cesar M. ;
Weissleder, Ralph ;
Lee, Hakho .
NATURE BIOTECHNOLOGY, 2014, 32 (05) :490-U219
[15]   Comparative analysis of discrete exosome fractions obtained by differential centrifugation [J].
Jeppesen, Dennis K. ;
Hvam, Michael L. ;
Primdahl-Bengtson, Bjarke ;
Boysen, Anders T. ;
Whitehead, Bradley ;
Dyrskjot, Lars ;
Orntoft, Torben F. ;
Howard, Kenneth A. ;
Ostenfeld, Marie S. .
JOURNAL OF EXTRACELLULAR VESICLES, 2014, 3 (01)
[16]   Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components [J].
Ji, Hong ;
Greening, David W. ;
Barnes, Thomas W. ;
Lim, Justin W. ;
Tauro, Bow J. ;
Rai, Alin ;
Xu, Rong ;
Adda, Christopher ;
Mathivanan, Suresh ;
Zhao, Wei ;
Xue, Yanhong ;
Xu, Tao ;
Zhu, Hong-Jian ;
Simpson, Richard J. .
PROTEOMICS, 2013, 13 (10-11) :1672-1686
[17]   Helical flows and chaotic mixing in curved micro channels [J].
Jiang, F ;
Drese, KS ;
Hardt, S ;
Küpper, M ;
Schönfeld, F .
AICHE JOURNAL, 2004, 50 (09) :2297-2305
[18]   Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma [J].
Kalra, Hina ;
Adda, Christopher G. ;
Liem, Michael ;
Ang, Ching-Seng ;
Mechler, Adam ;
Simpson, Richard J. ;
Hulett, Mark D. ;
Mathivanan, Suresh .
PROTEOMICS, 2013, 13 (22) :3354-3364
[19]   Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes [J].
Kanwar, Shailender Singh ;
Dunlay, Christopher James ;
Simeone, Diane M. ;
Nagrath, Sunitha .
LAB ON A CHIP, 2014, 14 (11) :1891-1900
[20]   Tumor cell-derived exosomes: A message in a bottle [J].
Kharaziha, Pedram ;
Ceder, Sophia ;
Li, Qiao ;
Panaretakis, Theocharis .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2012, 1826 (01) :103-111