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Sci Rep. 2017 Apr 24;7:46224. doi: 10.1038/srep46224.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer.

Liang LG1,2,3, Kong MQ1,2,3, Zhou S4, Sheng YF1,2,3, Wang P5, Yu T1,2,3, Inci F4, Kuo WP6,7, Li LJ1,2, Demirci U4,8, Wang S1,2,3,4.

Author information

1
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
2
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang Province, 310003, China.
3
Institute for Translational Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310029, China.
4
Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University, School of Medicine, Palo Alto, CA 94304 USA.
5
Department of Urology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
6
Harvard Catalyst-Laboratory for Innovative Translational Technologies, Harvard Medical School, Boston, MA 02115, USA.
7
CloudHealth Genomics, Ltd, Shanghai, 201499, China.
8
Department of Electrical Engineering (By courtesy), Stanford University, Stanford, CA 94305, USA.

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30-200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings.

PMID:
28436447
PMCID:
PMC5402302
DOI:
10.1038/srep46224
[Indexed for MEDLINE]
Free PMC Article

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