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Sci Adv. 2017 Dec 15;3(12):e1701133. doi: 10.1126/sciadv.1701133. eCollection 2017 Dec.

Unveiling massive numbers of cancer-related urinary-microRNA candidates via nanowires.

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Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
ImPACT Research Center for Advanced Nanobiodevices, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Japan Science and Technology Agency, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Institute of Materials Chemistry and Engineering, Kyushu University, 6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580, Japan.
Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka-cho, Ibaraki, Osaka 567-0047, Japan.
College of Nanotechnology, King Mongkut's Institute of Technology Ladkrabang, Chalongkrung Road, Ladkrabang, Bangkok 10520, Thailand.
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Health Research Institute, National Institute of Advanced Industrial Science and Technology, Takamatsu 761-0395, Japan.
College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.


Analyzing microRNAs (miRNAs) within urine extracellular vesicles (EVs) is important for realizing miRNA-based, simple, and noninvasive early disease diagnoses and timely medical checkups. However, the inherent difficulty in collecting dilute concentrations of EVs (<0.01 volume %) from urine has hindered the development of these diagnoses and medical checkups. We propose a device composed of nanowires anchored into a microfluidic substrate. This device enables EV collections at high efficiency and in situ extractions of various miRNAs of different sequences (around 1000 types) that significantly exceed the number of species being extracted by the conventional ultracentrifugation method. The mechanical stability of nanowires anchored into substrates during buffer flow and the electrostatic collection of EVs onto the nanowires are the two key mechanisms that ensure the success of the proposed device. In addition, we use our methodology to identify urinary miRNAs that could potentially serve as biomarkers for cancer not only for urologic malignancies (bladder and prostate) but also for nonurologic ones (lung, pancreas, and liver). The present device concept will provide a foundation for work toward the long-term goal of urine-based early diagnoses and medical checkups for cancer.

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