Molecular profiling of extracellular vesicles via charge-based capture using oxide nanowire microfluidics


Posted: 2021-09-20 19:00:00
Biosens Bioelectron . 2021 Aug 27;194:113589. doi: 10.1016/j.bios.2021.113589. Online ahead of print. Takao Yasui 1 , Piyawan Paisrisarn 2 , Takeshi Yanagida 3 , Yuki Konakade 2 , Yuta Nakamura 2 , Kazuki Nagashima 4 , Marina Musa 2 , Ivan Adiyasa Thiodorus 2 , Hiromi Takahashi 2 , Tsuyoshi Naganawa 2 , Taisuke Shimada 2 , Noritada Kaji 5 , Takahiro Ochiya 6 , Tomoji Kawai 7 , Yoshinobu Baba 8 Affiliations Expand Affiliations 1 Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan; Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan. Electronic address: yasui@chembio.nagoya-u.ac.jp. 2 Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan. 3 Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan; The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka-cho, Ibaraki, Osaka, 567-0047, Japan; Institute for Materials Chemistry and Engineering, Kyushu University, 6-1 Kasuga-Koen, Kasuga, Fukuoka, 816-8580, Japan. Electronic address: yanagida@g.ecc.u-tokyo.ac.jp. 4 Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan; Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. 5 Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Moto-oka 744, Nishi-ku, Fukuoka, 819-0395, Japan. 6 Department of Molecular and Cellular Medicine, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjuku-ku, Tokyo, 160-0023, Japan. 7 The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka-cho, Ibaraki, Osaka, 567-0047, Japan. 8 Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Anagawa 4-9-1, Inage-ku, Chiba, 263-8555, Japan. Electronic address: babaymtt@chembio.nagoya-u.ac.jp. Item in Clipboard Takao Yasui et al. Biosens Bioelectron. 2021. Show details Display options Display options Format Biosens Bioelectron . 2021 Aug 27;194:113589. doi: 10.1016/j.bios.2021.113589. Online ahead of print. Authors Takao Yasui 1 , Piyawan Paisrisarn 2 , Takeshi Yanagida 3 , Yuki Konakade 2 , Yuta Nakamura 2 , Kazuki Nagashima 4 , Marina Musa 2 , Ivan Adiyasa Thiodorus 2 , Hiromi Takahashi 2 , Tsuyoshi Naganawa 2 , Taisuke Shimada 2 , Noritada Kaji 5 , Takahiro Ochiya 6 , Tomoji Kawai 7 , Yoshinobu Baba 8 Affiliations 1 Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan; Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan. Electronic address: yasui@chembio.nagoya-u.ac.jp. 2 Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan. 3 Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan; The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka-cho, Ibaraki, Osaka, 567-0047, Japan; Institute for Materials Chemistry and Engineering, Kyushu University, 6-1 Kasuga-Koen, Kasuga, Fukuoka, 816-8580, Japan. Electronic address: yanagida@g.ecc.u-tokyo.ac.jp. 4 Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan; Department of Applied Chemistry, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. 5 Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Department of Chemistry and Biochemistry, Graduate School of Engineering, Kyushu University, Moto-oka 744, Nishi-ku, Fukuoka, 819-0395, Japan. 6 Department of Molecular and Cellular Medicine, Tokyo Medical University, 6-7-1 Nishishinjyuku, Shinjuku-ku, Tokyo, 160-0023, Japan. 7 The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka-cho, Ibaraki, Osaka, 567-0047, Japan. 8 Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan; Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology, Anagawa 4-9-1, Inage-ku, Chiba, 263-8555, Japan. Electronic address: babaymtt@chembio.nagoya-u.ac.jp. Item in Clipboard CiteDisplay options Display options Format Abstract Extracellular vesicles (EVs) have shown promising features as biomarkers for early cancer diagnoses. The outer layer of cancer cell-derived EVs consists of organotropic metastasis-induced membrane proteins and specifically enriched proteoglycans, and these molecular compositions determine EV surface charge. Although many efforts have been devoted to investigating the correlation between EV subsets obtained through density-, size-, and immunoaffinity-based captures and expressed membrane proteins, understanding the correlation between EV subsets obtained through surface charge-based capture and expressed membrane proteins is lacking. Here, we propose a methodology to profile membrane proteins of EV subsets obtained through surface charge-based capture. Nanowire-induced charge-based capture of EVs and in-situ profiling of EV membrane proteins are the two key methodology points. The oxide nanowires allowed EVs to be obtained through surface charge-based capture due to the diverse isoelectric points of the oxides and the large surface-to-volume ratios of the nanowire structures. And, with the ZnO nanowire device, whose use does not require any purification and concentration processes, we demonstrated the correlation between negatively-charged EV subsets and expressed membrane proteins derived from each cell. Furthermore, we determined that a colon cancer related membrane protein was overexpressed on negatively charged surface EVs derived from colon cancer cells. Keywords: Extracellular vesicle; Extracellular vesicle membrane protein; In-situ profiling of extracellular vesicle membrane protein; Microfluidics; Nanowire; Nanowire-induced charge-based capture. Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved. 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