Development of techniqes for the oriented immobilization of bio-sensing molecules

• Project/Area Number: 25870310
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nanobioscience; Nanomaterials chemistry
• Research Institution: Osaka University (2015); Nagoya University (2013-2014)
• Principal Investigator: IIJIMA MASUMI 大阪大学, 産業科学研究所, 特任助教 (40390728)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: バイオナノカプセル / バイオセンサー / バイオセンシング / 分子整列化 / ナノバイオ

Outline of Final Research Achievements

A bio-nanocapsule (BNC) of ~30 nm that displays a tandem form of the protein A-derived immunoglobulin G (IgG) Fc-binding Z domains (designated as ZZ-BNC) has been developed for both clustering and oriented immobilization of IgGs on the solid phase of immunosensors. In this study, we applied ZZ-BNC-scaffold for both clustering and oriented immobilization of not only IgGs but also various biosensing molecules (Fc-fused receptors). We then found that ZZ-BNC could significantly enhance the sensitivity, ligand-binding capacity, and affinity of biosensors. Thus, ZZ-BNC is a unique scaffold for various biosensing molecules on biosensor surface, which could improve various biosensing technologies in a clustering and oriented immobilization manner.

Research Products

• [Journal Article] Bio-nanocapsule-based scaffold improves the sensitivity and ligand-binding capacity of mammalian receptors on the sensor chip (2016)
  • Author(s): Iijima, M., Yoshimoto, N., Niimi, T., Maturana, A.D., Kuroda, S.
  • Journal Title: Biotechnology journal Volume: 印刷中 Issue: 6 Pages: 805-813
  • DOI: 10.1002/biot.201500443
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mutational analysis of hepatitis B virus pre-S1 (9-24) fusogenic peptide (2016)
  • Author(s): Liu, Q., Somiya, M., Shimada, N., Sakamoto, W, Yoshimoto, N., Iijima, M., Tatematsu, K., Nakai, T., Okajima, T., Maruyama, A., Kuroda, S.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Scaffold protein Enigma Homolog 1 overcomes the repression of myogenesis activation by Inhibitor of DNA binding 2 (2016)
  • Author(s): Nakatani, M., Ito, J., Koyama, R., Iijima, M., Yoshimoto, N., Niimi, T., Kuroda, S.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 印刷中
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Bio-nanocapsules displaying various immunoglobulins as an active targeting-based drug delivery system (2016)
  • Author(s): Kenji Tatematsu, Masumi Iijima, Nobuo Yoshimoto, Tadashi Nakai, Toshihide Okajima, Shun’ichi Kuroda
  • Journal Title: Acta Biomaterialia Volume: 35 Pages: 238-247
  • DOI: 10.1016/j.actbio.2016.02.010
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cytokine-dependent activation of the JAK-STAT pathway in Saccharomyces cerevisiae (2016)
  • Author(s): Yoshimoto, N., Ikeda, Y., Tatematsu, K., Iijima, M., Nakai, T., Okajima, T., Tanizawa, K., Kuroda, S.
  • Journal Title: Biotechnology and Bioengineering Volume: 印刷中 Issue: 8 Pages: 1796-1804
  • DOI: 10.1002/bit.25948
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mapping the heparin-binding site of the osteoinductive protein NELL1 by site-directed mutagenesis. (2015)
  • Author(s): Takahashi, K., Imai, A., Iijima, M., Yoshimoto, N., Maturana, A. D., Kuroda, S., and Niimi, T.
  • Journal Title: FEBS Letters Volume: 589 Issue: 24PartB Pages: 4026-4032
  • DOI: 10.1016/j.febslet.2015.11.032
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Scaffold protein enigma homolog activates CREB whereas a short splice variant prevents CREB activation in cardiomyocytes (2015)
  • Author(s): Ito J, Iijima M, Yoshimoto N, Niimi T, Kuroda S, Maturana AD
  • Journal Title: Cellular Signaling Volume: 27 Issue: 12 Pages: 2425-2433
  • DOI: 10.1016/j.cellsig.2015.09.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific antitumor growth activity by radiotherapy (2015)
  • Author(s): Liu Q, Jung J, Somiya M, Iijima M, Yoshimoto N, Niimi T, Maturana AD, Shin SH, Jeong SY, Choi EK, Kuroda S
  • Journal Title: International Journal of Nanomedicine Volume: 10 Pages: 4159-4172
  • DOI: 10.2147/ijn.s84295
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intracellular trafficking of bio-nanocapsule-liposome complex: Identification of fusogenic activity in the pre-S1 region of hepatitis B virus surface antigen L protein (2015)
  • Author(s): Somiya M, Sasaki Y, Matsuzaki T, Liu Q, Iijima M, Yoshimoto N, Niimi T, Maturana AD, Kuroda S
  • Journal Title: Journal of Controlled Release Volume: 212 Pages: 10-18
  • DOI: 10.1016/j.jconrel.2015.06.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] One-step scalable preparation method for non-cationic liposomes with high siRNA content (2015)
  • Author(s): Somiya M, Yamaguchi K, Liu Q, Niimi T, Maturana AD, Iijima M, Yoshimoto N, Kuroda S
  • Journal Title: International Journal of Pharmaceutics Volume: 490 Issue: 1-2 Pages: 316-323
  • DOI: 10.1016/j.ijpharm.2015.05.072
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] バイオナノカプセルを用いたセンシング分子整列化技術によるバイオセンシングの高感度化 (2015)
  • Author(s): 飯嶋 益巳、黒田 俊一
  • Journal Title: 生物工学会誌 Volume: 93 Pages: 1-11
  • NAID: 110009931621
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Oligomerization-induced conformational change in the C-terminal region of Nel-like molecule 1 (NELL1) protein is necessary for the efficient mediation of murine MC3T3-E1 cell adhesion and spreading (2014)
  • Author(s): Nakamura, Y., Hasebe, A., Takahashi, K., Iijima, M., Yoshimoto, N., Maturana, A. D., Ting, K., Kuroda, S., and Niimi T.
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 14 Pages: 9781-9794
  • DOI: 10.1074/jbc.m113.507020
  • Peer Reviewed / Open Access
• [Journal Article] High-throughput de novo screening of receptor agonists with an automated single-cell analysis and isolation system. (2014)
  • Author(s): Yoshimoto N, Tatematsu K, Iijima M, Niimi T, Maturana AD, Fujii I, Kondo A, Tanizawa K, Kuroda S
  • Journal Title: Sci Rep. Volume: 4 Issue: 1 Pages: 4242-4242
  • DOI: 10.1038/srep04242
  • Peer Reviewed / Open Access
• [Journal Article] Cell surface-fluorescence immunosorbent assay for real-time detection of hybridomas with efficient antibody secretion at the single-cell level (2013)
  • Author(s): Kida, A.
  • Journal Title: Analytical Chemistry Volume: 85 Issue: 3 Pages: 1753-1759
  • DOI: 10.1021/ac303067k
  • Peer Reviewed
• [Journal Article] An automated system for high-throughput single cell-based breeding (2013)
  • Author(s): Nobuo Yoshimoto, Akiko Kida, Xu Jie, Masaya Kurokawa, Masumi Iijima, Tomoaki Niimi, Andrés D. Maturana, Itoshi Nikaido, Hiroki R. Ueda, Kenji Tatematsu, Katsuyuki Tanizawa, Akihiko Kondo, Ikuo Fujii, Shun'ichi Kuroda
  • Journal Title: Scientific Reports Volume: 3 Issue: 1 Pages: 1191-1191
  • DOI: 10.1038/srep01191
  • Peer Reviewed / Open Access
• [Journal Article] Nanocapsule-based probe for evaluating the orientation of antibodies immobilized on a solid phase (2013)
  • Author(s): Iijima, M., et al. (他 4 名)
  • Journal Title: Analyst Volume: 138 Issue: 12 Pages: 3470-3477
  • DOI: 10.1039/c3an00481c
  • Peer Reviewed
• [Journal Article] A bio-nanocapsule containing envelope protein domain III of Japanese encephalitis virus protects mice against lethal Japanese encephalitis virus infection. (2013)
  • Author(s): Miyata T, Tafuku S, Harakuni T, Tadano M, Yoshimoto N, Iijima M, Matsuo H, Matsuzaki G, Kuroda S, Arakawa T
  • Journal Title: Microbiology and Immunology Volume: 57 Issue: 6 Pages: 470-477
  • DOI: 10.1111/1348-0421.12055
  • Peer Reviewed
• [Journal Article] Bio-Nanocapsules for Signal Enhancement of Alkaline Phosphatase-Linked Immunosorbent Assays (2013)
  • Author(s): Iijima, M., Yamamoto, M., Yoshimoto, N., Niimi, T., Kuroda, S.
  • Journal Title: Bioscience, Biotechnology, and Biochemistry Volume: 77 Issue: 4 Pages: 843-846
  • DOI: 10.1271/bbb.120760
  • NAID: 10031170729
  • ISSN: 0916-8451, 1347-6947
  • Peer Reviewed
• [Journal Article] バイオナノカプセルを用いるイムノセンシング分子整列化技術 (2013)
  • Author(s): 飯嶋 益巳、黒田 俊一
  • Journal Title: バイオサイエンスとインダストリー Volume: 71 Pages: 314-317
  • Peer Reviewed
• [Presentation] Reconstituted ZZ-L particles and planar ZZ-L membrane for the oriented immobilization of Fc-fused molecules on various types of biosensors (2016)
  • Author(s): Iijima, M., Kuroda S.
  • Organizer: Biosensors2016
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 2016-05-25
  • Int'l Joint Research
• [Presentation] High efficiency penetration of antibody-immobilized nanoneedle thorough plasma membrane for in situ detection of cytoskeletal proteins in living cells (2016)
  • Author(s): Shimizu, K., Kawamura, R., Iijima, M., Kuroda, S., Fukazawa, K., Ishihara, K., Nakamura, C.
  • Organizer: Biosensors2016
  • Place of Presentation: Gothenburg, Sweden
  • Year and Date: 2016-05-25
  • Int'l Joint Research
• [Presentation] Detection of vimentin using antibody-modified nanoneedle and AFM to eliminate undifferentiated iPS cells (2015)
  • Author(s): Shimizu, K., Kawamura, R., Kobayashi, T., Iijima, M., Kuroda, S., Iwata, F., Fukazawa, K., Ishihara, K., Nakamura, C
  • Organizer: Pacifichem 2015
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2015-12-15 – 2015-12-20
• [Presentation] Detection of vimentin using antibody-modified nanoneedle and AFM to eliminate undifferentiated iPS cells (2015)
  • Author(s): Shimizu, K., Kawamura, R., Kobayashi, T., Iijima, M., Kuroda, S., Iwata, F., Fukazawa, K., Ishihara, K., Nakamura, C.
  • Organizer: Pacifichem2015
  • Place of Presentation: Honolulu, USA
  • Year and Date: 2015-12-15
  • Int'l Joint Research
• [Presentation] Bio-nanocapsule-based Scaffold for Biosensing Techniques: A Clustering and Oriented Immobilization of Sensing Molecules (2015)
  • Author(s): Iijima, M., Kuroda S.
  • Organizer: The 19th SANKEN International Symposium
  • Place of Presentation: Osaka, Japan
  • Year and Date: 2015-12-07
  • Int'l Joint Research
• [Presentation] バイオナノカプセル足場分子を用いたセンシング分子整列化技術の受容体リガンド検出への応用 (2015)
  • Author(s): 飯嶋益巳、黒田 俊一
  • Organizer: 第67回日本生物工学会大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-10-26
• [Presentation] バイオナノカプセルを用いた抗炎症タンパク質MTI-IIの生体内ピンポイント送達法の開発 (2015)
  • Author(s): 立松健司、岡本一起、飯嶋益巳、黒田 俊一
  • Organizer: 第67回日本生物工学会大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-10-26
• [Presentation] ビメンチンを標的とした未分化ヒトiPS細胞の機械的分離 (2015)
  • Author(s): 清水桂太、川村隆三、小林 健、飯嶋益巳、黒田俊一、岩田 太、中村 史
  • Organizer: 第67回日本生物工学会大会
  • Place of Presentation: 鹿児島
  • Year and Date: 2015-10-26
• [Presentation] Bio-nanocapsule scaffold for oriented immobilization and clustering of sensing molecules on biosensor surfaces (2015)
  • Author(s): Iijima, M., Kuroda S
  • Organizer: 4th International Conference on Bio-Sensing Technology
  • Place of Presentation: Lisbon, Portugal
  • Year and Date: 2015-05-10 – 2015-05-13
• [Presentation] エンド-β-N-アセチルグルコサミニダーゼを用いたB型肝炎ウイルス様粒子の糖鎖構造改変 (2015)
  • Author(s): 岡本雄太・三崎亮・飯嶋益巳・大橋貴生・黒田俊一・藤山和仁
  • Organizer: 日本農芸化学会2015年度大会
  • Place of Presentation: 岡山
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] ネスチンを標的とした神経幹細胞の機械的分離技術の開発 (2015)
  • Author(s): 宮崎みなみ・清水桂太・松本大亮・川村隆三・小林 健・飯嶋益巳・黒田俊一・岩田 太・中村 史
  • Organizer: 電気化学会第82回大会
  • Place of Presentation: 横浜
  • Year and Date: 2015-03-15 – 2015-03-17
• [Presentation] 抗体分子の整列提示能及びクラスタリング能を有するナノキャリア「バイオナノカプセル」を用いた抗体医薬を機能向上させる新ストラテジー (2014)
  • Author(s): 荒木 響子、劉 秋実、曽宮 正晴、飯嶋益巳、黒田俊一
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] バイオナノカプセル足場技術によるバイオセンサー表面のセンシング分子精密整列化およびクラスター化 (2014)
  • Author(s): 飯嶋益巳、黒田俊一
  • Organizer: 第8回バイオ関連化学シンポジウム
  • Place of Presentation: 岡山
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] バイオナノカプセル融合As16抗原による豚における抗体産生誘導 (2014)
  • Author(s): 松本安喜、Nguyen Thi Nga、Nguyen Thanh Lam、三好猛晴、飯嶋益巳、黒田俊一、辻 尚利
  • Organizer: 第157回日本獣医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-09 – 2014-09-12
• [Presentation] 未分化iPS細胞分離に向けた免疫力学検出 (2014)
  • Author(s): 清水桂太、川村隆三、飯嶋益巳、黒田俊一、深澤今日子、石原一彦、中村史
  • Organizer: 第66回日本生物工学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-09 – 2014-09-11
• [Presentation] バイオナノカプセル-リポソーム複合体による抗がん剤（ドキソルビシン）のヒト肝臓由来組織への能動的送達 (2014)
  • Author(s): 劉 秋実、仲本拓央、曽宮正晴、飯嶋益巳、黒田俊一
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-30 – 2014-07-31
• [Presentation] バイオナノカプセルを用いた無線QCMの高感度化 (2014)
  • Author(s): 野井健太郎、飯嶋益巳、黒田俊一、荻博次、平尾雅彦
  • Organizer: 第14回日本蛋白質科学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-25 – 2014-06-27
• [Presentation] Bio-nanocapsule scaffold for oriented immobilization and clustering of sensing molecules on biosensor surfaces (2014)
  • Author(s): Iijima, M., Kuroda, S.
  • Organizer: Biosensors2014
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2014-05-27 – 2014-05-31
• [Presentation] Mechanical cell sorting using antibody-immobilized nanoneedle array (2014)
  • Author(s): Miyazaki, M., Kawamura, R., Rao, S.R., Kobayashi, T., Iijima, M., Kuroda, S., Iwata, F., Nakamura, C.
  • Organizer: Biosensors2014
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2014-05-27 – 2014-05-31
• [Presentation] Enhancement of mass-detection sensitivity in wireless-electrodeless QCM biosensors by bio-nanocapsules (2014)
  • Author(s): Noi, K., Ogi, H., Iijima, M., Kuroda, S., Hirao, M.
  • Organizer: Biosensors2014
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2014-05-27 – 2014-05-31
• [Presentation] バイオナノカプセルを用いたセンシング分子整列化技術の開発 (2014)
  • Author(s): 飯嶋益巳、黒田俊一
  • Organizer: 名古屋大学 予防早期医療創成センター 第4回ワークショップ
  • Place of Presentation: 名古屋
• [Presentation] ナノニードルアレイを用いた細胞分離における細胞アレイの接着力制御 (2014)
  • Author(s): 宮崎みなみ、川村隆三、サトゥルリラマチャンドラ ラオ、小林 健、飯嶋益巳、黒田俊一、岩田 太、中村 史
  • Organizer: 日本化学会第94春季年会(2014)
  • Place of Presentation: 名古屋
• [Presentation] Enhancement of mass-detection sensitivity in wireless-electrodeless QCM biosensors by bio-nanocapsules. (2014)
  • Author(s): Noi, K., Ogi, H., Iijima, M., Kuroda, S., Hirao, M.
  • Organizer: Biosensors2014
  • Place of Presentation: Melbourne, Australia
• [Presentation] Bio-nanocapsule scaffold for oriented immobilization and clustering of sensing molecules on biosensor surfaces. (2014)
  • Author(s): Iijima, M., Kuroda S.
  • Organizer: Biosensors2014
  • Place of Presentation: Melbourne, Australia
• [Presentation] Bio-nanocapsules for optimizing nanostructure of biosensor surface. (2013)
  • Author(s): Iijima, M., Kuroda, S.
  • Organizer: 3rd International Conference on Bio-Sensing Technology
  • Place of Presentation: Sitges, Spain
• [Presentation] In vivo active delivery of antigens with dendritic cell-targeting Bio-nanocapsules (2013)
  • Author(s): Matsuo, H., Tomioka, M., Yoshimoto, N., Iijima, M., Kuroda S.
  • Organizer: Vaccine Delivery and Stabilization: Improving the Reach of Vaccines
  • Place of Presentation: Boston, USA
• [Presentation] 抗体修飾ナノニードルを用いた細胞の機械的分離 (2013)
  • Author(s): 宮崎みなみ、清水桂太、川村隆三、サトゥルリラマチャンドラ ラオ、小林 健、飯嶋益巳、黒田俊一、深澤今日子、石原一彦、岩田 太、中村 史
  • Organizer: 第65回日本生物工学会大会
  • Place of Presentation: 広島
• [Presentation] バイオナノカプセル技術による豚回虫感染防御抗原As16の抗体産生増強効果 (2013)
  • Author(s): 松本安喜、Nguyen Thi Nga、Nguyen Thanh Lam、三好猛晴、飯嶋益巳、黒田俊一、辻 尚利
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜
• [Presentation] 抗体修飾ナノニードルによる細胞の釣り上げ分離 (2013)
  • Author(s): 宮崎みなみ、川村隆三、サトゥルリラマチャンドラ ラオ、小林 健、飯嶋益巳、黒田俊一、深澤今日子、石原一彦、岩田 太、中村 史
  • Organizer: 第7回バイオ関連化学シンポジウム
  • Place of Presentation: 名古屋
• [Presentation] 細胞の機械的分離に向けたナノニードルの抗体修飾と細胞培養基板の接着制御 (2013)
  • Author(s): 川村隆三、宮崎みなみ、サトゥルリラマチャンドラ ラオ、小林 健、飯嶋益巳、黒田俊一、深澤今日子、石原一彦、岩田 太、中村 史
  • Organizer: 第7回バイオ関連化学シンポジウム
  • Place of Presentation: 名古屋
• [Presentation] バイオセンサー表面でセンシング分子を精密整列化するバイオナノカプセル (2013)
  • Author(s): 飯嶋益巳、黒田俊一
  • Organizer: 第7回バイオ関連化学シンポジウム
  • Place of Presentation: 名古屋
• [Presentation] センシング分子ナノレベル整列化技術を用いた高機能バイオセンサーの開発 (2013)
  • Author(s): 飯嶋 益巳
  • Organizer: BioJapan2013 World Business Fourum、2013年度バイオインダストリー協会賞、発酵と代謝研究奨励賞、生物素材研究開発奨励賞合同発表会
  • Place of Presentation: 横浜
  • Invited
• [Book] DDSキャリア作製プロトコル集 (2015)
  • Author(s): 飯嶋益巳、黒田俊一
  • Total Pages: 262
  • Publisher: CMC出版
• [Remarks] 生体分子ナノレベル整列固定化技術の開発
  • URL: http://www.sanken.osaka-u.ac.jp/labs/smb/Biosensor.html
• [Remarks] １０倍超す高感度、低コスト効率よく…臨床検査法を実用化 阪大、免疫測定法に抗体「足場」分子
  • URL: http://www.sankei.com/west/news/160105/wst1601050051-n1.html
• [Remarks] BNCのバイオセンサー、イムノアッセイへの応用研究
  • URL: http://www.agr.nagoya-u.ac.jp/~tagen/tagen/home.html
• [Remarks] BNCのバイオセンサー、イムノアッセイへの応用研究
  • URL: http://www.agr.nagoya-u.ac.jp/~tagen/tagen/home.html.html
• [Patent(Industrial Property Rights)] センシング基板及びそれを用いたリガンドの測定方法 (2014)
  • Inventor(s): 黒田俊一、飯嶋益巳
  • Industrial Property Rights Holder: 黒田俊一、飯嶋益巳
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-064090
  • Filing Date: 2014-03-26