2022/01/21 更新

写真a

オノ ツトム
小野 努
ONO Tsutomu
所属
自然科学学域 教授
職名
教授
外部リンク

学位

  • 博士(工学) ( 九州大学 )

研究キーワード

  • マイクロ流体工学

  • マイクロカプセル

  • ナノ繊維

  • ソフトマター

  • 拡散分離工学

研究分野

  • ものづくり技術(機械・電気電子・化学工学) / 移動現象、単位操作

  • ものづくり技術(機械・電気電子・化学工学) / バイオ機能応用、バイオプロセス工学

  • ものづくり技術(機械・電気電子・化学工学) / 反応工学、プロセスシステム工学

学歴

  • 九州大学    

    1994年4月 - 1998年5月

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    国名: 日本国

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  • 九州大学   Faculty of Engineering  

    1990年4月 - 1994年3月

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    国名: 日本国

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経歴

  • 岡山大学   自然科学研究科   教授

    2012年4月 - 現在

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  • 岡山大学   環境学研究科   准教授

    2006年4月 - 2012年3月

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  • スタンフォード大学   客員研究員

    2004年3月 - 2005年3月

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    国名:アメリカ合衆国

    備考:文部科学省在外研究員

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  • 九州大学   工学研究科   助教

    1998年8月 - 2006年3月

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  • 日本学術振興会特別研究員

    1997年4月 - 1998年8月

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所属学協会

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委員歴

  • 公益社団法人化学工学会   庶務理事  

    2020年4月 - 現在   

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    団体区分:学協会

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  • 一般社団法人日本繊維機械学会   理事  

    2020年4月 - 現在   

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    団体区分:学協会

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  • 公益社団法人化学工学会 材料・界面部会 ソフトマター工学分科会   副代表  

    2020年4月 - 2022年3月   

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  • 公益社団法人化学工学会 反応工学部会 マイクロ化学プロセス分科会   代表  

    2020年3月 - 現在   

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    団体区分:学協会

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  • 公益社団法人化学工学会 材料・界面部会 ソフトマター工学分科会   代表  

    2016年3月 - 2020年3月   

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    団体区分:学協会

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  • 公益社団法人化学工学会 社会実装学研究会   幹事  

    2016年 - 現在   

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    団体区分:学協会

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  • 公益社団法人化学工学会 材料・界面部会   幹事  

    2016年 - 現在   

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    団体区分:学協会

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  • 公益社団法人化学工学会   理事  

    2015年4月 - 2017年4月   

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    団体区分:学協会

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論文

  • One-pot synthesis of poly(ionic liquid)s with 1,2,3-triazolium-based backbones via clickable ionic liquid monomers

    Ruka Hirai, Tatsuki Hibino, Takaichi Watanabe, Takashi Teranishi, Tsutomu Ono

    10   37743 - 37748   2020年10月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Induction of foaming in vacuum drying by needle stimulation and the impact of solution viscosity, vapor pressure, and the type of solute and solvent 査読

    Akiho Fujioka, Rina Yamamoto, Olivier Tramis, Hiroaki Ishida, Tsutomu Ono, Naoyuki Ishida, Koreyoshi Imamura

    Drying Technology   1 - 13   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/07373937.2021.2017965

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  • Multilayer Poly(ionic liquid) Microcapsules Prepared by Sequential Phase Separation and Subsequent Photopolymerization in Ternary Emulsion Droplets 査読

    Takaichi Watanabe, Yuka Yasuhara, Tsutomu Ono

    ACS Applied Polymer Materials   2021年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acsapm.1c01315

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  • Preparation of Monodisperse Poly(Methyl Methacrylate)/Polystyrene Composite Particles by Seeded Emulsion Polymerization Using a Sequential Flow Process 査読

    Takaichi Watanabe, Kengo Karita, Midori Manabe, Tsutomu Ono

    Frontiers in Chemical Engineering   3   63   2021年11月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3389/fceng.2021.742447

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  • Design of Clickable Ionic Liquid Monomers to Enhance Ionic Conductivity for Main-Chain 1,2,3-Triazolium-Based Poly(Ionic Liquid)s 査読

    Ruka Hirai, Takaichi Watanabe, Tsutomu Ono

    ACS Omega   6 ( 15 )   10030 - 10038   2021年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acsomega.0c06173

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  • One-pot synthesis of poly(ionic liquid)s with 1,2,3-triazolium-based backbonesviaclickable ionic liquid monomers 査読

    Ruka Hirai, Tatsuki Hibino, Takaichi Watanabe, Takashi Teranishi, Tsutomu Ono

    RSC Advances   10 ( 62 )   37743 - 37748   2020年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/d0ra07948k

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  • Flow synthesis of monodisperse micron-sized polymer particles by heterogeneous polymerization using a water-in-oil slug flow with a non-ionic surfactant 査読

    Takaichi Watanabe, Kengo Karita, Tsutomu Ono

    Colloid and Polymer Science   298 ( 9 )   1273 - 1281   2020年9月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00396-020-04705-5

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  • Flow synthesis of monodisperse micron-sized polymer particles by heterogeneous polymerization using water-in-oil slug flow with non-ionic surfactant 査読

    Takaichi Watanabe, Kengo Karita, Tsutomu Ono

    Colloid Polym. Sci.   298   1273 - 1281   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Preparation of tough, thermally stable, and water-resistant double-network ion gels consisting of silica nanoparticles/poly(ionic liquid)s through photopolymerisation of an ionic monomer and subsequent solvent removal 査読

    Takaichi Watanabe, Ruri Takahashi, Tsutomu Ono

    Soft Matter   16 ( 6 )   1572 - 1581   2020年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1039/c9sm02213a

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  • Metal Microcapsules Prepared via Electroless Plating at Liquid–Liquid Interface 査読

    Toshihiko Tsuneyoshi, Yunlong Cui, Hiroaki Ishida, Takaichi Watanabe, Tsutomu Ono

    Langmuir   35 ( 41 )   13311 - 13317   2019年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.langmuir.9b00181

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  • Rapid Synthesis of Poly(methyl methacrylate) Particles with High Molecular Weight by Soap‐Free Emulsion Polymerization Using Water‐in‐Oil Slug Flow 査読

    Takaichi Watanabe, Kengo Karita, Koki Tawara, Takuya Soga, Tsutomu Ono

    Macromolecular Chemistry and Physics   220 ( 9 )   1900021 - 1900021   2019年5月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/macp.201900021

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/macp.201900021

  • Microfluidic Formation of Hydrogel Microcapsules with a Single Aqueous Core by Spontaneous Cross-Linking in Aqueous Two-Phase System Droplets 査読

    Takaichi Watanabe, Ibuki Motohiro, Tsutomu Ono

    Langmuir   35 ( 6 )   2358 - 2367   2019年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.langmuir.8b04169

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  • Free-Standing Metal Films Prepared via Electroless Plating at Liquid–Liquid Interfaces 査読

    Toshihiko Tsuneyoshi, Yu Yohaze, Takaichi Watanabe, Tsutomu Ono

    Langmuir   34 ( 44 )   13183 - 13191   2018年11月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acs.langmuir.8b02822

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  • Polydopamine-Based 3D Colloidal Photonic Materials: Structural Color Balls and Fibers from Melanin-Like Particles with Polydopamine Shell Layers 査読

    Michinari Kohri, Kenshi Yanagimoto, Ayaka Kawamura, Kosuke Hamada, Yoshihiko Imai, Takaichi Watanabe, Tsutomu Ono, Tatsuo Taniguchi, Keiki Kishikawa

    ACS Applied Materials & Interfaces   10 ( 9 )   7640 - 7648   2018年3月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1021/acsami.7b03453

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  • Metal-coated microcapsules with tunable magnetic properties synthesized via electroless plating 査読

    Toshihiko Tsuneyoshi, Tsutomu Ono

    MATERIALS SCIENCE AND ENGINEERING B-ADVANCED FUNCTIONAL SOLID-STATE MATERIALS   222   49 - 54   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Metal-coated microcapsules with tunable magnetic properties, which contained liquid cores and metallic Ni-P alloy shells, were synthesized via electroless plating. The fabrication process consisted of emulsification, phase separation, and electroless Ni plating stages. The material composition and sizes of Ni single crystals in the obtained metallic shells depended on the pH of the plating solution. It was found that the microcapsules prepared at high pH values (8.0 and 10.0) were characterized by ferromagnetic properties, whereas those synthesized at low pH values (4.7 and 6.0) were superparamagnetic. The produced micro capsules have potential applications as magnetic responsive carriers of phase change materials, which can be easily transferred to a desired place by applying external magnetic field. (c) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.mseb.2017.04.009

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  • Indocyanine green-laden poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules incorporating reverse micelles: Effects of PEG-b-PLA composition on the nanocapsule diameter and encapsulation efficiency 査読

    Takaichi Watanabe, Yui Sakamoto, Tetsuya Inooka, Yukitaka Kimura, Tsutomu Ono

    COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS   520   764 - 770   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Reverse micelles are thermodynamically stable systems, with a capacity to encapsulate hydrophilic molecules in their nanosized core, which is smaller than the core generally obtained with water in -oil-emulsion droplets. Herein, we present a simple technique for the preparation of poly(ethylene glycol)-block-polylactide (PEG-b-PLA) nanocapsules encapsulating a hydrophilic photosensitizer (indocyanine green, ICG), which exploits reverse micelle formation and subsequent emulsion-solvent diffusion. We establish the effect of the PEG-b-PLA composition and the co-surfactant volume on the diameter and water content of the reverse micelles. We demonstrate that the composition of PEG-b-PIA affects also the diameter and encapsulation efficiency of the resulting nanocapsules. We show that the ICG-laden nanocapsulescon fabricated under the most optimal conditions have a diameter of approximately 100 nm and an ICG encapsulation efficiency of 58%. We believe that the method proposed here is a promising step towards the preparation of hydrophilic drug-laden polymer nanocapsules with a small diameter and therefore suitable for use in drug delivery applications based on enhanced permeability and retention (EPR) effect-driven passive targeting. (C) 2017 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.colsurfa.2017.02.039

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  • Synthesis and characterization of a polyoxometalate-based ionic liquid catalyst for delignification of wood biomass 査読

    Kemal Volkan Ozdokur, Muhammad Moniruzzaman, Jale Yanik, Tsutomu Ono

    WOOD SCIENCE AND TECHNOLOGY   50 ( 6 )   1213 - 1226   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Conversion of recalcitrant lignocellulosic biomass to renewable and valuable biopolymers has attracted global interest to build up sustainable societies. Delignification of biomass for separating such biopolymers (e.g., cellulose and lignin) has been used as an efficient process. However, conventional delignification methods suffer from considerable drawbacks and cannot be considered as clean processes. In this study, a new type of polyoxometalate (POM) ionic liquid (IL), [(C6N2H11)(42)][Mo132O372 (CH3COO)(30)(H2O)(72)].ca 284 H2O ([1-ethyl-3-methylimidazolium] [Mo132O372 (CH3COO)(30) (H2O)(72)].ca 184 H2O) (abbreviated as [emim]POM), was synthesized and employed as a catalyst in the delignification of wood biomass. The synthesized [emim]POM catalyst was characterized by CNH analysis, Fourier transform infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The results indicated that the 1-ethyl-3-methylimidazolium [emim] group was appended to a (NH4)(42) [Mo132O372(CH3COO)(30) (H2O)(72)].ca 120 H2O POM precursor in which the [emim] group replaced the ammonium group. The [emim]POM catalyst effectively delignified wood in an IL [emim][OAc] (1-ethyl-3-methylimidazolium acetate) system: The lignin content of the produced cellulose-rich material was ca. 7.0 %, much lower than the 32.0 % lignin content of the untreated wood biomass. The delignification efficiency was improved by optimizing IL catalyst loading, the IL concentration, and the reaction conditions. This POM-based IL could be used in the delignification of lignocellulosic biomass to isolate cellulose and lignin for further chemical and mechanical processing.

    DOI: 10.1007/s00226-016-0844-y

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  • Efficient anti-tumor effect of photodynamic treatment with polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer encapsulating hydrophobic porphyrin derivative 査読

    Ken-ichi Ogawara, Taro Shiraishi, Tomoya Araki, Taka-ichi Watanabe, Tsutomu Ono, Kazutaka Higaki

    European Journal of Pharmaceutical Sciences   82   154 - 160   2015年11月

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  • Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature 査読

    Tomoya Araki, Ken-ichi Ogawara, Haruka Suzuki, Rie Kawai, Taka-ichi Watanabe, Tsutomu Ono, Kazutaka Higaki

    JOURNAL OF CONTROLLED RELEASE   200   106 - 114   2015年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The effects of photo-triggered tumor vascular treatment (PVT) on the structural and functional properties of tumor vasculature were assessed in Colon-26 (C26) and B16/BL6 (B16) tumor-bearing mice. Furthermore, anti-tumor efficacy of subsequently injected PEG liposomal paclitaxel (PL-PTX) was also evaluated. As a photosensitizer, a hydrophobic porphyrin derivative was used and formulated in polymeric nanoparticle composed of polyethylene glycol-block-polylactic acid to avoid its non-specific in vivo disposition. In the mice bearing C26 with high permeable vasculature, the prominent anti-tumor activity was confirmed by PVT alone, but the subsequently injected PL-PTX did not show any additive effect. PVT itself initially induced apoptotic cell death of tumor vascular endothelial cells and platelet aggregation, which would have subsequently induced apoptosis of C26 tumor cells surrounding the vasculature. On the other hand, in the mice bearing B16 with low permeable vasculature, PVT enhanced the anti-tumor activity of subsequently injected PL-PTX, which would be attributed to the tumor disposition amount and area of PEG liposomes enhanced by PVT. These results clearly indicated that the treatment would have made it possible to provide more efficient extravasation of PL-PTX, leading to its more potent anti-tumor effect. (C) 2015 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.jconrel.2014.12.038

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  • Preparation of biodegradable foam from walnut shells treated by subcritical water 査読

    Wei Yang, Ichiro Shimizu, Tsutomu Ono, Yukitaka Kimura

    Journal of Chemical Technology and Biotechnology   90 ( 1 )   44 - 49   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:John Wiley and Sons Ltd  

    BACKGROUND: Subcritical water treatment is considered an environment-friendly method to liquefy biomass to prepare valuable chemicals. Several researchers have studied the solid obtained after autohydrolysis treatment for use as reinforcement in biocomposities and was the base pulp and paper technologies. The novelty of this present research is the use of solid in the manufacture of starch foams. RESULTS: Subcritical water was used to extract hemicellulosic carbohydrate from walnut shells at temperatures from 160 to 260°C for 15min and at 200°C for various treatment times. The maximum yield was obtained at 200°C for 15min. The residue of the walnut shells obtained at the maximum carbohydrates extraction yield was used to prepare a biodegradable foam by compounding with corn starch using a technique similar to compression molding. It was found that replacing 20% of the corn starch by the residue had no deleterious effects on the density and morphology, as indicated by scanning electron microscopy. The prepared foams had a dense outer skin and a less dense interior with large, mostly open cells. The flexural strains were similar to that of foamed polystyrene and the flexural modulus and flexural stresses were larger. CONCLUSION: It was considered that the prepared biodegradable foam was a promising material to take the place of plastic products in the future.

    DOI: 10.1002/jctb.4451

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  • Microfluidic Approach to the Formation of Internally Porous Polymer Particles by Solvent Extraction 査読

    Takaichi Watanabe, Carlos G. Lopez, Jack F. Douglas, Tsutomu Ono, Joao T. Cabral

    LANGMUIR   30 ( 9 )   2470 - 2479   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    We report the controlled formation of internally porous polyelectrolyte particles with diameters ranging from tens to hundreds of micrometers through selective solvent extraction using microfluidics. Solvent-resistant microdevices, fabricated by frontal photopolymerization, encapsulate binary polymer (P)/solvent (Si) mixtures by a carrier solvent phase (C) to form plugs with well-defined radii and low polydispersity; the suspension is then brought into contact with a selective extraction solvent (S2) that is miscible with C and Si but not P, leading to the extraction of Si from the droplets. The ensuing phase inversion yields polymer capsules with a smooth surface but highly porous internal structure. Depending on the liquid extraction time scale, this stage can be carried out in situ, within the chip, or ex situ, in an external S2 bath. Bimodal polymer plugs are achieved using asymmetrically inverted T junctions. For this demonstration, we form sodium poly(styrenesulfonate) (P) particles using water (S1), hexadecane (C), and methyl ethyl ketone (S2). We measure droplet extraction rates as a function of drop size and polymer concentration and propose a simple scaling model to guide particle formation. We find that the extraction time required to form particles from liquid droplets does not depend on the initial polymer concentration but is rather proportional to the initial droplet size. The resulting particle size follows a linear relationship with the initial droplet size for all polymer concentrations, allowing for the precise control of particle size. The internal particle porous structure exhibits a polymer density gradient ranging from a dense surface skin toward an essentially hollow core. Average particle porosities between 10 and 50% are achieved by varying the initial droplet compositions up to IS wt % polymer. Such particles have potential applications in functional, optical, and coating materials.

    DOI: 10.1021/la404506b

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  • Laccase Incorporated into PEG-PLA Polymer as Active and Stable Biocatalyst for Ionic Liquids Media 査読

    Muhammad Moniruzzaman, Yoichiro Nao, Sekhar Bhattacharjee, Tsutomu Ono

    PROCESS AND ADVANCED MATERIALS ENGINEERING   625   333 - +   2014年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:TRANS TECH PUBLICATIONS LTD  

    Laccase Y20 (EC. 1.10.3.2) was coated with poly (ethylene glycol)-block-polylactide (PEG-PLA, M-W = 27680) via water-in-oil emulsion, and the activity and stability of the resulting PEG-PLA-laccase complex have been compared to those for the native laccase and lyophilized native laccase in an ionic liquid (IL) [C(2)mim][PF6] (1-ethyl-3-methylimidazolium hexafluorophosphate. The formation of spherical PEG-PLA-laccase complex of 330-480 nm was demonstrated by scanning electron microscopy. This polymer-laccase complex retained most of its enzymatic catalytic activity and exhibited excellent storage stability in IL, with over 70% of its initial activity retained after 12 days of storage in IL at 40 degrees C, whereas it was about 20% for native laccase under the identical conditions. This strategy could be employed to fabricate polymer based composites materials with novel biological functions.

    DOI: 10.4028/www.scientific.net/AMM.625.333

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  • Monodisperse polylactide microcapsules with a single aqueous core prepared via spontaneous emulsification and solvent diffusion 査読

    Takaichi Watanabe, Yukitaka Kimura, Tsutomu Ono

    RSC ADVANCES   4 ( 10 )   4872 - 4877   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    A simple approach to preparing monodisperse poly(D, L-lactide) (PDLLA) microcapsules with a single aqueous core is developed. The method is based on automatic water-in-oil-in-water double emulsion formation from oil-in-water single emulsion via spontaneous emulsification which voluntarily disperses part of continuous aqueous phase into the dispersed oil phase dissolving oil-soluble amphiphilic diblock copolymer, poly(D, L-lactide)-b-poly(2-dimethylaminoethyl methacylate)(PDLLA-b-PDMAEMA), followed by coalescence of tiny water droplets within the polymer droplets, coupled with quick precipitation of polymers by diluting the emulsion with water. In this study, we have investigated the effect of PDLLA to PDLLA-b-PDMAEMA ratios and flow rates of each solution during preparing the emulsion on the final morphology and the size of the microcapsules. It was found that the polymer blend ratio played a crucial role in determining internal structure of the microcapsules. The microcapsules size decreased with the increment of the flow rate ratios of the continuous phase to the dispersed phase and eventually reached 10 mm, while maintaining narrow size distribution. In addition, we have demonstrated that the microcapsules can encapsulate both hydrophilic and hydrophobic compounds during the formation.

    DOI: 10.1039/c3ra44066d

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  • Microfluidic Fabrication of Monodisperse Polylactide Microcapsules with Tunable Structures through Rapid Precipitation 査読

    Takaichi Watanabe, Yukitaka Kimura, Tsutomu Ono

    LANGMUIR   29 ( 46 )   14082 - 14088   2013年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    We describe a versatile and facile route to the continuous production of monodisperse polylactide (PLA) microcapsules with controllable structures. With the combination of microfluidic emulsification, solvent diffusion, and internal phase separation, uniform PLA microcapsules with a perfluorooctyl bromide (PFOB) core were successfully obtained by simply diluting monodisperse ethyl acetate (EA)-in-water emulsion with pure water. Rapid extraction of EA from the droplets into the aqueous phase enabled the solidification of the polymer droplets in a nonequilibrium state during internal phase separation between a concentrated PLA/EA phase and a PFOB phase. Higher-molecular-weight PLA generated structural complexity of the microcapsules, yielding core-shell microcapsules with covered with small PFOB droplets. Removal of the PFOB via freeze drying gave hollow microcapsules with dimpled surfaces. The core-shell ratios and the diameter of these microcapsules could be finely tuned by just adjusting the concentration of PFOB and flow rates on emulsification, respectively. These biocompatible microcapsules with controllable size and structures are potentially applicable in biomedical fields such as drug delivery carriers of many functional molecules.

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  • Coupling Microreaction Technologies, Polymer Chemistry, and Processing to Produce Polymeric Micro and Nanoparticles with Controlled Size, Morphology, and Composition 査読

    Christophe A. Serra, Bruno Cortese, Ikram Ullah Khan, Nicolas Anton, Mart H. J. M. de Croon, Volker Hessel, Tsutomu Ono, Thierry Vandamme

    MACROMOLECULAR REACTION ENGINEERING   7 ( 9 )   414 - 439   2013年9月

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    記述言語:英語   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Polymeric micro- and nanoparticles receive the attention of researchers in different areas such as drug delivery, sensing, imaging, cosmetics, diagnostics, and biotechnology. However, processes with conventional equipment do not always allow precise control of their morphology, size, size distribution, and composition. On the other hand, microreaction technology offers improved control over the hydrodynamics, mass and heat transfer, allowing production of polymeric particles with better defined or new characteristics. Thus new horizons in polymer particle engineering arise from the use of microstructured or microfluidic devices. This article gives an insight into the latest developments and trends in the production of polymeric micro- and nanoparticles realized by microreaction technology directly.

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  • Separation and characterization of cellulose fibers from cypress wood treated with ionic liquid prior to laccase treatment 査読

    Muhammad Moniruzzaman, Tsutomu Ono

    BIORESOURCE TECHNOLOGY   127   132 - 137   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Separation of cellulose fibers (CFs) from woody biomass with minimal structural alteration using a "green" and efficient method was achieved by treatment with the ionic liquid (IL), [emim][OAc] (1-ethyl-3-methylimidazolium acetate) at 80 degrees C for 1 h. The IL was recovered by rinsing with water-acetone mixture prior to treatment of the wood with Trametes sp. laccase in the presence of 1-hydroxybenzotriazole as a mediator. IL pretreatment did not significantly change the chemical composition of the wood, but did alter its structure and rendered its surface more accessible to the enzyme. Treated and untreated samples were characterized by SEM, FTIR, XRD, TGA, and chemical methods. The cellulose content of the produced fibers was approximately 73.1% and the lignin content was 9.8%, much lower than the lignin content of 29.3% of the untreated wood. The cellulose fibers exhibited higher cellulose crystallinity and better thermal stability compared to untreated wood materials. (C) 2012 Elsevier Ltd. All rights reserved.

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  • Simplified model for extraction of 5-hydroxymethylfurfural from fructose: Use of water/oil biphasic system under high temperature and pressure conditions 査読

    Toshinori Shimanouchi, Yoshitaka Kataoka, Masahiro Yasukawa, Tsutomu Ono, Yukitaka Kimura

    Solvent Extraction Research and Development   20   205 - 212   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japan Association of Solvent Extraction  

    5-Hydroxymethylfurfural (HMF) was obtained from the dehydration of fructose under high temperature and pressure conditions (180 °C and 10 MPa). To avoid the decomposition of HMF in the bulk aqueous phase, we dehydrated fructose in the water / metyl isobuthyl ketone (MIBK) biphasic system. The HMF could be successfully extracted into the organic MIBK phase without further decomposition of HMF. We present a simplified model taking into consideration of the slug flow with the wall film to maximize the HMF yield in the MIBK phase. It was likely that the slug flow contributed to an increase in the surface-to-volume ratio for the mass transfer of HMF.

    DOI: 10.15261/serdj.20.205

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  • Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer 査読

    Tomoya Araki, Yusuke Kono, Ken-ichi Ogawara, Takaichi Watanabe, Tsutomu Ono, Toshikiro Kimura, Kazutaka Higaki

    BIOLOGICAL & PHARMACEUTICAL BULLETIN   35 ( 8 )   1306 - 1313   2012年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PHARMACEUTICAL SOC JAPAN  

    To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG) and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical properties of PN-PTX prepared were assessed; the mean particle size was around 80nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX release property was assessed by a dialysis method. Although rapid release of PTX was observed just after dosing, around 70% of PTX was stably incorporated in polymeric nanoparticles for a long time in the presence of serum. Then, the in vivo pharmacokinetics of PN-PTX after intravenous administration was investigated in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX incorporated exhibited a long blood circulating property, leading to enhanced permeability and retention (EPR) effect-driven, time-dependent tumor disposition of PTX. Tumor distribution increased gradually for 24h, and tissue uptake clearance of polymeric nanoparticles in the liver and spleen was lower than that of PEG liposomes. Since these results indicated that the in vivo disposition characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any significant anti-tumor effect, presumably due to the poor PTX release from polymeric nanoparticles. From these results, it is considered that the favorable pharmacokinetic properties of nanoparticles and the drug incorporated do not always lead to its potent in vivo pharmacological activity, suggesting the importance of PTX release properties within tumor tissues.

    DOI: 10.1248/bpb.b12-0020

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  • Ionic liquid assisted enzymatic delignification of wood biomass: A new 'green' and efficient approach for isolating of cellulose fibers 査読

    Muhammad Moniruzzaman, Tsutomu Ono

    BIOCHEMICAL ENGINEERING JOURNAL   60   156 - 160   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The objective of this study was to provide a new environmentally friendly and efficient approach for isolating cellulose fibers with minimum structural alteration from wood biomass. The method comprised enzymatic delignification of ionic liquid (IL) swollen wood biomass in ILs-aqueous systems with the aim of overcoming low delignification efficiency associated with the difficulties in enzyme accessibility to the solid substrate and the poor substrate and products solubility in aqueous system. It was found that the cellulose rich wood fibers obtained from biological pretreatment in IL-aqueous systems contained significantly lower amounts of lignin as compared to those found in conventional methods. The treated wood fibers were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and X-ray diffractometry (XRD) and compared those with untreated wood fibers. (C) 2011 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bej.2011.11.001

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  • Design and Evaluation of Emulsion Generation Device Using Ultrasonic Vibration and Microchannel 査読

    Takefumi Kanda, Takuya Harada, Yoshiyuki Tominaga, Koichi Suzumori, Tsutomu Ono, Sotaro Iwabuchi, Kazuyuki Ito, Ken-ichi Ogawara, Kazutaka Higaki, Yuta Yoshizawa

    JAPANESE JOURNAL OF APPLIED PHYSICS   50 ( 7 )   2011年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IOP PUBLISHING LTD  

    The aim of this research is to realize a small continuous flow system with emulsification devices. This system is designed for the generation of sub-micron or nano monodisperse emulsions. In this study, we have designed, fabricated, and evaluated a device that consists of a microchannel plate and an ultrasonic vibrating plate. This device can realize a continuous flow system and the plates are easily stacked. The oscillation frequency was 2.25 MHz. We succeeded in generating emulsions that have a diameter of 200 nm. We also designed the cross-sectional pattern of the microchannel of the ultrasonic device to increase residence time effectively. As a result, we have succeeded in obtaining emulsions that have a diameter of 80 nm. (C) 2011 The Japan Society of Applied Physics

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  • Microfluidic Extraction of Docosahexaenoic Acid Ethyl Ester: Comparison between Slug Flow and Emulsion 査読

    Eiji Kamio, Yu Seike, Hidekazu Yoshizawa, Hideto Matsuyama, Tsutomu Ono

    INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH   50 ( 11 )   6915 - 6924   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Microfluidic liquid-liquid extraction of the ethyl ester of docosahexaenoic acid (DHA-Et) with silver ions was investigated using slug flow and a water-in-oil (W/O) emulsion as specific flow patterns possessing large interfacial areas. To compare the extraction rates of both systems, slug flow and a W/O emulsion with similar specific interfacial areas were prepared. Extraction rates for the systems were the same at 298 K However, at 268 K, slug flow had a faster extraction rate than the W/O emulsion. Theoretical calculation follows the results for both systems at 298 K and for the slug flow system at 268 K, suggesting that the emulsion stabilizer inhibits complex formation between DHA-Et and silver ions at the O/W interface. A reduction in extraction rate was observed in the slug flow system at 268 K when the emulsion stabilizer was used. Slug flow can be prepared without stabilizer, offering advantages over emulsions in microfluidic extraction.

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  • Release Behavior from Hydrogen-Bonded Polymer Gels Prepared by Pressurization 査読

    Shingo Mutsuo, Kazuya Yamamoto, Tsutomu Furuzono, Tsuyoshi Kimura, Tsutomu Ono, Akio Kishida

    JOURNAL OF APPLIED POLYMER SCIENCE   119 ( 5 )   2725 - 2729   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Our previous research showed that a simple ultra-high-pressure process made poly(vinyl alcohol) (PVA) solution into a macrogel and nanoparticles. To investigate the release properties of PVA hydrogels prepared by the ultra-high-pressure treatment, we prepared hydrogels containing model drugs by pressurizing a PVA solution with Alfa-G Hesperidin or Oil Blue N as a water-soluble or an oil-soluble model drug, respectively. In the case of the oil-soluble drug, an oil-in-water emulsion, Oil Blue N containing dodecane in a PVA solution, was used by homogenization before pressurization. The average diameter and the diameter distribution of oil droplets before and after the ultra-high-pressure treatment were almost the same. However, the PVA hydrogel prepared at 10,000 atm for 10 min exhibited the slowest release rate of model drugs. Thus, we found that the release rates of the model drugs from the PVA hydrogels were controlled by the degree of crosslinking in the resulting gels, which was determined from the operation parameters of the ultrahigh-pressure treatment, such as the pressure, time, and concentration of the PVA solution. Therefore, an ultrahigh-pressure process is promising for drug-carrier development because of the nonharmful simple preparation process. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 2725-2729, 2011

    DOI: 10.1002/app.31622

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  • Monodisperse Water-in-Water-in-Oil Emulsion Droplets 査読 国際誌

    Masahiro Yasukawa, Eiji Kamio, Tsutomu Ono

    CHEMPHYSCHEM   12 ( 2 )   263 - 266   2011年2月

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    記述言語:英語   出版者・発行元:WILEY-V C H VERLAG GMBH  

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  • Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion-solvent diffusion 査読

    Takaichi Watanabe, Tsutomu Ono, Yukitaka Kimura

    SOFT MATTER   7 ( 21 )   9894 - 9897   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    Monodisperse polylactide (PLA) microspheres were continuously fabricated by microfluidic emulsification and subsequent dilution in water. The diameter was precisely tuned from 6 to 50 mu m by changing the flow rate of the fluids in microfluidics or the PLA concentration in the dispersed phase. The use of amphiphilic oil-soluble poly(ethylene glycol)-b-polylactide (o-PEG-PLA) as a matrix resulted in a highly porous microsphere morphology, and the porosity was controlled by blending PLA. Therefore, mono-disperse PLA microspheres with the predetermined surface porosity were continuously produced by just enough reagents and energy.

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  • Modeling of extraction behavior of docosahexaenoic acid ethyl ester by utilizing slug flow prepared by microreactor 査読

    Eiji Kamio, Yu Seike, Hidekazu Yoshizawa, Tsutomu Ono

    AIChE Journal   56 ( 8 )   2163 - 2172   2010年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The liquid-liquid extraction dynamics of an ethyl ester of docosahexaenoic acid (DHA-Et) with silver ion was investigated. The kinetic model was derived according to the following stepwise processes: Diffusion of DHA-Et across the organic film, complex-formation between DHA-Et and silver ion at the interface, and diffusion of extracted complex across the aqueous film. The kinetic parameters for the complex-formation reaction were determined from the investigation with the stirred transfer cell. With the proposed model and determined parameters, we predicted the uptakes of DHA-Et for the extraction system utilizing a slug flow prepared by a microchip. The calculated uptakes showed good correlation to the experimental data. The theoretical investigation suggested that the fast equilibration realized for the slug flow extraction system was due to the large specific interfacial area of the slug caused by the presence of wall film and the thin liquid film caused by the internal circulation. © 2009 American Institute of Chemical Engineers.

    DOI: 10.1002/aic.12132

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  • PEG-PLA nanoparticles prepared by emulsion solvent diffusion using oil-soluble and water-soluble PEG-PLA 査読

    Makoto Muranaka, Ken Hirota, Tsutomu Ono

    MATERIALS LETTERS   64 ( 8 )   969 - 971   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Poly(ethylene glycol)-block-polylactide (PEG-PLA) nanoparticles were prepared through the oil-in-water (O/W, ethyl acetate/water) emulsion technique using oil-soluble PEG-PLA in the presence of water-soluble PEG-PLA as a surfactant. The particle diameter decreased with increasing water-soluble PEG-PLA concentration, the smallest averaged diameter was 75 nm. From these results, it was found that water-soluble PEG-PLA acted as a surfactant which prevents further coalescence of droplets. In addition, the particles diameter decreased with increasing hydrophile-lipophile balance of oil-soluble PEG-PLA in the absence of water-soluble PEG-PLA. In contrast, the particle diameter was constant in the presence of water-soluble PEG-PLA. Therefore, the capability of water-soluble PEG-PLA as a surfactant was more excellent than that of oil-soluble PEG-PLA. (C) 2010 Elsevier B.V. All rights reserved

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  • A Versatile Biodegradable Polymer with a Thermo-Reversible/Irreversible Transition 査読

    Fumiaki Tanimoto, Yoshiro Kitamura, Tsutomu Ono, Hidekazu Yoshizawa

    ACS APPLIED MATERIALS & INTERFACES   2 ( 3 )   606 - 610   2010年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    A versatile biodegradable thermoresponsive polymer was developed. The polymer has succinimide and isopropylasparamide segments and exhibits a phase transition with thermoreversibility that can be controlled by changing the polymer composition. With fewer succinimide units, the polymer exhibits the type of thermo-reversible phase transition that is characteristic of poly(N-isopropylacrylamide) (PNIPAAm). The polymer with a higher proportion of succinimide units exhibits a thermo-irreversible phase transition, resulting in the formation of nanospheres that are stable below the transition temperature. The stable nanospheres are generated by dehydration and subsequent conformational stabilization through an interaction between imide rings. This thermoirreversible phase transition in water provides a simple, oil-free preparation of biodegradable nanospheres.

    DOI: 10.1021/am900705s

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  • An emulsion generating microchannel device oscillated by piezoelectric vibrator 査読

    Takefumi Kanda, Koichi Suzumori, Takuya Harada, Tsutomu Ono, Sotaro Iwabuchi, Kazuyuki Ito, Ken-Ichi Ogawara, Kazutaka Higaki

    2010 International Symposium on Micro-NanoMechatronics and Human Science: From Micro and Nano Scale Systems to Robotics and Mechatronics Systems, MHS 2010, Micro-Nano GCOE 2010, Bio-Manipulation 2010   13 - 18   2010年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

    The goal of this study is to realize an emulsification device for the generation of sub-micron size monodisperse emulsions. We have fabricated and tested the device which consists of a microchannel plate and an ultrasonic vibrating plate. The device can realize continuous flow system and those plates are easily stacked. We have succeeded in generating emulsions which has a diameter of 80 nm. ©2010 IEEE.

    DOI: 10.1109/MHS.2010.5669586

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  • Emulsion Generating Microchannel Device Oscillated by 2.25MHz Ultrasonic Vibrator 査読

    Takuya Harada, Takefumi Kanda, Koichi Suzumori, Tsutomu Ono, Sotaro Iwabuchi, Kazuyuki Ito, Ken-ichi Ogawara, Kazutaka Higaki

    JAPANESE JOURNAL OF APPLIED PHYSICS   49 ( 7 )   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:IOP PUBLISHING LTD  

    In this study, a device using an ultrasonic vibration and a microchannel has been developed to obtain emulsions. The process of generating emulsions involves a Y-type microchannel and an ultrasonic device. Once micron-sized emulsions were generated by the Y-type microchannel, the micron-sized emulsions were sonicated using ultrasonic vibration to produce emulsions. Although the diameter of emulsions was 30 mu m using the Y-type microchannel, the diameter of the sonicated emulsions was about 200 nm. In addition, as the applied voltage was increased, sonicated emulsions became smaller and the distribution became sharper. (C) 2010 The Japan Society of Applied Physics

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  • Role of Dispersion Stabilizer with Hydroxy Groups in Preparation of Monodisperse Polylactide Microspheres 査読

    Makoto Muranaka, Tsutomu Ono

    JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY   47 ( 20 )   5230 - 5240   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Monodisperse poly(D,L-lactide) (PDLLA) microspheres were prepared by dispersion polymerization of D,L-lactide in xylene/heptane (1/2, v/v) with poly[(dodecyl methacrylate)-co-(2-hydroxyethyl methacrylate)] (P(DMA-co-HEMA)) as a dispersion stabilizer. P(DMA-co-HEMA) contains hydroxy groups, which act as an initiation group for pseudoanionic dispersion polymerization. The best coefficient of variation (CV) values concerning particle diameter distribution and the particle diameter of obtained PDLLA microspheres were 3.7% and 5.3 mu m, respectively. The particle diameter decreased with increasing concentration of P(DMA-co-HEMA) and HEMA maintained low CV (<10%) values. As a result, monodisperse PDLLA microspheres ranging from 1.3 to 5.3 mu m were obtained. In addition, it was found that monodisperse PDLLA microspheres were obtained by sufficient capture of growing polymers and monomers in the particle growth stage. Therefore, the HEMA concentration in P(DMA-co-HEMA) strongly affecting the capturing capability is the most important factor. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5230-5240, 2009

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  • Heterogeneous Polymerization with Polyaspartate Macromonomer Having Vinyl Pendant Groups. II. Control of Particle Diameter and Diameter Distribution in Dispersion Copolymerization 査読

    Keisuke Tomita, Tsutomu Ono

    JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY   47 ( 9 )   2281 - 2288   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    To control particle diameter and particle diameter distribution in dispersion copolymerization of styrene and sodium polyaspartate macromonomer containing vinylbenzyl pendant groups, effects of some polymerization parameters, water contents, initiator concentration, styrene monomer concentration, reaction temperature, and type of initiator on the particle diameter and the diameter distribution were investigated. Variation of the water contents from 20 to 80 vol % controls the resultant particle diameter from 0.066 to 0.47 pm. The diameter increased with increasing initiator concentration. This tendency is similar to dispersion polymerization system using a nonpolymerizable stabilizer. Particle diameter distribution broadened with increasing styrene monomer concentration. This trend was attributed to the increase of a period of particle formation. This result indicated that the period of particle formation affected the resultant particle diameter distribution. Particle diameter distribution was successfully improved (CV = 9.1 from 23.6%) by shortening of decomposition time of initiator. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2281-2288, 2009

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  • Design of polylactide-grafted copolymeric stabilizer for dispersion polymerization of D,L-lactide 査読

    Makoto Muranaka, Hidekazu Yoshizawa, Tsutomu Ono

    COLLOID AND POLYMER SCIENCE   287 ( 5 )   525 - 532   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Poly(D,L-lactide) (PDLLA) microspheres with narrow diameter distribution were prepared by dispersion polymerization of D,L-lactide in xylene/heptane (1:2, v/v) using poly(dodecyl methacrylate)-g-poly(D,L-lactide) (PDMA-g-PDLLA) as a dispersion stabilizer. The particle diameters of PDLLA microspheres were controlled from 200 nm to 5 mu m by altering the concentration and the graft chain number of PDMA-g-PDLLA. The effect of the copolymer composition on the particle diameter was investigated to clarify an important factor of the copolymer structure for the control of the particle diameter. As a result, it was necessary for anchor block in diblock copolymer as a dispersion stabilizer to have low solubility in the solution rather than the compatibility with particles. Moreover, we confirmed by dynamic light scattering measurement that PDMA-g-PDLLA formed micelles in the solution. In conclusion, it was clarified that PDLLA microspheres with a wide range of particle diameter were prepared due to the different kinetic stability of micelles.

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  • Heterogeneous Polymeriozation with Polyaspartate Macromonomer Having Vinyl Pendant Groups. I. Synthesis of Macromonomer and Dispersion Copolymerization of Styrene 査読

    Keisuke Tomita, Tsutomu Ono

    JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY   47 ( 3 )   762 - 770   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Sodium polyaspartate (PAspNa) derivatives with vinylbenzyl pendant groups (VBA-PAspNa) were synthesized by reaction of poly(succinimide) (PSI) and vinylbenzylamine (VBA), and hydrolysis by sodium hydroxide (NaOH) solution. VBA-PAspNa is a macromonomer with multiple vinyl groups in the side chain. Submicron sized polymeric particles were prepared by dispersion copolymerization of styrene with VBA-PAspNa in a mixture of ethanol and water. Particle diameter decreased with increasing concentration and vinyl group fraction of VBA-PAspNa. When compared with the particle diameter prepared using PAspNa or benzylamine-modified PAspNa (BA-PAspNa) as a dispersion stabilizer without vinyl groups, the particles prepared with VBA-PAspNa were an order smaller than those prepared with PAspNa or BA-PAspNa. The particles after refinement show an adequate negative zeta-potential. From this result, we clarified the presence of PAspNa chains anchored onto the particle surface. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 762-770, 2009

    DOI: 10.1002/pola.23192

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  • Preparation of Monodisperse Polylactide Microspheres by Dispersion Polymerization Using a Polymeric Stabilizer with Hydroxy Groups 査読

    Makoto Muranaka, Tsutomu Ono

    MACROMOLECULAR RAPID COMMUNICATIONS   30 ( 3 )   152 - 156   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-V C H VERLAG GMBH  

    Monodisperse poly(D,L-lactide) (PDLLA) microspheres have been prepared by dispersion polymerization Of D,L-lactide with a synthetic polymeric stabilizer. The polymerization is carried out in xylene/heptane (1:2, v/v) at 368 K for 3 h with poly[(dodecyl methacrylate)-co-(2-hydroxyethyl methacrylate)] (P(DAAA-co-HEMA)). P(DMA-co-HEMA) has hydroxy groups as an initiation group for pseudoanionic dispersion polymerization. The particle diameter and the coefficient of variation concerning the diameter distribution of the obtained PDLLA microspheres are 3.9 mu m and 4.3%, respectively. In addition, from the results of dynamic light scattering measurements, it is found that P(DMA-co-HEMA) and the PDLLA-grafted copolymer form a micellar structure in solution.

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  • Synthesis of polyaspartate macromonomer having a vinyl end group and application to dispersion copolymerization of styrene 査読

    Keisuke Tomita, Tsutomu Ono

    COLLOID AND POLYMER SCIENCE   287 ( 1 )   109 - 113   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Sodium polyaspartate (PAspNa) macromonomer with an acryloyl end group was synthesized for dispersion polymerization. At first, a poly(succinimide) (PSI) derivative with a hydroxyphthalimide end group was synthesized by polycondensation of l-aspartic acid and 4-hydroxyphthalic acid. Then, the PSI derivative was end-capped with an acryloyl group by a reaction with acrlyloyl chloride. Finally, a PAspNa derivative with a vinyl end group was synthesized by a hydrolysis of succinimide units by sodium hydroxide. The synthesized macromonomer was applied as a polymerizable stabilizer in dispersion copolymerization of styrene in a mixture of ethanol and water. The PAspNa macromonomer acted as an effective stabilizer and gave sub-micron-sized polymeric particles in dispersion polymerization in polar medium.

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  • Design of a new static micromixer having simple structure and excellent mixing performance 査読

    Eiji Kamio, Tsutomu Ono, Hidekazu Yoshizawa

    LAB ON A CHIP   9 ( 12 )   1809 - 1812   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ROYAL SOC CHEMISTRY  

    A novel micromixer with simple construction and excellent mixing performance is developed. The micromixer is composed of two stainless steel tubes with different diameters: one is an outer tube and another is an inner tube which fits in the outer tube. In this micromixer, one reactant fluid flows in the mixing zone from the inner tube and the other flows from the outer tube. The excellent mixing performance is confirmed by comparing the results of a Villermaux/Dushman reaction with those for the other micromixers. The developed micromixer has a mixing cascade with multiple means and an asymmetric structure to achieve effective mixing. The excellent mixing performance of the developed micromixer suggests that serial addition of multiple phenomena for mixing will give us an efficient micromixing.

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  • Microcapsules with Macroholes Prepared by the Competitive Adsorption of Surfactants on Emulsion Droplet Surfaces 査読

    Eiji Kamio, Satoshi Yonemura, Tsutomu Ono, Hidekazu Yoshizawa

    LANGMUIR   24 ( 23 )   13287 - 13298   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    We demonstrate a simple, unique method for preparing microcapsules with holes in their shells. Cross-linked polymelamine microcapsules are prepared by the phase-separation method. The holey shell of each microcapsule is synthesized on the surface of an oil-in-water (O/W) emulsion droplet where a water-soluble polymeric surfactant and an oil-soluble surfactant are competitively adsorbed. The water-soluble polymeric surfactant provides a reaction site for shell formation. The oil-soluble surfactant molecules seem to self-assemble while the shells are being formed, so holes appear where they assemble. The critical degree of surface coverage of an emulsion droplet by the water-soluble polymeric surfactant needed to form the holey shells is determined to be 0.90 from theoretical calculations in which competitive adsorption is considered. Theoretical consideration suggests that the size and quantity of the holes in the microcapsule shells are controlled by the composition of the surfactants adsorbed on the surface of an emulsion droplet. This theoretical consideration is confirmed by experiments. The prepared microcapsule with controllable macroholes in its shell has the potential to be used for controlled release applications and can be used to fabricate a microcapsule that encapsulates hydrophilic compounds.

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  • Effects of dispersion stabilizer and reaction solvent on forming monodisperse polystyrene microspheres by dispersion polymerization 査読

    Takuro Nakashima, Tsutomu Ono

    COLLOID AND POLYMER SCIENCE   286 ( 14-15 )   1587 - 1592   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    We used poly(aspartic acid) (PAsp) synthesized by ion exchange with sodium polyaspartate (PAspNa) as a dispersion stabilizer. PAsp improved the dispersion stability and the solubility in the medium for dispersion polymerization. The effects of the stabilizer hydrophobicity on particle formation, conversion, particle diameter, and its distribution of polystyrene microspheres were investigated by using both biodegradable polymers as a dispersion stabilizer. According to these results, we concluded that the polymerization rate of the styrene with PAsp was higher than that of styrene with PAspNa. That is why, smaller and more monodisperse microspheres were prepared with PAsp, compared to those with PAspNa.

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  • Preparation of monodisperse crosslinked polymelamine microcapsules by phase separation method 査読

    Eiji Kamio, Aiko Kato, Satoshi Yonemura, Tsutomu Ono, Hidekazu Yoshizawa

    Colloid and Polymer Science   286 ( 6-7 )   787 - 793   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Monodisperse polymelamine microcapsules were prepared by phase separation method. Control of microcapsule diameter was investigated using the uniform-sized oil-in-water emulsion droplets as the capsule core. The monodisperse emulsion droplets were prepared using the Shirasu porous glass (SPG) membrane emulsification technique. The effects of the diameter of the oil droplet and concentration of sodium dodecyl sulfate (SDS), which is a typical emulsifier in SPG membrane emulsification, on microencapsulation were investigated. The microcapsules were aggregated when oil droplets with small size were microencapsulated at high SDS concentration. To reduce the SDS concentration, the creamed emulsion was used. The monodisperse polymelamine microcapsules were successfully prepared by using the creamed emulsion. The microcapsule diameter was almost similar to the diameter of the encapsulated oil droplet. The coefficient of variation values was about 10% for all microcapsules prepared in this study. Control of microcapsule diameter was achieved in the range of 5-60 μm. © Springer-Verlag 2008.

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  • Pressure-induced molecular assembly of hydrogen-bonded polymers 査読

    Tsutomu Ono, Shingo Mutsuo, Kazuya Yamamoto, Tsutomu Furuzono, Tsuyoshi Kimura, Akio Kishida

    Journal of Polymer Science, Part B: Polymer Physics   46 ( 7 )   743 - 750   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Controlling the noncovalent bondings such as electrostatic interaction, van der Waals force and hydrogen bond, is the key factor to generate molecular assembly. We show that pressure is one of the most intensive variables for controlling these intermolecular forces and producing assembled structure. Macrogel and nanoparticles of hydrogen-bonded polymers were simply obtained through an ultrahigh-pressure process. The morphology of the obtained assembly depends on concentration and various conditions of the pressurization. These results indicate that the ultrahigh-pressure induces inter/intra-hydrogen bond, which is strong enough to maintain microassemblies such as gels and particles. This methodology leads to the molecular design of pressure-induced molecular assembly, and nonharmful processes for molecular separation and drug development. © 2008 Wiley Periodicals, Inc.

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  • 架橋メラミンマイクロカプセル膜形成に及ぼす界面活性剤の電荷の影響

    米村 慧, 神尾 英治, 小野 努

    化学工学会 研究発表講演要旨集   2008   613 - 613   2008年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2008.0.613.0

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  • Extraction of ethyl ester of polyunsaturated fatty acids by utilizing slug flow prepared by microreactor 査読

    Yu Seike, Eiji Kamio, Tsutomu Ono, Hidekazu Yoshizawa

    Journal of Chemical Engineering of Japan   40 ( 12 )   1076 - 1084   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    By utilizing a microreactor, extraction of ethyl ester of docosahexaenoic acid (DHA-Et) and eicosapentaenoic acid (EPA-Et) from an organic solution into an aqueous silver nitrate solution has been investigated. Slug flow preapared by using a T-shape microreactor was used to extract DHA-Et and EPA-Et. Utilizing slug flow created large specific interfacial area between aqueous and organic phases, and ultra fast extraction has been achieved. Extraction of both DHA-Et and EPA-Et took less than 20 s to reach equilibrium. In all of the experiments, the amount of DHA-Et or EPA-Et extracted was the same to that expected from the batch experiment. These facts indicate that the microreactor system can realize an ultra-fast examination system of extraction equilibrium. In addition, by maintaining the temperature quite low, a drastic improvement of extraction ratio is exhibited under a low silver nitrate concentration condition. That is, it can easily cut down silver nitrate by utilizing a microreactor. This is preferable for the practical operation. Copyright © 2007 The Society of Chemical Engineers, Japan.

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  • Digoxin transport by renal proximal tubule cells is enhanced by adhesive synthetic RGD peptide 査読

    Hiroyuki Ijima, S. Kuroda, T. Ono, K. Kawakami

    International Journal of Artificial Organs   30 ( 1 )   25 - 33   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wichtig Editore s.r.l.  

    Introduction: The dialyzer apparatus has been widely used as an artificial kidney in medical treatment. However, side effects such as amyloidosis have occurred during long-term treatment. Therefore, we focused on developing a hybrid artificial kidney with a filtration and reabsorption apparatus, but it was found that cells spread extensively and it is difficult to maintain a uniform monolayer with a regular cell shape on a collagen-coated substrate. The purpose of this study was to improve cell adhesion, uniform stable monolayer formation and active transport function by immobilization of arginine-glycine-aspartic acid (RGD) on the culture substratum. Materials and Methods: Polycarbonate semipermeable membranes were coated with collagen, fibronectin, laminin and synthetic polypeptide, including RGD (Pronectin F). Cell adhesion and digoxin transport were estimated using a renal proximal tubule cell line that overexpressed the P-glycoprotein gene. Results and Discussion: Under initial and confluent conditions, immobilized cell density in Pronectin F-coated wells was higher than that under other conditions. Transepithelial electrical resistance and digoxin transport activity on Pronectin F-coated membranes were the highest of all conditions. This might have been caused by uniform cell morphology and high cell density. © Wichtig Editore, 2007.

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  • 界面吸着平衡に着目した架橋メラミンマイクロカプセル膜形成機構に関する定量的検討

    米村 慧, 神尾 英治, 小野 努, 吉澤 秀和

    化学工学会 研究発表講演要旨集   2007   41 - 41   2007年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2007.0.41.0

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  • 超微細加工技術を利用した金属基盤マイクロミキサーの開発

    神尾 英治, 小野 努, 吉澤 秀和

    化学工学会 研究発表講演要旨集   2007   672 - 672   2007年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2007.0.672.0

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  • マイクロリアクターを用いた硝酸銀水溶液によるDHA-Etの抽出

    清家 雄, 神尾 英治, 小野 努, 吉澤 秀和

    化学工学会 研究発表講演要旨集   2007   827 - 827   2007年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2007.0.827.0

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  • Fabrication of endothelialized tube in collagen gel as starting point for self-developing capillary-like network to construct three-dimensional organs in vitro 査読

    Takayuki Takei, Shinji Sakai, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    BIOTECHNOLOGY AND BIOENGINEERING   95 ( 1 )   1 - 7   2006年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JOHN WILEY & SONS INC  

    A possible strategy for creating three-dimensional (3D) tissue-engineered organs in vitro with similar volumes to the primary organs is to develop a capillary network throughout the constructs to provide sufficient oxygenation and nutrition to the cells composing them. Here, we propose a novel approach for the creation of a capillary-like network in vitro, based on the spontaneous tube-forming activity of vascular endothelial cells (ECs) in collagen gel. We fabricated a linear tube of 500 mu m in diameter,the inner surface of which was filled with bovine carotid artery vascular endothelial cells (BECs), in type I collagen gel as a starting point for the formation of a capillary-like network. The BECs exposed to a medium containing vascular endothelial growth factor (VEGF) migrated into the ambient gel around the tube. After 2 weeks of VEGF exposure, the distance of the migration into the ambient gel in the radial direction of the tube reached approximately 800 pm. Cross-sections of capillary-like structures composed of the migrating BECs, with a lumen-like interior space, were observed in slices of the gel around the tube stained with hematoxylin-eosin (H&E). These results demonstrate that this approach using a pre-established tube, which is composed of ECs, as a starting point for a self-developing capillary-like network is potentially useful for constructing 3D organs in vitro. (c) 2006 Wiley Periodicals, Inc.

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  • Effect of diglucosamine on the entrapment of protein into liposomes 査読

    S Murakami, T Ono, S Sakai, H Ijima, K Kawakami

    JOURNAL OF LIPOSOME RESEARCH   16 ( 2 )   103 - 112   2006年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    Liposomes, which had entrapped bovine serum albumin (BSA), were modified with diglucosamine by two methods. The liposome was prepared by a freeze-thawing method in the presence of the disaccharide, or the disaccharide was added to the liposome prepared in advance without it. To examine the effects of diglucosamine, the morphology, mean particle size, and zeta potential of both liposomes were compared with those of BSA-entrapping liposome prepared without the disaccharide. Diglucosamine caused no remarkable change in shape and no aggregation of the liposome. The presence of the disaccharide was confirmed on the surfaces of modified liposomes, and the entrapment of BSA into the liposomes was increased by the disaccharide. The entrapment behavior was affected by the way the disaccharide was added, and the difference in the way the BSA was entrapped was also indicated.

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  • ホスファチジルグリセロール含有リポソームへのタンパク質の保持特性に及ぼす脂質組成の影響

    村上 直, 藤田 哲也, 小野 努, 境 慎司, 井嶋 博之, 川上 幸衛

    化学工学論文集   32 ( 6 )   514 - 517   2006年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Liposomes composed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) were prepared to examine the effects of lipid composition on surface properties of the liposomes and entrapment efficiency of proteins into the liposomes. Lipid composition was found to influence the amount and mode of proteins entrapped into the PC/PG liposomes, as well as the surface properties of the liposomes. Both electrostatic and non-electrostatic interactions between protein and liposome played important roles in the entrapment of protein into the PC-containing liposomes, and the amount of proteins adsorbed electrostatically on the PG-containing liposomes was also influenced by lipid composition. Copyright © 2006 The Society of Chemical Engineers, Japan.

    DOI: 10.1252/kakoronbunshu.32.514

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  • 遺伝子包括ベシクルの細胞導入効率に関する検討

    藤田 哲也, 小野 努, 境 慎司, 井嶋 博之, 川上 幸衛

    化学工学会 研究発表講演要旨集   2006   994 - 994   2006年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2006f.0.994.0

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  • Enhanced angiogenesis in bFGF-containing scaffold promoted viability of enclosed hepatocytes and maintained hepatospecific glycogen storage capacity

    T Takei, H Ijima, S Sakai, T Ono, K Kawakami

    JOURNAL OF CHEMICAL ENGINEERING OF JAPAN   38 ( 11 )   913 - 917   2005年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC CHEMICAL ENG JAPAN  

    We fabricated a scaffold of poly (lactic acid) and acidic gelatin, a sustained-release carrier of basic fibroblast growth factor (bFGF), which is a positive regulator of angiogenesis. After 1 week of implantation into mesentery of rats, blood vessels induced in the bFGF-containing scaffolds were almost double those in the bFGF-free scaffolds. Further, histological examination of hepatocyte-immobilizing scaffolds retrieved after 1 week of implantation into the mesentery of the rats that received a 70% hepatectomy revealed that the bFGF-containing scaffolds were more efficient for immobilized cell survival than the bFGF-free scaffolds. As well, hepatocytes in the bFGF-containing scaffolds kept their hepatospecific glycogen storage capacity.

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  • Development of mammalian cell-enclosing subsieve-size agarose capsules (&lt;100 μm) for cell therapy 査読

    Shinji Sakai, Kenji Kawabata, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Biomaterials   26 ( 23 )   4786 - 4792   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Agarose capsules were prepared using a droplet breakup method in a coflowing stream. Subsieve-size capsules 76±9 μm in diameter were obtained by extruding 4 wt% agarose solution from a needle (300 μm inner diameter) at a velocity of 1.2 cm/s into an ambient liquid paraffin flow of 20.8 cm/s. Increasing the flow rate of the liquid paraffin and decreasing that of the agarose solution resulted in a decreased resultant capsule diameter. Reduction in diameter from several hundred micrometers to subsieve-size (&lt
    100 μm) enhanced molecular exchange and mechanical stability. Measurements based on the percentage of intact mitochondria in the cells demonstrated that the viability of the enclosed cells was independent of capsule diameter. No significant difference was observed between the viabilities of cells enclosed in capsules with diameters of 79±8 and 351±41 μm (p=0.43). Compared with cells seeded in a tissue culture dish, the cells enclosed in the subsieve-size capsules showed 89.2% viability. © 2004 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.biomaterials.2004.11.043

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  • Enhancement of liver-specific functions of primary rat hepatocytes co-cultured with bone marrow cells on tissue culture-treated polystyrene surfaces 査読

    Hiroyuki Ijima, Sunao Murakami, Takeshi Matsuo, Takayuki Takei, Tsutomu Ono, Koei Kawakami

    Journal of Artificial Organs   8 ( 2 )   104 - 109   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Primary rat hepatocytes were co-cultured with bone marrow cells (BMCs) in a tissue culture-treated culture well (TCW) or a collagen-coated culture well (CCW). Although a medium containing serum was used, the co-cultured cells formed spheroids on the TCW within 2 days, and ammonia metabolism and albumin secretion activities were well maintained for 3 weeks. The co-cultured cells formed a monolayer on the CCW within 2 days, and liver functions were maintained for 3 weeks. The ammonia metabolism activities and albumin secretion activities of co-cultured cells on the CCWs were slightly inferior to those on the TCWs. This co-culture system of hepatocytes and BMCs is an appropriate culture system for the expression and maintenance of liver-specific functions in vitro, and is expected to be applicable to bioartificial liver systems, regenerative medicine, and liver function simulators. © The Japanese Society for Artificial Organs 2005.

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  • Higher viscous solution induces smaller droplets for cell-enclosing capsules in a co-flowing stream

    Shinji Sakai, Kenji Kawabata, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Biotechnology Progress   21 ( 3 )   994 - 997   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mechanical strength of cell-enclosing capsules governs the success of the transplantation of enclosed cells in vivo for cell therapy. Mechanical strength closely correlates with the concentration and molecular weight of the polymers present in the aqueous solution that end up in the capsules, and the viscosity of the aqueous polymer solution also depends on these two factors. Three aqueous solutions differing in viscosity (1.0, 36, and 194 mPa s) were extruded from a needle (300 μm inner diameter) at a velocity of 1.2 cm/s into an ambient co-flowing liquid paraffin laminar stream. Smaller droplets were obtained from a higher viscous solution. At a liquid paraffin velocity of 23.5 cm/s, the diameter of droplets obtained from the highest viscous solution (194 mPa s)) was 44 ± 4 μm, and it represented 40% and 20% of that from droplets in solutions of 36 and 1.0 mPa s viscosity, respectively. The cells enclosed in these droplets maintained more than 95% viability during the droplet breakup process independent of the viscosity of the aqueous solution (p &gt
    0.50). In addition, retrieved cells from the droplets showed the same proliferation profiles as the cells that were not subjected to the droplet breakup process, on tissue culture dishes (p &gt
    0.13). © 2005 American Chemical Society and American Institute of Chemical Engineers.

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  • Nonaggregating refolding of ribonuclease A using reverse micellar dialysis

    Tsutomu Ono, Mai Nagatomo, Tomoaki Nagao, Hiroyuki Ijima, Koei Kawakami

    Biotechnology and Bioengineering   89 ( 3 )   290 - 295   2005年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A hydrophilic ultrafiltration membrane, regenerated cellulose, facilitates the size-selectable permeability of hydrophilic solutes in reverse micellar solution. By using an ultrafiltration membrane with a molecular weight cutoff of 3,500, we demonstrate a nonaggregating protein refolding technique based on the dialysis of reverse micellar solution. This realizes concurrent removal of denaturants, urea and 2-mercaptoethanol, and the supply of redox reagents, reduced and oxidized glutathione (GSH, GSSG), to promote renaturation of proteins. Two mg/ml ribonuclease A (RNase A) was refolded completely without any dilution and aggregation for 60 h. The refolding behavior of RNase A is strongly influenced by the ratio of GSH and GSSG. Moreover, we recovered 90% of the refolded RNase A from AOT reverse micellar solution with acetone precipitation and β-cyclodextrin washing. These findings should facilitate the production of a continuous protein refolding membrane reactor. © 2004 Wiley Periodicals, Inc.

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  • Development and characterization of a silica monolith immobilized enzyme micro-bioreactor

    K Kawakami, Y Sera, S Sakai, T Ono, H Ijima

    INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH   44 ( 1 )   236 - 240   2005年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER CHEMICAL SOC  

    Several 10-cm-long capillary tubes [made of poly(ether ether ketone) (PEEK)] with inside diameters of 0.1-2.0 mm were filled with silica monolith-immobilized protease derived by in situ sol-gel transition from a 1:4 mixture of tetramethoxysilane and methyltrimethoxysilane. Transesterification between 20 mM (S)-(-)-glycidol and 0.4 M vinyl n-butyrate in an organic solvent was used as the test reaction. The substrate solution flowed through the column at a flow rate of 0.0004-5.0 mL(.)min(-1). The conversion in the micro-bioreactor was higher than that in the batch reactor at a high liquid flow rate. When three tubes were connected in series, the conversion at a fixed ratio of the mass of the enzyme to the liquid flow rate was increased by approximately 50%, because of the tripling of the flow rate as compared to the case with a single tube. Changes in the tube diameter had no influence on the conversion at a fixed superficial liquid velocity. Further, the conversion increased with a decrease in the enzyme content. These results were ascribed to the apparent effect of liquid-solid mass transfer and were analyzed quantitatively using a simple mathematical model.

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  • Transition of mechanical property of porous alginate scaffold with cells during culture period 査読

    Shinji Sakai, Hiroki Masuhara, Yusuke Yamada, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Journal of Bioscience and Bioengineering   100 ( 1 )   127 - 129   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier  

    The rupture forces of porous alginate scaffolds seeded with hepatocytes or fibroblast-like cells increased during 3 d of culture and then decreased. The phenomenon was independent of the number of viable cells within the scaffolds, but dependent on protein adsorption to the alginate as well as a reduction in the degree of crosslinks of the calcium-alginate gel. © 2005, The Society for Biotechnology.

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  • アルギン酸とオリゴキトサンからなる細胞培養担体作製法の開発

    増原 広樹, 境 慎司, 小野 努, 井嶋 博之, 川上 幸衛

    化学工学会 研究発表講演要旨集   2005   319 - 319   2005年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2005.0.319.0

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  • アミノ糖添加によるタンパク質含有リポソームの特性改変とその評価

    村上 直, 境 慎司, 小野 努, 井嶋 博之, 川上 幸衛

    化学工学会 研究発表講演要旨集   2005   204 - 204   2005年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2005.0.204.0

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  • 動物細胞包括サブシーブカプセルの性能評価

    境 慎司, 川端 賢二, 小野 努, 井嶋 博之, 川上 幸衛

    化学工学会 研究発表講演要旨集   2005   318 - 318   2005年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2005.0.318.0

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  • Behavior of enclosed sol- and gel-alginates in vivo

    S Sakai, T Ono, H Ijima, K Kawakami

    BIOCHEMICAL ENGINEERING JOURNAL   22 ( 1 )   19 - 24   2004年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE SA  

    Changes in the behavior of alginates, both non-gelled and gelled with calcium ions, in microcapsules after implantation in vivo were investigated using alginates enclosed in regenerated cellulose membrane. The mechanical properties of the alginates after soaking in simulated body fluid (SBF) and implantation in the peritoneal cavities of animals were determined. A stress-compression study on specimens soaked in SBF showed that the alginates in the microcapsules would have almost the same mechanical properties after several days of implantation independent of whether the enclosed alginate was non-gelled or gelled with calcium ions before implantation. The stresses at a particular compression point decreased with increasing incubation period for 3-6 days for the alginates gelled with calcium ions before soaking in SBR In contrast, these values increased over the same period for the non-gelled alginates before soaking in SBR In agreement with the results of the in vitro study, no significant differences were observed between the mechanical properties of the non-gelled and gelled alginates retrieved from the peritoneal cavities of DDY mice after 1 week of implantation. (C) 2004 Elsevier B.V. All rights reserved.

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  • Hydroxyapatite for use as an animal cell culture substratum obtained by an alternate soaking process 査読

    Hiroyuki Ijima, Tomokazu Ohchi, Tsutomu Ono, Koei Kawakami

    Biochemical Engineering Journal   20 ( 2-3 )   155 - 161   2004年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hydroxyapatite (HAp), the major inorganic component of hard tissues in vivo, was formed in/on a PVA gel. The HAp formation ratio depended on the reaction cycle number, but was independent of the alternate soaking period per cycle. The Ca/P molar ratio of HAp formed at 10 reaction cycles was very close to the theoretical value of HAp, 1.67. CHO-K1 cell adhesion, proliferation and maximum cell density on HAp plates were better on plates formed at two or five reaction cycles using 200 mM CaCl2 and 120 mM Na2HPO 4 solutions than on plates formed under other conditions. Furthermore, the adhesion ratio of CHO-K1 cells on HAp plates formed at 10 reaction cycles was about 60% of those at two or five reaction cycles. © 2003 Elsevier B.V. All rights reserved.

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  • Preparation of Mammalian Cell-Enclosing Subsieve-Sized Capsules (&lt; 100 μm) in a Coflowing Stream

    Shinji Sakai, Kenji Kawabata, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Biotechnology and Bioengineering   86 ( 2 )   168 - 173   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The droplet breakup technique with an immiscible liquid coflowing stream was investigated for the preparation of mammalian cell-enclosing subsieve-sized capsules of less than 100 μm in diameter. The major parts of the droplet generation device were a needle of several hundred micrometers in diameter for extruding the cell-suspending sodium alginate aqueous solution and a tubule of 2.5 mm in diameter through which the extruded alginate solution flowed into ambient immiscible liquid paraffin. The needle was positioned upstream in the vicinity of the coaxial tubule. The droplet diameter of the viscous sodium alginate aqueous solution could be controlled from several dozen to several hundred micrometers by changing the velocities of the inner and ambient fluids and the diameter of the needle. By utilizing a 300-μm diameter needle, CHO-K1 cell-enclosing droplets of 48 ± 8 μm in diameter were obtained by extruding a cell-suspending sodium alginate solution at a velocity of 1.2 cm/sec into the ambient liquid paraffin flowing at a velocity of 23.5 cm/sec. The breakup process did not influence the viability of the enclosed cells, since more than 95% of the CHO-K1 cells remained alive after the enclosing process. © 2004 Wiley Periodicals, Inc.

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  • Hydrothermal synthesis of porous hydroxyapatite plates from gypsum: Use as an animal cell culture substratum 査読

    Hiroyuki Ijima, Motonori Nakashima, Sachiko Furuta, Tsutomu Ono, Koei Kawakami

    Journal of Chemical Engineering of Japan   37 ( 4 )   531 - 535   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A macroporous HAp culture substratum was formed by hydrothermal treatment of gypsum. The macropores derived from poly(methylmetacrylate) (PMMA) beads had diameters of 150-200 μm, and a porosity of 28% that was dependent on the PMMA beads quality. The maximum CHO-K1 cell density of the macroporous HAp microcarrier was 7.3 × 107 cells·m/-1-HAp. This value is similar to most existing suitable porous microcarriers. A macroporous HAp plate packed-bed type bioreactor was designed. The density of CHO-K1 cells in the bioreactor was seven times higher than that from a stationary culture. These results suggest that the HAp synthesized from gypsum by hydrothermal treatment is a suitable animal cell culture substratum. © 2004 The Society of Chemical Engineers, Japan.

    DOI: 10.1252/jcej.37.531

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  • MIN6 cells-enclosing aminopropyl-silicate membrane templated by alginate gels differences in guluronic acid content

    S Sakai, T Ono, H Ijima, K Kawakami

    INTERNATIONAL JOURNAL OF PHARMACEUTICS   270 ( 1-2 )   65 - 73   2004年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Mouse insulinoma (MIN6) cells were encapsulated into aminopropyl-silicate membrane deposited on calcium alginate gel beads via the sol-gel synthesis. Two alginates with different guluronic acid (G) contents, high and intermediate, but with the same molecular weights were used. Viability of the cells in the membrane templated by the alginate with an intermediate content of guluronic acid (intermediate-G) was approximately 10% higher than those in the membrane templated by the alginate with a high content of guluronic acid immediately after encapsulation. Growth of cells in vitro was hindered in case of encapsulation in the aminopropyl-silicate membrane deposited on the high-G alginate gel. The MIN6 cells in the-microcapsule made from high-G alginate needed a longer period to establish a normoglycemic in recipients than those in the microcapsule made from intermediate-G alginate despite the same number of viable cells implantation. Recipients of the microcapsule with the core made from the intermediate-G alginate maintained their blood glucose values less than 300 mg/dl for a longer period. (C) 2003 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ijpharm.2003.10.014

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  • Development of co-culture system of hepatocytes with bone marrow cells for expression and maintenance of hepatic functions 査読

    S. Murakami, Hiroyuki Ijima, T. Ono, K. Kawakami

    International Journal of Artificial Organs   27 ( 2 )   118 - 126   2004年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In this study, a co-culture system of hepatocytes and bone marrow cells (BMCs) was developed and characterized for the expression and maintenance of ammonia metabolism and albumin secretion activities. A culture medium supplemented with epidermal growth factor, insulin, L-proline, hydrocortisone and 20 % (v/v) heat-inactivated fetal bovine serum was developed. In addition to adhesive bone marrow cells, the co-existence of non-adhesive bone marrow cells was effective in expressing liver-specific functions for at least 3 weeks. On the other hand, experiments with Transwell in which cultured cells were separated by a semi-permeable membrane, suggested that soluble factors secreted by BMCs are the key components in the functional enhancement of cells. Furthermore, direct contact between hepatocytes and BMCs enhanced the formation of spheroids and the expression of liver specific functions. These results indicate that this co-culture system is promising in, for example, bioartificial liver, regenerative medicine, and liver function simulator applications. © Wichtig Editore, 2004.

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  • Proliferation and insulin secretion function of mouse insulinoma cells encapsulated in alginate/sol-gel synthesized aminopropyl-silicate/alginate microcapsule

    S Sakai, T Ono, H Ijima, K Kawakami

    JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY   28 ( 2 )   267 - 272   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC PUBL  

    Alginate/aminopropyl-silicate/alginate microcapsules, ca. 15 mum in membrane thickness and ca. 500 mum in diameter, were prepared via sol-gel process. The aminopropyl-silicate membrane was derived from two silicone alkoxide precursors, tetramethoxysilane and 3-aminopropyl-trimethoxysilane on Ca-alginate micro gel beads. Pancreatic beta-cell line (MIN6) cells were encapsulated in the microcapsule. The encapsulated MIN6 cells proliferated and formed spheroidal tissues in vitro. The diameter of the MIN6 spheroids increased to approximately 250 mum with an increase in the incubation period until the day 35. Storeptozotocin-induced diabetic mice became normoglycemia after implantation of the MIN6-enclosing microcapsules. The normoglycemic state remained until the retrieval of the implanted microcapsules for 1 month. These results indicate that the potential use of the alginate/aminopropyl-silicate/alginate microcapsule as a vehicle for a genetically engineered cell-enclosing therapeutic material delivery system.

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  • Enhancement of protease activity in transesterification of glycidol with vinyl n-butyrate by entrapment into alkyl-substituted silicates and pretreatment with a substrate 査読

    Koei Kawakami, Yoshiaki Matsui, Tsutomu Ono, Hiroyuki Ijima

    Biocatalysis and Biotransformation   21 ( 1 )   49 - 52   2003年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Proteases originating from Aspergillus melleus (Protease P) and Bacillus subtillis (Prolether FG-F) were entrapped into organic-inorganic hybrid silicates on Celite 545 by the sol-gel method, and their activities measured at 35° C for transesterification of chiral glycidol with vinyl n-butyrate in isooctane. n-Butyl- and dimethyl-substituted silicates provided 12.6 times higher activities with Protease P and 5.5 times with Prolether FG-F, respectively, than those deposited on Celite 545. Although pretreatment of those immobilized proteases with the chiral glycidol affected transesterification activities of both enantiomers, the ratio of the initial transesterification rate of (S)-(-)-glycidol to that of (R)-(+)-glycidol, remained unchanged.

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  • Modification of porous aminopropyl-silicate microcapsule membrane by electrically-bonded external anionic polymers

    Shinji Sakai, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Journal of Biomaterials Science, Polymer Edition   14 ( 7 )   643 - 652   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Biocompatibility and permeability of a microcapsule membrane governs the function of a microcapsule-shaped bioartificial pancreas. We have previously developed an alginate/sol-gel-synthesized aminopropyl-silicate/alginate microcapsule (Alg/AS/Alg), which had insufficient biocompatibility. The purpose of this study was to investigate whether the biocompatibility could improve by modifying the external surface with other anionic polymers and to investigate an influence of the modification on the permeability of the membrane. Four kinds of anionic polymers, poly(oxyethylene)diglycolic acid (3 kDa), heparin (15 kDa), Alg (54 kDa) and carboxymethylcellulose (CMC, 60 kDa) were used as the external anionic polymers. The heparin-bonded gel bead had the largest resistance to the diffusion of small molecules. The molecular mass cut-off point of 150 kDa required for immunoisolation was maintained for all anionic polymers. Cellular overgrowth to the implanted islet-enclosing microcapsule, a sign of insufficient biocompatibility, was suppressed by altering the external surface material from Alg to CMC. These results suggest that the biocompatibility of the Alg/AS/anionic polymer membrane can be improved by using a biocompatible anionic polymer. At the same time, it is suggested the influence on the permeability has to be investigated to develop an optimal microcapsule for bioartificial pancreas.

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  • 膜型反応器を用いた蛋白質リフォールディング挙動

    小野 努, 百崎 達朗, 井嶋 博之, 川上 幸衛

    化学工学会 研究発表講演要旨集   2003   599 - 599   2003年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2003f.0.599.0

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  • Permeability of alginate/sol-gel synthesized aminopropyl-silicate/alginate membrane templated by calcium-alginate gel

    S Sakai, T Ono, H Ijima, K Kawakami

    JOURNAL OF MEMBRANE SCIENCE   205 ( 1-2 )   183 - 189   2002年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    An alginate/aminopropyl-silicate/alginate membrane was prepared on calcium-alginate gel beads via electrostatic interaction and sol-gel processes. The effects of the chemical composition and the molecular weight (MW) of the core alginate on the permeability of the alginate/aminopropyl-silicate/alginate membrane were investigated for five different types of alginates. Our data shows that an immunoisolatable MW cut-off point was achieved for the membranes formed on the alginates, MW = 7.0 x 10(4) with molar ratio of M/G (mannuronic acid to guluronic acid), M/G = 1.30, MW = 1.1 X 10(5) with M/G = 1.30, and MW = 7.0 x 10(4) with M/G = 0.65. For these three membranes, the membrane templated by the alginate of MW = 1.1 x 10(5) had a higher MW cut-off point than that templated by the alginate of MW = 7.0 x 10(4). In addition, the MW cut-off point increased with an increase in the content of guluronic acid. The membranes formed on the alginates of MW = 2.0 x 10(4) with M/G = 1.30, and MW = 7.0 x 10(4) with M/G = 2.25 did not have an immumoisolatable MW cut-off point. (C) 2002 Elsevier Science B.V. All rights reserved.

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  • Aminopropyl-silicate membrane for microcapsule-shaped bioartificial organs: control of molecular permeability

    S Sakai, T Ono, H Ijima, K Kawakami

    JOURNAL OF MEMBRANE SCIENCE   202 ( 1-2 )   73 - 80   2002年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    A novel microcapsule membrane composed of aminopropyl-silicate was synthesized on Ca-alginate gel beads from 3-aminopropyltrimethoxysilane (APTrMOS) and tetramethoxysilane (TMOS) by the sol-gel method. Preparation conditions such as the molar ratio of APTrMOS to TMOS, the sequence of addition and the contact time of each precursor were examined to give the membrane immunoisolatable permeability for microcapsule-shaped bioartificial organs. The permeability of the membrane decreased with an increase of up to 2.4 in the molar ratio, with gamma-globulin being completely rejected at this ratio. Addition of APTrMOS prior to TMOS and allowing 1 min of contact with the Ca-alginate gel beads suspended in n-hexane was effective for rejection of gamma-globulin. The optimized aminopropyl-silicate membrane was estimated to give a molecular weight cut-off point of less than 150 kDa, as required for immunoisolation, and an excellent permeability to low molecular weight substances such as glucose and oxygen. Our data show that the permeability of the aminopropyl-silicate membrane, that is the microscopic structure of the membrane, is strongly controllable by altering preparation conditions. (C) 2002 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0376-7388(01)00731-1

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  • Permeability of a sol-gel synthesized aminopropyl-silicate-titanate hybrid membrane for the microcapsule-shaped bioartificial pancreas

    S. Sakai, T. Ono, H. Ijima, K. Kawakami

    Journal of Artificial Organs   Vol.5, pp.54-59, 2002   54 - 59   2002年4月

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    The aminopropyl-silicate-titanate hybrid membrane was successfully synthesized onto a Ca-alginate gel bead by the sol-gel method, from two kinds of organometallic compound precursors, tetraethyl orthotitanate (TEOTi) [Ti(OC2H5)4] and 3-aminopropyltrimethyl orthosilicate (APTrMOS) [(CH3O)3Si(CH2)3NH2]. APTrMOS acted as a binding agent between inorganic titanate and alginate polymer via electrostatic interaction between amino groups of APTrMOS and carboxyl groups of alginate. From the measurements of the diffusion of ovalbumin and γ-globulin through the aminopropyl-silicate-titanate hybrid membrane, it was found that the molecular permeability of the membrane could be controlled by changing the amount of each precursor. The molecular weight cutoff point required for immunoisolation, less than 150kDa, was achieved under the condition that the amount of APTrMOS was 3.40 mmol/ (10 ml of Ca-alginate) and TEOTi was more than 1.42 mmol. The islets encapsulated in the membrane showed almost the same insulin secretion viability as the free islets.

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  • Effect of imprinting sol-gel immobilized lipase with chiral template substrates in esterification of (R)-(+)- and (S)-(-)-glycidol

    Shin-Ya Furukawa, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Journal of Molecular Catalysis - B Enzymatic   17 ( 1 )   23 - 28   2002年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To prepare an immobilized lipase effective for enantioselective esterification of glycidol with n-butyric acid in organic media, hybrid gel-entrapped lipase on Celite was prepared by the sol-gel method and pretreated with chiral template substrates. When n-butyltrimethoxysilane, (n-BuTrMOS) as an organic silane precursor, was mixed with tetramethoxysilane (TMOS) at a molar ratio of 4:1, the hybrid gel-entrapped lipase on Celite showed three times higher activity than the deposited lipase on Celite as a control. The pretreatment of this immobilized lipase with a hydrophobic enantiomer such as (R)-(-)-2-octanol brought about a selective enhancement of the activity for the esterification of (R)-(+)-glycidol, whereas such pretreatment hardly affected the activity for the esterification of (S)-(-)-glycidol. Consequently, the relative initial enantiomeric activity (RIEA) of the hybrid gel-entrapped lipase on Celite, defined as a ratio of the initial esterification rate of (R)-(+)-glycidol to that of (S)-(-)-glycidol, changed between 0.76 and 2.0. In addition, increasing the concentration of (R)-(-)-2-octanol as a template substrate, increased the activity and RIEA, and showed maximum values with the addition of 21mM of (R)-(-)-2-octanol. Copyright © 2002 Elsevier Science B.V.

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  • Activation of protease by sol-gel entrapment into organically modified hybrid silicates 査読

    S Furukawa, T Ono, H Ijima, K Kawakami

    BIOTECHNOLOGY LETTERS   24 ( 1 )   13 - 16   2002年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KLUWER ACADEMIC PUBL  

    To prepare an immobilized protease with a high activity for transesterification of vinyl n-butyrate with 3-methyl-1-butanol (isoamyl alcohol) in organic media, a protease was entrapped into organic-inorganic hybrid silica gel on Celite 545 by the sol-gel method. When propyltrimethoxysilane was used as the organic silane precursor mixed with tetramethoxysilane at a molar ratio of 16:1, the hybrid gel-entrapped protease on Celite 545 had 8 times the activity of the protease deposited on Celite 545 from 35 to 85 degreesC.

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  • Alginate/aminopropyl-silicate/alginate membrane immunoisolatability and insulin secretion of encapsulated islets

    Shinji Sakai, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Biotechnology Progress   18 ( 2 )   401 - 403   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We utilized the sol-gel reaction to prepare an immunoisolatable membrane for a microcapsule-shaped bioartificial pancreas. The membrane, derived from two precursors, 3-(aminopropyl)trimethoxysilane (APTrMOS) and tetramethoxysilane (TMOS), was formed onto calcium-alginate gel beads via electrostatic interaction. The molecular weight cutoff point of less than 150 000 required for immunoisolation was achieved at molar ratios ([APTrMOS]/[TMOS]) ranging from 0.60 to 2.40 with the amount of APTrMOS fixed at 3.40 mmol/(10 mL of calcium-alginate). When encapsulated in a membrane prepared at the molar ratio of 0.60, the islets contracted in volume and showed no response to stimulation by a high glucose concentration. However, islets in a membrane prepared at the molar ratio of 2.40 showed no contraction and responded to the glucose stimulation at almost the same level as free islets. These results demonstrated that the molar ratio of the precursors was a dominant factor affecting membrane permeability and the insulin secretion activity of the encapsulated islets.

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  • In vitro and in vivo evaluation of alginate/sol-gel synthesized aminopropyl-silicate/alginate membrane for bioartificial pancreas 査読

    Shinji Sakai, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Biomaterials   23 ( 21 )   4177 - 4183   2002年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Alginate/aminopropyl-silicate/alginate (Alg/AS/Alg) membrane was prepared on Ca-alginate gel beads by a sol-gel process. The membrane has ≡Si-O-Si≡ bonds as well as electrostatic bonds between amino groups of AS and carboxyl groups of alginate. Permeability and stability were investigated for the membrane. Furthermore, rat islets encapsulated in the membrane (499±32μm in diameter, 1000 islets/recipient) were transplanted to the peritoneal cavities of the mice with streptozotocin-induced diabetes. Our data show that the membrane had the molecular weight cut-off point of between 70 and 150kDa, and hardly inhibited the permeation of glucose and insulin. The Alg/AS/Alg microcapsule was more stable than the well-known Alg/poly-L-lysine (PLL)/Alg microcapsule. After 30 days of soaking in stimulated body fluid, the percentages of intact microcapsule were 98.4±0.5 (mean±SEM)% and 88.0±1.5% (p&lt
    0.001) for the Alg/AS/Alg and Alg/PLL/Alg microcapsules, respectively. The maximum maintenance period of normoglycemia was 105 days without administration of immunosuppressive drugs. Copyright © 2002 Elsevier Science Ltd.

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  • Control of transport characteristic of membrane by multi-layering of polyelectrolyte complex toward microcapsule-shaped bioartificial pancreas

    Shinji Sakai, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Kagaku Kogaku Ronbunshu   Vol.27, No.2, pp.165-168   168   2001年12月

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    In order to develop a microcapsule-shaped bioartificial pancreas, it is important to control the transport characteristics of the semipermeable membrane. We attempt to control the transport characteristics of the membrane by changing the coating layer number of polyelectrolyte complex between glycol chitosan (GC, M. W.&gt;8.2×10 4) and alginate (Alg) on the microcapsule. From measurement of diffusivities of bovine serum albumin (BSA, M. W.=6.7×10 4) and γ-globulin (M. W. = 1.6×10 5), these diffusion rates through the membrane drastically decrease with increasing layer number of GC-Alg. The microcapsule coated with four layers of polyelectrolyte complex successfully rejects γ-globulin with effective permeability of BSA. In addition, the diffusivity of glucose (M. W.=180) indicateds that the multi-layering of polyelectrolyte complex hardly affects the diffusivity of small substances such as nutrients and oxygen. These results indicate that the polyelectrolyte complex prepared by the multilayering method is useful to control the transport characteristic of membranes and the four-layered GC -Alg polyelectrolyte complex microcapsule is promising for a microcapsule-shaped bioartificial pancreas.

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  • Synthesis and transport characterization of alginate/aminopropylsilicate/alginate microcapsule: application to bioartificial pancreas 査読

    S Sakai, T Ono, H Ijima, K Kawakami

    BIOMATERIALS   22 ( 21 )   2827 - 2834   2001年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    To develop a novel type of immunoisolation membrane for a microcapsule-shaped bioartificial pancreas, we attempted to use a sol-gel synthesized silicate. An aminopropyl-silicate membrane derived from 3-aminopropyltrimethoxysilane and tetramethoxysilane was formed on Ca-alginate gel beads via electrostatic interaction. The positively charged amino groups remaining on the surface of the resultant gel beads were neutralized by immersion in an aqueous Na-alginate solution. From measurements of the partition coefficients and effective diffusivities of different substances to the gel beads, it was found that the aminopropyl-silicate membrane prepared under optimized composition of silicon alkoxide precursors successfully rejected gamma -globulin, giving good permeability to substances having a low molecular weight. Islets could be encapsulated within the newly developed microcapsules while retaining their ability to secrete insulin. (C) 2001 Elsevier Science Ltd. All rights reserved.

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  • Enhancement of activity of sol-gel immobilized lipase in organic media by pretreatment with substrate analogues

    Shin-Ya Furukawa, Tsutomu Ono, Hiroyuki Ijima, Koei Kawakami

    Journal of Molecular Catalysis - B Enzymatic   15 ( 1-3 )   65 - 70   2001年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    By performing pretreatment with substrate analogues, an activation of lipase immobilized into organic-inorganic hybrid silicate was attempted in esterification of menthol with butyric acid in organic media. With decreasing water content of immobilized lipase preparations, the activity of immobilized lipases by (-)-menthol pretreatment was enhanced, and the highest activity was obtained at water activity, aw=0.11. However, the pretreatment of immobilized lipases with (-)-menthol could not improve the enantioselectivity. In addition, the activity of pretreated immobilized lipases increased with increasing the chain length of alcohol as a substrate analogue. Consequently, it was found that hydrophobic and bulky alcohol was an effective substrate analogue to activate immobilized lipases. Copyright © 2001 Elsevier Science B.V.

    DOI: 10.1016/S1381-1177(01)00007-8

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  • Evaluating the performance of a hybrid artificial liver support system with a recoverable hepatic failure rat model 査読

    Hiroyuki Ijima, Ayako Noguchi, Takeyuki Katsuno, Tsutomu Ono, Kohji Nakazawa, Kazumori Funatsu, Koei Kawakami

    Annals of the New York Academy of Sciences   944   344 - 349   2001年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:New York Academy of Sciences  

    To evaluate the performance of an artificial liver, we created a recoverable hepatic failure rat model. This involves a 30-60 minute warm ischemia, via clamping, of one-third of the liver with a partial (two-thirds) hepatectomy. Variations on this method provide for the possibility of several modes of hepatic failure. Survival time of the rats was prolonged (35%) by applying our hybrid artificial liver. However, the extracorporeal circulation is a considerable burden to the rat. Therefore, we need to apply the hybrid artificial liver intermittently and repeatedly.

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  • Newly developed aminopropyl-silicate immunoisolation membrane for a microcapsule-shaped bioartificial pancreas 査読

    S Sakai, T Ono, H Ijima, K Kawakami

    BIOARTIFICIAL ORGANS III: TISSUE SOURCING, IMMUNOISOLATION, AND CLINICAL TRIALS   944   277 - 283   2001年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NEW YORK ACAD SCIENCES  

    An aminopropyl-silicate membrane, synthesized from tetramethoxysilane (TMOS) and 3-aminopropyltrimethoxysilane (APTrMOS) by the sol-gel method, was formed onto Ca-alginate gel beads via electrostatic interactions. The permeability of the membrane could be controlled easily by changing the molar ratio of both the precursors ([APTrMOS]/[TMOS]). The aminopropyl-silicate membrane prepared at a molar ratio of 2.40 rejected gamma-globulin and BSA successfully, whereas it permeated ovalbumin. This result indicates that the molecular weight cutoff point of this newly developed aminopropyl-silicate membrane is approximately 60 kDa.

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書籍等出版物

  • 撹拌技術とスケールアップ、シミュレーションの活用

    渡邉貴一, 小野努( 担当: 分担執筆 ,  範囲: 第2章「撹拌機の設計と運転条件の最適化」第18節, 182–187 (2021))

    技術情報協会  2021年11月  ( ISBN:9784861048647

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    総ページ数:532p   記述言語:日本語

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  • マイクロ流路内で形成される単分散な水性二相系液滴を利用したハイドロゲルマイクロカプセルの調製 招待

    混相流   34 ( 2 )   318 - 325   2020年6月

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    担当区分:最終著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

    DOI: 10.3811/jjmf.2020.t007

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  • 金属膜で包まれた液体”金属被覆マイクロカプセル”の開発 招待

    小野努, 渡邉貴一

    C & I Commun   45 ( 3 )   30 - 33   2020年3月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • マイクロ流体デバイスによる精密コロイド材料調製のための界面設計 招待

    小野努, 渡邉貴一

    粉体工学会誌   55   340 - 345   2018年6月

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    担当区分:筆頭著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • マイクロ流体デバイスを用いた単分散ポリ乳酸微粒子の連続調製 招待

    渡邉貴一, 小野努

    ケミカルエンジニヤリング   63 ( 2 )   2018年2月

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    担当区分:最終著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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  • マイクロ流路内のスラグ流を利用した無乳化重合による微粒子調製 (特集 反応場コントロール技術の最前線)

    小野 努

    化学工学   78 ( 7 )   477 - 479   2014年7月

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    担当区分:筆頭著者   記述言語:日本語   出版者・発行元:化学工学会  

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  • マイクロ流路を用いた微細液滴調製に関する研究動向

    渡邉貴一, 小野努

    化学工学会誌   76 ( 12 )   781 - 782   2012年12月

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    担当区分:最終著者   記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • 高度に制御された巨大孔を有するマイクロカプセルの調製と応用

    Eiji Kamio, Tsutomu Ono

    ケミカルエンジニヤリング   54, 518-524   2009年6月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(学術雑誌)  

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  • 水性二相系を利用したW/W/Oエマルションの調製

    安川 政宏, 神尾 英治, 小野 努

    化学工学会 研究発表講演要旨集   2008 ( 0 )   643 - 643   2008年

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    記述言語:日本語   出版者・発行元:公益社団法人 化学工学会  

    DOI: 10.11491/scej.2008f.0.643.0

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  • Fabrication of a silica monolith micro-bioreactor entrapping highly activated lipase by a two-step sol-gel method

    K. Kawakami, D. Abe, T. Urakawa, S. Sakai, T. Ono, H. Ijima

    CHISA 2006 - 17th International Congress of Chemical and Process Engineering   2006年12月

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    Micro-bioreactors are effective for high throughput production of expensive products from small amounts of substrates. Lipases are versatile enzymes for chiral syntheses, and highly activated when immobilized in alkyl-substituted silicates by the sol-gel method. For application of the immobilized lipases to a continuous-flow system, a micro-bioreactor loaded with a macroporous silica monolith is well suited, because it can easily be integrated with a separator for optical resolution. We attempted to develop a micro-capillary bioreactor containing a silica monolith-immobilized lipase. A silica monolith without shrinkage during lyophilization of the hydrogel was first formed from a 1:4 mixture of tetramethoxysilane (TMOS) and methyltrimethoxysilane (MTMS). It was then coated with silica precipitates entrapping lipase, derived from a 1:4 mixture of TMOS and n-butyltrimethoxysilane (BTMS). As a result, the monolith treated with the BTMS-based silica entrapping lipase, exhibited approximately ten times higher esterification activity than the non-treated monolith-immobilized lipase derived from the MTMS-based silica.

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  • Peroxidative catalytic behavior of cytochrome c solubilized in reverse micelles

    Tsutomu Ono, Masahiro Goto

    Biochemical Engineering Journal   28 ( 2 )   156 - 160   2006年2月

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    記述言語:英語  

    Solubilization of horse heart cytochrome c into reverse micelles, a self-assembled nanostructure composed of sodium di-2-ethylhexyl sulfosuccinate (AOT), enhances the peroxidase activity in the presence of hydrogen peroxide. The catalytic activity of cytochrome c hosted in reverse micellar solution is 10-fold higher than that in water, and which depends on Wo, a molar ratio of water to AOT, and pH in aqueous droplets. In addition, the fluorescence intensity based on the tryptophan residue and the visible absorption identifying the axial Met 80-Fe bond imply that the reverse micellar solubilization induces the cleavage of the heme crevice and thus enables the formation of peroxidase-like peroxide-heme complexes. These results suggest that cytochrome c solubilized in reverse micelles provides a homogeneous catalyst as peroxidase available in organic media. © 2005 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bej.2005.10.005

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  • Mammalian cell encapsulation in monodisperse subsieve-sized (&lt;100 μm) capsules

    S. Sakai, K. Kawabata, T. Ono, H. Ijima, K. Kawakami

    Transactions - 7th World Biomaterials Congress   1510   2004年12月

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    A method for preparing monodisperse mammalian cell-enclosing subsieve-sized microcapsules from viscous polymer solution was developed. The droplet breakup technique with an immiscible liquid coflowing stream was applied for the preparation of subsieve-sized mammalian cell-enclosing capsules. The reaction was found to enhance cell viability due to reduced resistance to the transport of oxygen, nutrients and metabolites. Mechanical strength and biocompatibility were also found to be enhanced.

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  • DNA extraction by cationic reverse micelles

    Masahiro Goto, Ayumi Momota, Tsutomu Ono

    Journal of Chemical Engineering of Japan   37 ( 5 )   662 - 668   2004年5月

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    記述言語:英語  

    Deoxyribonucleotide (DNA) was successfully extracted in a few hours by reverse micelles, which were formed and functionalized by a cationic quaternary ammonium surfactant in isooctane. Several parameters which affect the DNA transfer from an aqueous phase to a reverse micellar phase, such as the natures of a surfactant and a solvent, salt concentration in a feed solution, and hydrophobicity of micelles, were investigated. The use of a cationic surfactant was found to yield a high transfer rate of DNA into reverse micelles. We have attributed the DNA transfer to the electrostatic interaction between the cationic surfactant and the negatively charged DNA. We found that the higher the hydrophobicity of a surfactant used to form micelles, the better the DNA transfer efficiency in the forward extraction. Preferential extraction of DNA was achieved by using twin long-alkyl chains of cationic surfactants. However, pH in the aqueous feed solution did not affect the extraction performance of reverse micelles. On the other hand, alcohol, as a co-solvent plays an important role in the back extraction of DNAs. Complete back-extraction of DNAs was achieved without any conformational change by adding an appropriate alcohol to the reverse micellar phase. © 2004 The Society of Chemical Engineers, Japan.

    DOI: 10.1252/jcej.37.662

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  • ナノ空間で起こる逆ミセルの生化学反応とその応用

    バイオサイエンスとインダストリー   60 ( 11 )   747 - 750   2002年

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  • Catalytic oxidation of o-phenylenediamine by cytochrome c encapsulated in reversed micelles

    T Ono, K Kawakami, M Goto, S Furusaki

    JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC   11 ( 4-6 )   955 - 959   2001年1月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Cytochrome c solubilized in reversed micelles formulated with di-2-ethylhexyl sulfosuccinate (AOT) has allowed to catalyze the oxidation of o-phenylenediamine (o-PDA) with hydrogen peroxide. The oxidative reaction did not occur effectively by cytochrome c in water. The nanostructural environment in reversed micelles seemed to perturb the three-dimensional structure of the active site of cytochrome c. The product obtained in reversed micelles had a specific absorption spectrum with the absorption peak at 720 nm, indicating a blue-colored solution, whereas common peroxidases such as horseradish peroxidase provided a yellow-colored product in water with the absorption peak at 420 nm. The difference in the oxidative products suggests that AOT molecules play an important role in the specificity of o-PDA oxidation. The dependency of the product species on the pH of the inner droplet in reversed micelles indicated that the specific oxidative product was prepared by electrostatic interaction with AOT molecules. (C) 2001 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S1381-1177(00)00173-9

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  • 生体分子とナノ集合体の融合による新機能発現

    化学工業   52 ( 3 )   192 - 197   2001年

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  • 逆ミセルによるキモトリプシンの選択的抽出

    Masahiro Goto, Maki Korenaga, Tsutomu Ono, Shintaro Furusaki

    化学工学論文集   27 ( 2 )   181 - 185   2001年

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    記述言語:英語  

    Extraction behavior of active and denatured α-chymotrypsin is investigated by the reversed micellar extraction technique. The anionic surfactant dioleyl phosphoric acid (DOLPA) selectively extracted the active protein over the denatured protein. However, the reversed micelles using AOT do not afford selectivity. Based on the difference in the structural properties between the active and the heated α-chymotrypsin, the extraction behavior by the DOLPA reversed micelles is discussed. Key words: extraction, reverse micelle, surfactant, protein separation, AOT. © 2001, The Society of Chemical Engineers, Japan. All rights reserved.

    DOI: 10.1252/kakoronbunshu.27.181

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  • Important parameters affecting efficiency of protein refolding by reversed micelles

    M Goto, Y Hashimoto, T Fujita, T Ono, S Furusaki

    BIOTECHNOLOGY PROGRESS   16 ( 6 )   1079 - 1085   2000年11月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    Refolding of denatured RNase A as a model of inclusion bodies was performed by reversed micelles formulated with sodium di-2-ethylhexyl sulfosuccinate (AOT) in isooctane. In the novel refolding process, a solid-liquid extraction was utilized as an alternative to the ordinary protein extraction by reversed micelles based on a liquid-liquid extraction. First, the effects of operational parameters such as concentration of AOT, W-o (= [H2O]/[AOT]), and pH were examined on the solubilization of solid denatured proteins into a reversed micellar solution. The solubilization was facilitated by a high AOT concentration, a high W-o value, and a high pH in water pools. These conditions are favorable for the dispersion of the solid protein aggregates in an organic solvent. Second, the renaturation of the denatured RNase A solubilized into the reversed micellar solution was conducted by addition of glutathione as a redox reagent. A complete renaturation of RNase A was accomplished by adjusting the composition of the redox reagent even at a high protein concentration in which protein aggregation would usually occur in aqueous media. In addition, the renaturation rates were improved by optimizing water content (W-o) and the pH of water pools in reversed micelles. Finally, the recovery of renatured RNase A from the reversed micellar solution was performed by adding a polar organic solvent such as acetone into the reversed micellar solution. This precipitation method was effective for recovering proteins from reversed micellar media without any significant reduction in enzymatic activity.

    DOI: 10.1021/bp000073m

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  • Catalytic capabilities of lipase immobilized into organically modified silicates by sol-gel method

    SY Furukawa, T Ono, H Ijima, K Kawakami

    KAGAKU KOGAKU RONBUNSHU   26 ( 6 )   882 - 886   2000年11月

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    記述言語:日本語   出版者・発行元:SOC CHEMICAL ENG JAPAN  

    The capabilities of Candida rugosa lipase, which was immobilized into organically modified silicates formed on kieselguhr such as Celite 545 are investigated in esterification of (-)- or (+)-menthol with butyric acid. In this study, we optimized the preparation conditions such as a molar ratio of precursors. From these investigations, we find that the optimized hybrid gel-immobilized lipase is derived from a mixture of dimethyldimethoxysilane and tetramethoxysilane at a molar ratio of 4 : 1 and its enantioselectivity, which is defined as a ratio of the initial reaction rate of (-)-menthol to that of (+) -menthol, is enhanced up to 41 at 75 degreesC. In addition, we observe the temperature dependence of these immobilized lipases. Consequently, the optimized hybrid gel-immobilized lipase shows higher activity than deposited lipase on Celite at all temperatures, and it is suggested that this activation results from a remarkable enhancement of the V-max value.

    DOI: 10.1252/kakoronbunshu.26.882

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  • Control of molecular weight cut-off for immunoisolation by multilayering glycol chitosan-alginate polyion complex on alginate-based microcapsules

    S Sakai, T Ono, H Ijima, K Kawakami

    JOURNAL OF MICROENCAPSULATION   17 ( 6 )   691 - 699   2000年11月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Glycol chitosan is a positively charged polysaccharide which is water-soluble at pH 7.4, and is able to form a polyion complex (PIC) with anionic polymers, such as alginate. The authors attempt to develop a novel type of alginate-based microcapsule using this glycol chitosan for a islets-encapsulated bioartificial pancreas. The number of layers composed of glycol chitosan-alginate (GC-Alg) PIC were optimized, in order to cut off immunoglobulin transport and to protect encapsulated islets from the host immune reaction, and the transport characteristics were evaluated of glucose, bovine serum albumin (BSA) and gamma-globulin. To add mechanical stability to the microcapsule, calcium ions, which crosslinked the alginate polymers close to the interface between core Ca-alginate and multilayered membrane, were partially substituted with barium ions after the formation of multilayered Ca-alginate gel beads. The partition coefficients of BSA and gamma-globulin were decreased with the increasing number of layers. The immunoisolation was achieved against gamma-globulin with four layers of the GC-Alg PIC membrane, while BSA could permate the membrane. The foul-layered Ba-alginate gel bead had a good permeability for glucose, giving a diffusion coefficient corresponding to 80% of that in pure water. Insulin secretion from the islets in the four-layered Ba-alginate microcapsule was satisfactorily observed with the fractional stimulation ratio of 2.17. This result indicates that the encapsulated islets maintained their viability even after encapsulation. It was, thus, shown that the Ba-alginate microcapsule with four layers of the GC-Alg PIC membrane is promising as the microencapsulation material for a bioartificial pancreas.

    DOI: 10.1080/02652040050161684

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  • Reversed micelles as novel protein refolding media

    ACS Symp. Series   740   374 - 383   2000年

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  • ゾルーゲル法により調製した有機-無機ハイブリッドシリカ固定化リパーゼの触媒性能

    化学工学論文集   26 ( 6 )   882 - 886   2000年

  • 機能性流体逆ミセルのバイオ分野への応用

    ケミカルエンジニアリング   54 ( 6 )   418 - 424   2000年

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  • 逆ミセルによるタンパク質および核酸の抽出分離

    後藤雅宏, 小野努, 古崎新太郎

    膜   25 ( 1 )   23 - 31   2000年

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  • 逆ミセルの生物工学的応用

    表面   37 ( 1 )   59   1999年

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  • Extraction of DNA by reversed micelles

    Masahiro Goto, Tsutomu Ono, Akihiko Horiuchi, Shintaro Furusaki

    Journal of Chemical Engineering of Japan   32 ( 1 )   123 - 125   1999年

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    記述言語:英語   出版者・発行元:Society of Chemical Engineers, Japan  

    Deoxyribonucleotide (DNA) from salmon testes was successfully extracted by reversed micelles that are formed by a cationic surfactant in isooctane. The degree of extraction of DNA was strongly influenced by the type of surfactant in the organic solvent and ionic strength in the material aqueous phase. The driving force of the DNA transfer was electrostatic interaction between cationic surfactants and negatively charged DNA. Cationic surfactants possessing two long-alkyl chains are one of the best candidates for the successful transfer of DNA from an aqueous solution to a reversed micellar solution. Copyright © 1999 The Society of Chemical Engineers,.

    DOI: 10.1252/jcej.32.123

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  • Factors affecting protein transfer into surfactant-isooctane solution: A case study of extraction behavior of chemically modified cytochrome c

    T Ono, M Goto

    BIOTECHNOLOGY PROGRESS   14 ( 6 )   903 - 908   1998年11月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    The extraction mechanism of proteins by surfactant molecules in an organic solvent has been investigated using a chemically modified protein. We conducted guanidylation on lysine residues of cytochrome c by replacing their amino groups with homoarginine to enhance the protein-surfactant interaction. Results have shown that guanidylated cytochrome c readily forms a hydrophobic complex with dioleyl phosphoric acid (DOLPA) through hydrogen bonding between the phosphate moiety and the guanidinium groups. Although improved protein-surfactant interaction activated the formation of a hydrophobic complex at the interface, it could not improve the protein transfer in isooctane. It has been established that the protein extraction mechanism using surfactant molecules is mainly governed by two processes: formation of an interfacial complex at the oil-water interface and the subsequent solubilization of the complex into the organic phase. In addition, a kinetic study demonstrated that guanidylation of lysine accelerated the initial extraction rate of cytochrome c. This fact implies that the protein transferability from aqueous phase into organic phase depends on the protein-surfactant interaction which can be modified by protein surface engineering.

    DOI: 10.1021/bp9800844

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  • Extraction and activity of chymotrypsin using AOT-DOLPA mixed reversed micellar systems

    Masahiro Goto, Yoshio Ishikawa, Tsutomu Ono, Fumiyuki Nakashio, T. Alan Hatton

    Biotechnology Progress   14 ( 5 )   729 - 734   1998年9月

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    記述言語:英語   出版者・発行元:AIChE  

    Novel reversed micellar solutions formulated with a mixture of AOT (dioctyl sulfosuccinate) and DOLPA (dioleyl phosphoric acid) show good potential for use in reversed micellar protein extraction operations. Chymotrypsin is easily extracted from an aqueous phase into organic isooctane containing 10 mM AOT and DOLPA in a 4:1 ratio. The extraction ability of the mixed reversed micelles of 10 mM was higher than that of 200 mM AOT alone. The results of extraction indicated that the AOT-DOLPA mixed reversed micelles are very useful for separating and enriching chymotrypsin. Back-extraction of chymotrypsin from the organic phase to a fresh aqueous phase is also accomplished by adding an alcohol to the organic phase. Although the backtransfer of chymotrypsin from the reversed micelles formed by AOT alone is very slow and difficult, in the AOT-DOLPA mixed reversed micelles, the back-extraction can be achieved completely by addition of 10% (v/v) isobutyl alcohol to the reversed micellar phase. The time to attain to the equilibrium of back-extraction was reduced from more than 24 to 2 h by adding the alcohol. On the basis of the activity data, the best composition of AOT and DOLPA was a 4:1 ratio and the total surfactant concentration was 10 mM. The activity of chymotrypsin recovered from the mixed reversed micelles was higher than that of the initial protein before the forward-transfer. This result means that the novel mixed reversed micellar solutions are useful not only in separation but also in purification of proteins.

    DOI: 10.1021/bp9800790

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  • Protein refolding by reversed micelles utilizing solid-liquid extraction technique

    Y Hashimoto, T Ono, M Goto, TA Hatton

    BIOTECHNOLOGY AND BIOENGINEERING   57 ( 5 )   620 - 623   1998年3月

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    記述言語:英語   出版者・発行元:JOHN WILEY & SONS INC  

    This article reports that a reversed micellar solution is useful for refolding proteins directly from a solid source. The solubilization of denatured RNase A, which had been prepared by reprecipitation from the denaturant protein solution, into reversed micelles formulated with sodium di-2-ethylhexyl sulfosuccinate (AOT) has been investigated by a solid-liquid extraction system. This method is an alternative to the ordinary protein extraction in reversed micelles based on the liquid-liquid extraction. The solid-liquid extraction method was found to facilitate the solubilization of denatured proteins more efficiently in the reversed micellar media than the ordinary phase transfer method of liquid extraction. The refolding of denatured RNase A entrapped in reversed micelles was attained by adding a redox reagent (reduced and oxidized glutathion). Enzymatic activity of RNase A was gradually recovered with time in the reversed micelles. The denatured RNase A was completely refolded within 30 h. In addition, the efficiency of protein refolding was enhanced when reversed micelles were applied to denatured RNase A containing a higher protein concentration that, in the case of aqueous media, would lead to protein aggregation. The solid-liquid extraction technique using reversed micelles affords better scale-up advantages in the direct refolding process of insoluble protein aggregates. (C) 1998 John Wiley & Sons, Inc.

    DOI: 10.1002/(SICI)1097-0290(19980305)57:5<620::AID-BIT14>3.0.CO;2-F

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  • Catalytic properties of novel reversed micellar system on trans-esterification by α-chymotrypsin in organic media

    Ly Iskandar, Tsutomu Ono, Noriho Kamiya, Masahiro Goto, Fumiyuki Nakashio, Shintaro Furusaki

    Biochemical Engineering Journal   2 ( 1 )   29 - 33   1998年

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    記述言語:英語  

    Novel reversed micelles formulated by sodium dioleylphosphate (SDOLP) has been developed for enzymatic reaction in organic media. Comparison study between sodium bis-(2-ethylhexyl)-sulfosuccinate (Aerosol-OT or AOT) and SDOLP, which was carried out by investigating the reactivity of each reversed micellar system as reaction media for enzymatic transesterification reaction of N-acetyl-1-phenylalanine ethyl ester (APEE) and 1-propanol, leads to the upshot that α-chymotrypsin immobilized within SDOLP reversed micelles can persevere its high catalytic activity in isooctane. The initial reaction rate of the SDOLP reversed micellar system is almost 60 times higher than that in the AOT system. Additional kinetic results, including the Michaelis constant and the maximum reaction rate, reveal that the inner core of the SDOLP reversed micelles provides a better environment for enzymatic reaction than that of the conventional AOT reversed micelles. © 1998 Elsevier Science S.A. All rights reserved.

    DOI: 10.1016/S1369-703X(98)00013-8

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  • Application of reversed micelles in bioengineering

    T Ono, M Goto

    CURRENT OPINION IN COLLOID & INTERFACE SCIENCE   2 ( 4 )   397 - 401   1997年8月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:CURRENT SCIENCE LTD  

    Reverse micelles have found wider biological applications recently in terms of providing an enabling hydrophilic environment for solubilized functional biomaterials in organic media. Further, separation and purification of target proteins from aqueous solution using micellar aggregates created in hydrophobic media as well as efficient refolding of proteins in micellar solutions have become possible.

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  • Design of surfactants suitable for protein extraction by reversed micelles

    Masahiro Goto, Tsutomu Ono, Fumiyuki Nakashio, T. Alan Hatton

    Biotechnology and Bioengineering   54 ( 1 )   26 - 32   1997年4月

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    記述言語:英語   出版者・発行元:John Wiley &amp; Sons Inc  

    New surfactants have been synthesized for potential use in reversed micellar protein extraction operations. Preferential solubility of the surfactant in an aliphatic solvent such as hexane, heptane, or isooctane and the formation of reversed micelles accompanied with solubilization of significant quantities of water can be achieved by using strongly hydrophobic, twin alkyl chains as the hydrophobic moiety. Different surfactants having identical water-solubilizing capacities can have significantly different behavior in protein extractions, where extraction efficiency appears to be governed by the nature of the interfacial complex that forms between surfactants and proteins. Bulky surfactant chains provide a steric hindrance to the adsorption of the surfactant to the protein surface, thus inhibiting solvation of the protein/surfactant complex, and hence protein extraction. Under these conditions, a precipitate forms either in the bulk aqueous phase or at the interface. Surfactants that can form a close-packed complex with the protein are excellent protein-solubilizing agents. Dioleyl phosphoric acid (DOLPA) appears to be the best surfactant currently available for protein extraction.

    DOI: 10.1002/(SICI)1097-0290(19970405)54:1<26::AID-BIT3>3.0.CO;2-#

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  • Effect of organic solvents on extraction behaviour of cytochrome c using reversed micellar solutions

    Tsutomu Ono, Takayuki Miyazaki, Masahiro Goto, Fumiyuki Nakashio

    Solvent Extraction Research and Development   1996   1 - 9   1996年12月

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    The effect of organic solvents on the extraction behaviour of cytochrome c has been investigated with reversed micellar solutions. An aliphatic solvent such as hexane, octane or isooctane was suitable for protein extraction operations using the reversed micelles. Organic solvents having a different hydrophobicity show significantly different behaviour in protein extraction, where extraction efficiency appears to be governed by the nature of the interfacial complex that is formed by surfactants and proteins. Solvent effects on the protein extraction are more dominant in the AOT system rather than that in the DOLPA system. Addition of alcohol appears to decrease the activity of proteins in the back-extraction step, although it is effective for recovering proteins from the reversed micellar solutions.

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  • Extraction behavior of hemoglobin using reversed micelles by dioleyl phosphoric acid

    T Ono, M Goto, F Nakashio, TA Hatton

    BIOTECHNOLOGY PROGRESS   12 ( 6 )   793 - 800   1996年11月

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    記述言語:英語   出版者・発行元:AMER CHEMICAL SOC  

    A new surfactant, dioleyl phosphoric acid (DOLPA), has been applied to the extraction of hemoglobin using reversed micelles. The reversed micelles formed by DOLPA can easily extract hemoglobin from aqueous to reversed micellar solutions. DOLPA is the first surfactant to extract hemoglobin completely without using any cosurfactants. On the basis of the difference between DOLPA and AOT reversed micelles in the forward extraction behavior of hemoglobin, the nature of the interfacial complex that would be formed between surfactants and hemoglobin at the oil-water interface was found to be the dominant factor in determining the extraction efficiency of hemoglobin by reversed micelles. In addition, back-transfer studies of hemoglobin from the DOLPA reversed micelles were also carried out by the phase transfer method. It was found that hemoglobin, once dissolved into the DOLPA reversed micelles, is not transferred to a fresh aqueous solution even when the conditions are adjusted to not allow the forward transfer of hemoglobin. However, the addition of several kinds of alcohol drastically improved the yield in the back-transfer of hemoglobin. The efficiency in the back-transfer of hemoglobin strongly depends on the aqueous conditions that are in contact with the reversed micelles, such as pH, ionic strength, and alcohol concentration. A pH higher than the pi of hemoglobin, a salt concentration lower than that of the water pool, and the proper concentration of alcohol are required for the recovery aqueous phase to ensure the back-transfer of hemoglobin from the DOLPA reversed micelles.

    DOI: 10.1021/bp960055y

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  • Novel immobilized enzymes utilizing reversed micellar solutions as an optical resolution tool

    T Ono, M Goto, F Nakashio, TA Hatton

    JOURNAL OF CHEMICAL ENGINEERING OF JAPAN   29 ( 4 )   695 - 697   1996年8月

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    記述言語:英語   出版者・発行元:SOC CHEMICAL ENG JAPAN  

    DOI: 10.1252/jcej.29.695

    Web of Science

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  • Reversed micelles recognize an active protein

    Masahiro Goto, Tsutomu Ono, Fumiyuki Nakashio, T. Alan Hatton

    Biotechnology Techniques   10 ( 3 )   141 - 144   1996年

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    記述言語:英語   出版者・発行元:Springer Netherlands  

    The extraction behavior of native and heated-denatured α-chymotrypsin has been investigated with two different reversed micellar systems. A large difference in the degree of extraction was observed for the native relative to the denatured α-chymotrypsin. In particular, mixed reversed micelles formulated with DOLPA (dioleyl phosphoric acid) and AOT show a high selectivity for the active α-chymotrypsin.

    DOI: 10.1007/BF00158935

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  • Protein Extraction by New Reversed Micelles with Di(Tridecyl) Phosphoric Acid

    Masahiro Goto, Motohiro Kuroki, Tsutomu Ono, Fumiy uki Nakashio

    Separation Science and Technology   30 ( 1 )   89 - 99   1995年

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    記述言語:英語  

    Di(tridecyl) phosphoric acid (DTDPA) was synthesized as a new surfactant for protein extraction by reversed micelles. DTDPA can form stable reversed micelles in the concentration range above 1 mM. The size of the DTDPA reversed micelles was smaller than that of conventional AOT (sodium-di-2-ethylhexyl sulfosucci-nate) reversed micelles under the same conditions. The formation of reversed micelles using DTDPA can be controlled by adjusting the aqueous pH. The extraction behavior of some proteins from an aqueous phase into the reversed micellar phase of DTDPA has been investigated by varying the experimental conditions (pH, ionic strength, surfactant concentration). It was found that reversed micelles with DTDPA can extract many proteins. In particular, hemoglobin, which is difficult to extract with an AOT reversed micelle, can be extracted in the DTDPA reversed micelles. In the new reversed micellar system, phase separation was very fast even at a high concentration of DTDPA. © 1995, Taylor &amp
    Francis Group, LLC. All rights reserved.

    DOI: 10.1080/01496399508012215

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  • Protein extraction and extraction mechanism by reversed micelles

    32 ( 9 )   601   1994年

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▼全件表示

講演・口頭発表等

  • Microchannel wet-spinning to prepare high tensile nanofibers 招待

    T. Ono, N. Seike, T. Onji, S. Masumoto, T. Watanabe

    35th Advanced Materials Congress, Sweden  2020年10月27日 

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    開催年月日: 2020年10月27日 - 2020年10月29日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Emulsion polymerization in a microfluidic device 招待

    Tsutomu Ono

    The 5th Asian Symposium on Emulsion Polymerization and Functional Polymeric Microspheres (ASEPFPM 2015)  2015年10月26日 

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    開催年月日: 2015年10月24日 - 2015年10月26日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • 湿式紡糸で創る微細な機能性繊維 〜製造技術としての課題と可能性〜 招待

    小野努

    ナノファイバー研究会(第31回)研究例会  2020年9月11日 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • マイクロ流路を利用した機能性ナノ繊維の製造技術 招待

    小野努

    マイクロ化学プロセス第10回講演会  2018年11月26日 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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産業財産権

  • 湿式紡糸繊維,湿式成膜フィルムおよびそれらの製造方法

    小野努, 渡邉貴一

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    出願人:岡山大学

    出願番号:特願PCT/JP/2019/038576  出願日:2019年9月30日

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  • イオン液体モノマー,高分子およびその製造方法並びに架橋高分子

    小野努, 渡邉貴一

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    出願人:岡山大学

    出願番号:特願2019-164247  出願日:2019年9月10日

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  • セルロースナノファイバーの製造方法

    小野努,ムハマッド モニルッザマン

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    出願人:岡山大学

    出願番号:特願2013-131448  出願日:2013年6月24日

    公開番号:特開2015-004151  公開日:2015年1月8日

    特許番号/登録番号:特許第6229927号  登録日:2017年10月27日  発行日:2017年11月15日

    権利者:岡山大学

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  • 基材と結合可能なイオン液体を含有する被覆剤、それから得られる被覆層および被覆基材、ならびにそれを用いた被覆方法

    小野努, 福田剛大

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    出願人:岡山大学

    出願番号:特願2013-027639  出願日:2013年2月15日

    公開番号:特開2014-156529  公開日:2014年8月28日

    特許番号/登録番号:特許第6218133号  登録日:2017年10月6日  発行日:2017年10月25日

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  • 生分解性と生体親和性に優れたナノ繊維の製造方法

    小野努, 木村幸敬

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    出願人:岡山大学

    出願番号:特願2012-531863  出願日:2011年8月29日

    公開番号:特開PCT/JP2011/069439, WO2012/029710 

    特許番号/登録番号:特許第5835743号  登録日:2015年11月13日  発行日:2015年12月24日

    権利者:岡山大学

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  • 生分解性中空微粒子およびその製造方法

    小野努, 木村幸敬, 村中誠

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    出願人:岡山大学

    出願番号:特願2010-147437  出願日:2010年6月29日

    公開番号:特開2012-011268  公開日:2012年1月19日

    特許番号/登録番号:特許第5780507号  登録日:2015年7月24日 

    権利者:岡山大学

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  • ヒドロゲルカプセルの製造方法

    小野努, 木村幸敬, 安川政宏

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    出願人:岡山大学

    出願番号:特願2010-147438  出願日:2010年6月29日

    公開番号:特開2012-011269 

    特許番号/登録番号:特許第5858451号  登録日:2015年12月25日  発行日:2016年2月10日

    権利者:岡山大学

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▼全件表示

受賞

  • 化学工学会奨励賞

    2002年  

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    受賞国:日本国

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  • Encouragement Awards of Japan Chemical Engineering Society

    2002年  

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  • 化学工学会九州支部学生賞

    1996年  

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    受賞国:日本国

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共同研究・競争的資金等の研究

  • モノフィラメント状微細繊維加工による機能性繊維製品の開発

    2021年10月 - 2022年03月

    国立研究開発法人新エネルギー・産業技術総合開発機構(NEDO)  研究開発型スタートアップ支援事業 

    小野努

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    担当区分:研究代表者 

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  • チャネル型正浸透膜の創製と究極的ゼロエネルギー水処理プロセスの構築

    研究課題/領域番号:18H03854  2018年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業 基盤研究(A)  基盤研究(A)

    松山 秀人, 彌田 智一, 松方 正彦, 小野 努, 吉岡 朋久, 中川 敬三, 神尾 英治, 佐伯 大輔, 高橋 智輝, 稲田 飛鳥

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    担当区分:研究分担者 

    配分額:43940000円 ( 直接経費:33800000円 、 間接経費:10140000円 )

    1.新規水チャネル型FO膜の創製
    1-1.環状ペプチド分子集合体チャネル膜の創製(松山、吉岡、佐伯)では、分子動力学計算を用いて環状ペプチドチャネル分子を設計、合成し、これをリン脂質二分子膜に導入することで新規生体模倣型FOチャネル膜の開発を行った。1-2.高分子液晶垂直配向チャネル膜の創製(彌田、佐伯、稲田)では、高分子液晶の垂直配向シリンダー構造を水チャネルとして利用したFO膜の創製を行った。各種支持膜との複合化製膜プロセスを構築した。1-3.革新的ロバスト無機ゼオライトFO膜の創製(松方)では、ZSM-5等のゼオライトが持つ親水性ミクロ細孔特性を利用して、安定性が高く高温にも耐える全く新しい無機FO膜の開発を行った。1-4.計算機科学による高機能FO膜開発支援 (吉岡)では、分子動力学計算により水チャネルの正浸透透水モデルを構築し、高透水性発現に必要な構造や物性をシミュレーションにより解明するとともに、結果のフィードバックにより、高透水性FO膜開発支援を行った。
    2.新規刺激応答性駆動溶液(DS)の創製(小野、高橋)
    熱応答性イオン液体DSの創製を目指し100種類以上のイオン液体分子について量子化学計算を活用して系統的なスクリーニングを行い、化学構造と温度相転移特性との関係性を明らかにするとともに、熱応答性イオン液体の温度依存的浸透圧発現機構を解析し、高浸透圧と相分離特性を両立する高性能なイオン液体DSの創出を行った。
    3.FO膜透過とDS再生を含む連続システムによるFS評価とFO膜システムの実証(松山、神尾、中川)
    FO膜とDSを用いた連続FOシステムの構築を行い、構築したシステムにより、熱応答性イオン液体DSの性能確認を行うとともに、海水淡水化を想定したFO膜プロセスで連続的にモデル海水から純水を得ることに成功した。

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  • マイクロ空間における迅速な相転移誘起の制御と微細構造設計

    研究課題/領域番号:18H01767  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    小野 努

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    担当区分:研究代表者 

    配分額:17680000円 ( 直接経費:13600000円 、 間接経費:4080000円 )

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  • マイクロ湿式紡糸技術をコアとした高付加価値材料の精密生産

    2017年 - 2019年

    科学技術振興機構  大学発新産業創出プログラム(START) 

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    担当区分:研究代表者 

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  • セグメント空間内相転移における核生成および流体特性制御による精密材料設計(国際共同研究強化)

    研究課題/領域番号:16KK0131  2017年 - 2019年

    日本学術振興会  科学研究費助成事業 国際共同研究加速基金(国際共同研究強化)  国際共同研究加速基金(国際共同研究強化)

    小野 努

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    担当区分:研究代表者 

    配分額:15080000円 ( 直接経費:11600000円 、 間接経費:3480000円 )

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  • 超高機能構造タンパク質による素材産業革命

    2017年 - 2018年

    内閣府(CAO)  革新的研究開発推進プログラム(ImPACT) 

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    担当区分:研究分担者 

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  • ソフト界面への金属集積を指向する界面設計技術の構築

    研究課題/領域番号:16K14459  2016年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    小野 努, 渡邉 貴一, 恒吉 俊彦, 今井 慶彦, 輿羽瀬 佑

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    担当区分:研究代表者 

    配分額:3640000円 ( 直接経費:2800000円 、 間接経費:840000円 )

    材料表面の機能化は,国内外に向けて高付加価値材料を創出していくうえで極めて重要な課題であるが,材料の成形加工とともに表面に金属を配向させる手法はほとんどない。本研究では,金属錯体を連結部に有するメタロ超分子界面活性剤を用いて材料表面に金属錯体部を集積させることを試みた。本手法で一定の金属錯体を固体表面へ配向させることはできたが,更なる金属特性を固体表面に導入すべく,ナノ粒子の液液界面への配向とそれを触媒とした無電解めっき反応による界面における金属薄膜形成を実現した。

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  • マイクロ湿式紡糸プロセスによるPVA繊維の改質

    2016年

    科学技術振興機構  地域産学バリュープログラム(A-STEP機能検証フェーズ) 

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    担当区分:研究代表者 

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  • セグメント空間内相転移における核生成制御手法の構築

    研究課題/領域番号:26289291  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    小野 努, 渡邉 貴一

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    担当区分:研究代表者 

    配分額:16120000円 ( 直接経費:12400000円 、 間接経費:3720000円 )

    液滴やスラグ流といった非相溶流体によって形成されるセグメント空間内における核生成挙動を様々な観点から検証し,液滴内晶析反応からは核生成頻度の解析によって,核生成速度の算出を可能にし,簡便な核生成速度計測手法として構築することができた。また,マイクロ空間内における乳化重合反応からは,核生成の精密制御と物質移動促進によって,回分反応とは異なる高分子重合挙動を見出した。いずれの研究成果も,核生成挙動を制御するためにセグメント空間が非常に効果的であることを示唆するものであり,今後の製造技術革新や精密な材料設計に有用な知見が得られた。

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  • 界面分子制御による無電解めっき反応を利用したメタルカプセルの調製

    研究課題/領域番号:25630344  2013年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    小野 努

      詳細を見る

    担当区分:研究代表者 

    配分額:4030000円 ( 直接経費:3100000円 、 間接経費:930000円 )

    本研究ではマイクロカプセルの更なる機能化を探求する目的で,「無電解めっき反応」に着目し,マイクロカプセル上への金属結合された層の構築を目指した。実験結果から,表面における金属触媒の担持が極めて重要であることが分かり,当初の目標であった液液界面や気液界面への直接金属膜の導入は実現できなかったが,今後の開発の可能性を示唆できた。一方で,pH制御によって無電解めっき反応によるマイクロカプセルへの磁気特性の付与を実現できた。

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  • 界面エネルギーを高次制御した新規ナノ乳化法の開発

    2012年

    科学技術振興機構  研究成果最適展開支援プログラム(A-STEP) 

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    担当区分:研究代表者 

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  • 革新的マイクロ湿式紡糸プロセスによる高機能ナノファイバーの創製

    2011年 - 2014年

    新エネルギー・産業技術総合開発機構(NEDO)  先導的産業技術創出事業(若手研究グラント) 

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    担当区分:研究代表者 

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  • 多層ヒドロゲルの精密生産技術を活用した機能性ヒドロゲルカプセル創製

    2011年

    科学技術振興機構  研究成果最適展開支援プログラム(A-STEP) 

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    担当区分:研究代表者 

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  • 界面制御ラジカル重合による機能性微粒子の創製

    2009年

    科学技術振興機構  地域イノベーション創出総合支援事業 重点地域研究開発推進プログラム シーズ発掘試験 

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    担当区分:研究代表者 

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  • 光線力学的治療に有効な多機能型薬剤内封ナノ運搬体の開発

    2007年 - 2009年

    厚生労働省  校正労働科学研究費補助金 医療機器開発推進研究(ナノメディシン研究) 

    大河原賢一

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    担当区分:研究代表者 

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  • ピコリットルバイオリアクターのオンデマンド調製技術の確立

    研究課題/領域番号:19760552  2007年 - 2008年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    小野 努

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    担当区分:研究代表者 

    配分額:3570000円 ( 直接経費:3300000円 、 間接経費:270000円 )

    ピコリットルスケールの体積を有するマイクロカプセルを利用してバイオリアクターへの応用を検討するもために,精密な微細液滴調製技術の構築と細胞と同等レベルの単分散マイクロカプセル内での物質生産の構築を行ってきた。マイクロリアクターを用いて単分散ピコリットルカプセルの調製を実現し,そのなかで大腸菌の培養と増殖およびプラスミド(目的蛋白質の遺伝子をコードした環状DNA)の導入によって目的蛋白質の生産を確認することができた。

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  • 熱誘起分子シンクロナイゼーションによる生分解性ナノカプセルの創製

    研究課題/領域番号:17360383  2005年 - 2007年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    吉澤 秀和, 小野 努, 北村 吉朗

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    担当区分:連携研究者 

    配分額:16490000円 ( 直接経費:15500000円 、 間接経費:990000円 )

    本研究では、水溶性生分解性高分子であるポリアスパラギン酸誘導体に温度応答機能を重畳した新規な高分子を種々合成し、その機能の熱誘起分子シンクロナイゼーションを利用した生体分子を内包する新規な生分解性ナノカプセルの創製を目的としている。
    そこで、当該年度では、前年度合成し成功し、その感温特性が確認された水溶性感温性ポリアスパラギン酸誘導体(Thermo-PAspD)について、熱誘起相転移によって形成するナノスフェアの生成メカニズムの解明と生成したナノスフェアの粒径制御法について検討した。
    まず、ナノスフェア形成に及ぼすプロセス因子の影響として、まず、側鎖構造としてイソプロピル基を導入したIPA-PSIを用いて、ナノスフェア形成に及ぼす昇温速度の影響を検討した。その結果、IPA-PSIナノスフェアの粒径は、冷却速度や洗浄攪拌速度などに影響を受けず、高濃度において生起するナノスフェアの粒径はほぼ一定となった。また、加熱温度及び加熱時間が最も粒径に影響を与えることが明らかになった。これらの結果から、脱水和したIPA-PSIの供給が充分な条件において、IPA-PSIナノスフェアの粒径は、溶解しているIPA-PSIの量ではなく調製温度と曇点との差に大きく依存することが示唆され、平均粒径を120〜190nmの範囲で制御できた。
    さらに、ナノスフェア形成に及ぼす材料因子について検討した結果、IPA-PSIのLCSTは、イソプロピル基の導入率の上昇に伴って減少し、分子量の増加に伴って増加する傾向が見られた。電解質の添加効果に関しては非常に複雑に影響しており、IPA-PSIのLCSTは特殊な依存性が観察された。

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  • ペプチドタグを利用した総括的タンパク質リフォールディングプロセスの構築

    研究課題/領域番号:17760626  2005年 - 2006年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    小野 努

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    担当区分:研究代表者 

    配分額:3400000円 ( 直接経費:3400000円 )

    本研究では,総括的なタンパク質リフォールディング効率の向上を目指して,ペプチドタグを導入したタンパク質の生産とナノスフェアを利用した選択的凝集による高効率リフォールディング手法の構築を目指して行った。まず,N末端およびC末端の両方にNiとの錯形成が可能な6つのヒスチジン残基が並んだペプチド配列(以下,His-tag)を遺伝子的に導入したタンパク質発現ベクターを調製した。特に,両端へHis-tagを導入した緑色蛍光タンパク質(2x His-tag GFP)を調製して,ペプチドタグの影響を受けることなく大腸菌を利用して安定にタンパク質を生産できることを確かめた。
    また,凝集挙動を色によって識別できる可能性を有するため,ナノスフェアとして金コロイドを選定し,Ni配位子を導入しても安定な金コロイド調製手法を確立するために,高分子で分散安定した金コロイドの調製を試みた。生分解性も期待できるポリアスパラギン酸を主鎖として側鎖に金コロイドの安定な分散に寄与する官能基とHis-tag認識部位を導入することで2x His-tagタンパク質の高効率リフォールディングに有用なナノスフェアの調製を行った。数十nmの単分散な金コロイドを調製できるポリアスパラギン酸系高分子の設計が可能になったが,十分量のHis-tag認識部位をナノスフェア表面に導入するには至っておらず,更なる高分子の精密設計が必要であることがわかった。
    これらの知見から,His-tag認識部位をナノスフェア表面に効率的に呈示するための改善を施すことによって,変性溶液中からの2x His-tag GFPの選択的凝集とリフォールディングが可能になるものと期待される。本研究成果を基にして更なるナノスフェア表面を精密設計することで,コロイド化学をタンパク質工学に融合させた新しいリフォールディングツールの構築が期待できる。

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  • 酵素包括ゾル-ゲルシリカモノリスマイクロチャネルバイオリアクターの開発

    研究課題/領域番号:15656212  2003年 - 2004年

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    川上 幸衛, 境 慎司, 小野 努

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    担当区分:連携研究者 

    配分額:2900000円 ( 直接経費:2900000円 )

    内径数mmのPEEKチューブやガラス毛細管,内径数百μmのPEEKSTLチューブの内部に,テトラメトキシシランとメチルトリメトキシシランの1:4混合物を前駆体としたゾル-ゲル法により,プロテアーゼもしくはリパーゼを包括した有機-無機ハイブリッドシリカモノリスをその場形成させた.モノリスは直径数μmの微粒子の集合体からなり85%程度の空隙を有する.この空隙を基質溶液の流路とする固定化酵素マイクロバイオリアクターを構築した.
    まず,乾燥に伴うシリカの収縮を最小限にするために,種々のゾル-ゲル反射条件,ならびにPFGやPVAなどの添加剤の効果を検討した.その結果,酵素サンプルに当初から安定化剤として添加されているデキストリンをさらに追加添加し,最終量を最適化することによって収縮が防止できることを見出した.
    つぎに,有機溶媒中におけるプロテアーゼによるグリシドールと酪酸ビニルのエステル交換およびリパーゼによるグリシドールと酪酸からのエステル合成をモデル反応に,同じ固定化酵素ゲル粒子の懸濁回分反応器との比較において,流通マイクロバイオリアクターの性能を検討した.その結果,一定の時間因子においては,マイクロバイオリアクターの反応率は単なる回分反応器の反応率を上回ることが分かったが,マイクロバイオリアクター内の酵素反応速度は基質の液固間物質移動過程によって影響を受けていることが明らかとなった.この効果を回分反応器とマイクロバイオリアクターにおける酵素反応速度の単純なモデル解析によって定量的に表し,マイクロバイオリアクターの性能方程式を決定した.
    さらに,リアクターの高性能化のために,テトラメトキシシランとジメチルジメトキシシランの混合物を原料とした気相もしくは超臨界相ゾル-ゲル反応によって酵素のシリカ被覆を行い,一層の活性向上がもたらされることを見いだした.

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  • ナノ分子集合組織を利用した非水系膜型バイオリアクターの開発

    研究課題/領域番号:14750607  2002年 - 2003年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    小野 努

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    担当区分:研究代表者 

    配分額:3500000円 ( 直接経費:3500000円 )

    ナノ分子集合組織である逆ミセル溶液を限外濾過することによって、高効率な蛋白質リフォールディングが可能なことをこれまでに示してきたが、本年度は膜型反応器という特性を活かして、連続的なリフォールディング操作を行うことのできる蛋白質リフォールディングリアクターの開発について得た成果を以下に述べる。
    限外濾過膜を介して、分画分子量以下の低分子化合物である変性剤(本研究では尿素)や酸化還元試薬(本研究では酸化型/還元型グルタチオンあるいはシスチン/システイン)が膜内外の逆ミセル溶液間で物質移動を起こす。このときの変性剤濃度の減少速度が蛋白質のリフォールディング速度にも反映されるため、実際の変性剤濃度減少速度と蛋白質のリフォールディング挙動を測定して変性剤を効率よく除去可能な膜型反応器を設計した。
    一般的な透析装置(回分操作)、膜内外の逆ミセル溶液を循環させた閉鎖循環型装置、さらに中空糸モジュールを用いた中空糸膜型装置をそれぞれ作製し、酸化還元試薬組成がリフォールディング効率に与える影響については回分操作によって検討した。その結果、酸化剤の比率増加にともないリフォールディング効率が向上した。このように、瞬間的にリフォールディング反応が進行してしまう水溶液中と比較して反応が極めて遅いため、蛋白質の高次構造形成過程の観察に非常に有効な系であることがわかった。
    また、実際にリフォールディングが困難とされる蛋白質のインクルージョンボディを用いて本手法の回分装置を利用することで蛋白質のリフォールディングを試みた。水に不溶な蛋白質凝集体であったが、本手法によるリフォールディング操作により一部の蛋白質が水に可溶な状態で回収できた。しかしながら、回収率としては依然低いため、今後の実験条件の最適化が必要とされる。

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  • クロロエチレン類の好気的微生物分解のための高効率バイオリアクターシステムの開発

    研究課題/領域番号:11555222  1999年 - 2001年

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    川上 幸衛, 井嶋 博之, 陶山 明子, 古川 謙介, 小野 努

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    担当区分:連携研究者 

    配分額:13100000円 ( 直接経費:13100000円 )

    アガロースゲルに包括した組み換えPseudomonas putida KF715-P6株によるTCE分解に適した高効率バイオリアクターシステムを開発する目的で,菌体の活性と安定性を高く維持し得る分解条件並びに賦活条件の最適化を行った.得られた結果を以下に列挙する.
    分解温度としては,分解活性の至適温度は30℃であったが,その場合より高い安定性を与える15℃に設定した.最適な賦活条件は,pH6.5,温度4℃において,0.2mMグルコース及び5mMギ酸を含む無機塩培地(BSM)中において6時間振盪することであった.この条件下における菌体の賦活によって,残存活性は、30℃における賦活なしの場合と比較すると、約30%から60%へとほぼ倍増した.
    分解培地として水の代わりに上記の最適化されたBSMGを使用することによって,分解活性及び残存活性は,それぞれ,50%及び10%増加した.また,振盪速度や集菌までの培養時間などの培養条件が,その後のTCE分解に対する菌体の性能に大きな影響を及ぼすことが明かとなった.つまり,生菌密度,TCE分解初期活性,残存活性並びに分解容量は,振盪速度80rpmで培養し,菌体同収の増殖のフェーズが対数増殖期である菌体が最も高い値を示した.しかし、対数増殖期の菌体量は静止期の約80%のため,最適な菌体回収の増殖のフェーズは静止期とした.この条件下で分解培地を精製水からBSMGにし,さらに賦活を18時間行うと約90%の残存活性を示した.
    これらの実験結果に基づいて,疎水性のホローファイバー膜モジュールによるTCEの分離と上記の最適培地中でアガロースミクロゲルビーズ包括菌体によるTCE分解を組み合わせたバイオリアクターシステムを提案した.

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  • 有機媒体中における分子集合体を利用した高度分子認識

    研究課題/領域番号:97J00392  1998年

    日本学術振興会  科学研究費助成事業 特別研究員奨励費  特別研究員奨励費

    小野 努

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    担当区分:研究代表者 

    配分額:900000円 ( 直接経費:900000円 )

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担当授業科目

  • 化学・生命系入門 (2021年度) 第1学期  - 金1~2

  • 化学工学2A (2021年度) 第1学期  - 火1,火2

  • 化学工学2B (2021年度) 第2学期  - 火1,火2

  • 化学工学2 (2021年度) 1・2学期  - 火1,火2

  • 実践応用化学 (2021年度) 前期  - その他

  • 応用化学ゼミナール1 (2021年度) 前期  - その他

  • 応用化学ゼミナール2 (2021年度) 後期  - その他

  • 応用化学基礎 (2021年度) 後期  - 月3~4,火3~4

  • 応用化学特別研究 (2021年度) 通年  - その他

  • 有機遷移金属化学 (2021年度) 後期  - 水1~2

  • 材料プロセス各論4 (2021年度) 夏季集中  - その他

  • 材料プロセス工学2 (2021年度) 前期  - 月3~4

  • 材料機能化学特論4 (2021年度) 集中  - その他

  • 機能界面設計学 (2021年度) 後期  - その他

  • 物理化学3 (2021年度) 第4学期  - 水3,水4,金5,金6

  • 界面プロセス工学演習 (2021年度) 通年  - その他

  • 化学基礎 (2020年度) 第2学期  - 水1,水2,金1,金2

  • 化学基礎 (2020年度) 第2学期  - 水1,水2,金1,金2

  • 化学工学2A (2020年度) 第1学期  - 火1,火2

  • 化学工学2B (2020年度) 第2学期  - 火1,火2

  • 化学工学2 (2020年度) 1・2学期  - 火1,火2

  • 合成化学各論4 (2020年度) 夏季集中  - その他

  • 合成化学各論2 (2020年度) 夏季集中  - その他

  • 合成化学各論4 (2020年度) 夏季集中  - その他

  • 合成化学各論6 (2020年度) 夏季集中  - その他

  • 実践応用化学 (2020年度) 前期  - その他

  • 応用化学ゼミナール1 (2020年度) 前期  - その他

  • 応用化学ゼミナール2 (2020年度) 後期  - その他

  • 応用化学基礎 (2020年度) 後期  - 月3~4,火3~4

  • 応用化学特別研究 (2020年度) 通年  - その他

  • 材料プロセス工学1 (2020年度) 前期  - 月3,月4

  • 材料機能化学特論8 (2020年度) 夏季集中  - その他

  • 機能界面設計学 (2020年度) 特別  - その他

  • 物理化学3 (2020年度) 第4学期  - 水3,水4,金5,金6

  • 物質合成化学特論8 (2020年度) 夏季集中  - その他

  • 界面プロセス工学演習 (2020年度) 通年  - その他

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社会貢献活動

  • マイクロ流路が最先端の化学工場になる

    役割:出演, 講師

    フロムページ  夢ナビライブ  2018年6月16日

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    種別:インターネット

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メディア報道

  • 自己多層乳化を用いたマトリョーシカ微粒子の調製〜油と水を混ぜてすぐ固めるだけ〜 インターネットメディア

    岡山大学  岡山大学  https://www.okayama-u.ac.jp/tp/release/release_id908.html  2021年12月

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    執筆者:本人以外 

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学術貢献活動

  • 第20回高分子ミクロスフェア討論会

    役割:企画立案・運営等, パネル司会・セッションチェア等

    実行委員長  2018年11月14日 - 2018年11月16日

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    種別:学会・研究会等 

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