Nagase, Kenichi



Faculty of Pharmacy, Department of Pharmaceutical Sciences 創薬物理化学講座 (Shiba-Kyoritsu)


Associate Professor

Profile Summary 【 Display / hide

Career 【 Display / hide

  • 2005.04

    Tokyo Women's Medical University, Institute of Advanced Biomedical Engineering and Science, Postdoctoral Research Fellow

  • 2007.04

    Tokyo Women's Medical University, Institute of Advanced Biomedical Engineering and Science, Assistant Professor

  • 2011.04

    Tokyo Women's Medical University, Institute of Advanced Biomedical Engineering and Science, Lecturer

Academic Background 【 Display / hide

  • 1996.04

    Waseda University, School of Science and Engineering, Department of Chemical Engineering

    Japan, University, Graduated

  • 2000.04

    Waseda University, Graduate School of Science and Engineering, Department of Chemical Engineering

    Japan, Graduate School, Completed, Master's course

  • 2002.04

    Waseda University, Graduate School of Science and Engineering, Department of Chemical Engineering

    Japan, Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(工学), Waseda University, Coursework, 2005.03

Licenses and Qualifications 【 Display / hide

  • 日本分析化学会 液体クロマトグラフィー分析士 初段, 2017.09


Books 【 Display / hide

  • 生体内移動論

    長瀬 健一, 朝倉書店, 2021.08

    Scope: 第8章 薬物移動論,  Contact page: 362-408

  • Stimuli-Responsive Polymers Handbook

    Kenichi Nagase, Hideko Kanazawa, 株式会社エヌ・ティー・エス, 2018.12

    Scope: 温度応答性クロマトグラフィー

  • Temperature‐responsive Polymers for Tissue Engineering

    Kenichi Nagase, Masayuki Yamato, Teruo Okano, John Wiley & Sons, 2018.06

    Scope: Temperature‐Responsive Polymers: Chemistry, Properties and Applications

  • Polymer and Biopolymer Brushes: For Materials Science and Biotechnology

    Kenichi Nagase, Teruo Okano, John Wiley & Sons, 2018.01

    Scope: Thermoresponsive Polymer Brushes for Thermally Modulated Cell Adhesion and Detachment

  • バイオマテリアル-その基礎と先端研究への応用

    Kenichi Nagase、Masayuki Yamato, 東京化学同人, 2016.02

    Scope: 細胞シート

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Papers 【 Display / hide

  • Temperature-responsive spin column for sample preparation using an all-aqueous eluent

    Nagase, Kenichi, Ishizawa, Yuta, Inoue, Masakazu, Kokubun, Matsurika, Yamada, Sota and Kanazawa, Hideko

    Analytica Chimica Acta 1179   338806 2021.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0003-2670

     View Summary

    We present a temperature-responsive spin column using an all-aqueous eluent. The method is intended as a simple sample preparation method for protein removal from serum, which is required for serum drug analysis. As packing materials for the spin column, we prepared two types of silica beads via surface-initiated radical polymerization. The large beads (diameter, 40–63 μm) were grafted with a temperature-responsive cationic copolymer, poly(N-isopropylacrylamide-co-N,N-dimethylaminopropyl acrylamide-co-n-butyl methacrylate) (P(NIPAAm-co-DMAPAAm-co-BMA)), and the small beads (diameter, 5 μm) were grafted with a temperature-responsive hydrophobic copolymer, P(NIPAAm-co-BMA). The beads were packed into the spin column as a double layer: P(NIPAAm-co-BMA) silica beads on the bottom and P(NIPAAm-co-DMAPAAm-co-BMA) silica beads on the top. The sample purification efficacy of the prepared spin column was evaluated on a model sample analyte (the antifungal drug voriconazole mixed with blood serum proteins). At 40 °C, the serum proteins and voriconazole were adsorbed on the prepared spin column via hydrophobic and electrostatic interactions. When the temperature was decreased to 4 °C, the adsorbed voriconazole was eluted from the column with the pure water eluent, while the serum proteins remained in the column. This temperature-responsive spin column realizes sample preparation simply by changing the temperature.

  • Anion species-triggered antibody separation system utilizing a thermo-responsive polymer column under optimized constant temperature

    Nomoto, Daiki, Nagase, Kenichi, Nakamura, Yubuki, Kanazawa, Hideko, Citterio, Daniel and Hiruta, Yuki

    Colloids and Surfaces B: Biointerfaces 205   111890 2021.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  0927-7765

     View Summary

    Although the field of antibody drugs has grown larger, the antibody production still faces several challenges. Effective antibody purification is required, but the conventional purification method for antibodies is cost intensive and often causes aggregation problems, indicating the need for new alternative antibody purification methods. In the present study, a constant temperature antibody purification system for use with a thermo-responsive polymer column was developed based on switching of anion species in eluents. By adjusting the temperature for each antibody, the developed column enabled separation of the therapeutic monoclonal antibodies, rituximab and trastuzumab, from contaminants without changing salt concentration or pH of the eluents. The thermo-responsive hydrogel-modified column packing material was synthesized by introducing n-butyl methacrylate, acrylic acid, N,N′-methylenebisacrylamide and N-isopropylacrylamide to the surface of silica beads with an initiator by a graft-from approach. Elution behavior of antibodies with three types of anions, such as citrate, phosphate, and chloride were tested under three different temperature conditions. It was demonstrated that the thermo-responsive hydrogel grafted column showed a switchable antibody retention behavior at constant temperature and salt concentration, with antibody adsorption by NaCl eluent and desorption by citric acid buffer eluent.

  • Thermoresponsive interfaces obtained using poly(N-isopropylacrylamide)-based copolymer for bioseparation and tissue engineering applications

    Nagase, Kenichi

    Advances in Colloid and Interface Science 295   102487 2021.09

    Research paper (scientific journal), Single Work, Accepted,  ISSN  0001-8686

     View Summary

    Poly(N-isopropylacrylamide) (PNIPAAm) is the most well-known and widely used stimuli-responsive polymer in the biomedical field owing to its ability to undergo temperature-dependent hydration and dehydration with temperature variations, causing hydrophilic and hydrophobic alterations. This temperature-dependent property of PNIPAAm provides functionality to interfaces containing PNIPAAm. Notably, the hydrophilic and hydrophobic alterations caused by the change in the temperature-responsive property of PNIPAAm-modified interfaces induce temperature-modulated interactions with biomolecules, proteins, and cells. This intrinsic property of PNIPAAm can be effectively used in various biomedical applications, particularly in bioseparation and tissue engineering applications, owing to the functionality of PNIPAAm-modified interfaces based on the temperature modulation of the interaction between PNIPAAm-modified interfaces and biomolecules and cells. This review focuses on PNIPAAm-modified interfaces in terms of preparation method, properties, and their applications. Advances in PNIPAAm-modified interfaces for existing and developing applications are also summarized.

  • Effect of pore diameter on the elution behavior of analytes from thermoresponsive polymer grafted beads packed columns

    Nagase, Kenichi, Umemoto, Yuta, Kanazawa, Hideko

    Scientific Reports 11 ( 1 ) 9976 2021.05

    Research paper (scientific journal), Joint Work, Accepted

     View Summary

    Temperature-responsive chromatography using thermoresponsive polymers is innovative and can control analyte retention via column temperature. Analyte elution behavior in this type of chromatography depends on the modified thermoresponsive polymer and the structure of the base materials. In the present study, we examine the effect of the pore diameter of silica beads on analyte elution behavior in temperature-responsive chromatography. Poly(N-isopropylacrylamide-co-n-butyl methacrylate) hydrogel was applied to beads of various pore sizes: 7, 12, and 30 nm. Almost the same amount of copolymer hydrogel was applied to all beads, indicating that the efficiency of copolymer modification was independent of pore size. Analyte retention on prepared beads in a packed column was observed using steroids, benzodiazepines, and barbiturates as analytes. Analyte retention times increased with temperature on packed columns of 12- and 30-nm beads, whereas the column packed with 7-nm beads exhibited decreased retention times with increasing temperature. The difference in analyte elution behavior among the various pore sizes was attributed to analyte diffusion into the bead pores. These results demonstrate that bead pore diameter determines temperature-dependent elution behavior.

  • Autonomous Nanoscale Chemomechanical Oscillation on the Self-Oscillating Polymer Brush Surface by Precise Control of Graft Density

    Homma, Kenta, Ohta, Yuji, Minami, Kosuke, Yoshikawa, Genki, Nagase, Kenichi, Akimoto, Aya M. and Yoshida, Ryo

    Langmuir 37 ( 14 ) 4380 - 4386 2021.04

    Research paper (scientific journal), Accepted,  ISSN  0743-7463

     View Summary

    As a novel functional surface, a self-oscillating polymer brush that undergoes autonomous, periodic swelling/deswelling during the Belousov–Zhabotinsky (BZ) reaction has been developed. Although extensive research has revealed how the fundamental aspects of the BZ reaction can be regulated based on the surface design of the self-oscillating polymer brush, design strategies for the induction of mechanical oscillation remain unexplored. Herein, we investigated the graft density effects on the phase transition behavior, which is an important design parameter for the mechanical oscillation of the modified polymer. The self-oscillating polymer-modified substrates with controlled graft densities were prepared by immobilizing various compositions of an initiator and a noninitiator followed by surface-initiated atom transfer radical polymerization of the self-oscillating polymer chains. In addition to the characterization of each prepared substrate, atomic force microscopy (AFM) and digital holographic microscopy (DHM) were employed to evaluate the density effects on the static and dynamic surface structures. AFM revealed that equilibrium swelling as well as thermoresponsive behavior is profoundly affected by the graft density. Moreover, using DHM, autonomous mechanical oscillation was captured only on the self-oscillating polymer brush with adequate graft density. Notably, the oscillation amplitude (150 nm) and the period (20 s) in this study were superior to those in a previous report on the self-oscillating polymer modified through the grafting-to method by 10- and 3-fold, respectively. This study presents design guidelines for future applications, such as autonomous transport devices.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 温度応答性高分子を利用した抗体医薬品分離技術の開発

    長瀬 健一,金澤 秀子

    B&I バイオサイエンスとインダストリー 79 ( 1 ) 38 - 39 2021.01

    Introduction and explanation (scientific journal), Joint Work,  ISSN  09148981

  • 刺激応答性高分子を用いたバイオセパレーション

    長瀬 健一,金澤 秀子

    高分子 69 ( 9 ) 472 - 473 2020.09

    Introduction and explanation (scientific journal), Joint Work

  • 効果的な心筋細胞シート移植のためのVEGF徐放ファイバーマットの開発

    長瀬健一, 金澤秀子

    Drug Delivery System (じほう)  34 ( 3 ) 173 - 178 2019.07

    Introduction and explanation (scientific journal), Joint Work,  ISSN  0913-5006

  • 微細構造表面と温度応答性高分子を用いた細胞分離技術の開発

    長瀬, 健一, 宿輪, 理紗, 小沼, 隆大, 大和, 雅之, 武田, 直哉 and 岡野, 光夫

    バイオマテリアル -生体材料- 36 ( 2 ) 158 - 159 2018.04

    Introduction and explanation (scientific journal), Joint Work

  • 積層化細胞シートの移植効率向上を目的とした細胞増殖因子徐放ファイバーマットの開発

    長瀬, 健一, 関根, 秀一, 清水, 達也, 金澤, 秀子, 岡野, 光夫, Lee, Seung Jin and 大和, 雅之

    Bioindustry (CMC出版)  35 ( 4 ) 36 - 45 2018.04

    Introduction and explanation (scientific journal), Joint Work

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Presentations 【 Display / hide

  • 簡便・安全な血清薬物試料の除タンパ クを可能にする温度応答性スピンカラムの開発

    井上正和, 石澤佑太, 金澤秀子, 長瀬健一

    日本分析化学会第70年会, 2021.09, Poster (general)

  • エクソソーム分離のための温度制御型アフィニティ精製法の開発

    山崎開智, 前川祐太朗, 山田創太, 金澤秀子, 長瀬健一

    日本分析化学会第70年会, 2021.09, Poster (general)

  • 細胞接着性ペプチドリガンドと生体適合性高分子を用いた温度制御型細胞分離法の開発

    島根瑠霞, 山田創太, 金澤秀子, 長瀬健一

    日本分析化学会第70年会, 2021.09, Poster (general)

  • 細胞移植効率化のための血管新生因子徐放ナノ粒子の開発

    永岡真凜, 中野雄斗, 山田創太, 鵜頭理恵, 金澤秀子, 長瀬健一

    LIFE2020-2021, 2021.09, Oral Presentation(general)

  • 温度応答性高分子とアフィニティリガンドを用いたエクソソーム精製法の開発

    山崎開智, 前川祐太朗, 山田創太, 金澤秀子, 長瀬健一

    第18回次世代を担う若手のためのフィジカル・ファーマフォーラム (PPF2020/PPF2021), 2021.09, Oral Presentation(general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 生体分子・細胞との相互作用を制御する革新的水圏機能材料の創製


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 長瀬 健一, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • 再生医療を革新的に効率化する機能性バイオ界面の創製


    MEXT, JSPS, 長瀬健一, 基盤研究(B) , Principal Investigator

  • 酸素産生ナノ粒子を用いた革新的細胞組織移植法の確立


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 長瀬 健一, Grant-in-Aid for Challenging Research (Exploratory) , Principal Investigator

  • mRNA送達による立体細胞組織内タンパク質発現を利用した脈管形成と血管新生誘導


    MEXT, JSPS, Grant-in-Aid for Scientific Research, 小林 純, Co-investigator

  • Development of Intelligent Cell Separation Materials with Cell Recognition


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 長瀬 健一, Grant-in-Aid for Scientific Research (C), Principal Investigator

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Awards 【 Display / hide

  • 高分子学会 広報委員会パブリシティ賞

    長瀬健一, 2021.08, 公益社団法人 高分子学会, 温度応答性-カチオン性ブロック共重合体による幹細胞分離法の開発

    Type of Award: Awards of National Conference, Council and Symposium.  Country: 日本

  • 第5回バイオインダストリー奨励賞

    長瀬健一, 2021.07, 一般財団法人バイオインダストリー協会, 機能性界面を用いたバイオ医薬品・治療用細胞 の革新的分離精製法の開発

    Type of Award: Other Awards.  Country: 日本

  • 学部長賞 研究部門


    Type of Award: Keio commendation etc.

  • 日本分析化学会 関東支部 新世紀賞


    Country: 日本

  • HPLC 2017 Jeju, Best Poster Award


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Courses Taught 【 Display / hide











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