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"Body-on-a-chip" integrated recirculation system mimicking human body rhythms

Research Project

Project/Area Number 19H02572
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 28050:Nano/micro-systems-related
Research InstitutionKyoto University

Principal Investigator

Hirai Yoshikazu  京都大学, 工学研究科, 講師 (40452271)

Co-Investigator(Kenkyū-buntansha) 亀井 謙一郎  京都大学, 高等研究院, 准教授 (00588262)
田畑 修  京都先端科学大学, 工学部, 教授 (20288624)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsBody on a Chip / 組織チップ / マイクロ流体デバイス / 圧力センサ / 微細加工 / グレースケールリソグラフィ / 設計工学
Outline of Research at the Start

本研究は、ヒトの体内循環における臓器間の相互作用と生体リズムを高度に模倣した新しい生体外実験モデル「ボディ・オン・チップ」を開発する。本チップを構成するマイクロ流体デバイスの特徴は、小さなチップ内で生体リズムを模倣するために周期変動する流れ場・圧力場を形成するアクチュエータ、またそれらをフィードバック制御するためのセンサを集積している点である。細胞アッセイ実験により当該研究の有用性を示すとともに、多臓器疾患の解明研究や創薬基盤技術の構築へとつなげる。

Outline of Final Research Achievements

We developed fluid control elements (sensors and actuators) to form, precisely measure and control the pressure field of cell medium required to mimic biological rhythms in a body-on-a-chip. In addition, to reproduce human physiological and pathological conditions in vivo, we developed a method to induce differentiation of human pluripotent stem cells into more functional target tissues.Furthermore, cell assay experiments revealed the superiority of mimicking biological rhythms by applying various physical stimuli in the microenvironment of a body-on-chip based on a microfluidic device. These results contribute to the development of advanced body-on-chips that can be applied to research to investigate the mechanism of multi-organ disease progression, which is difficult to analyze with conventional simple organ/body-on-a-Chip models.

Academic Significance and Societal Importance of the Research Achievements

新規薬剤の開発コストの増大と臨床試験の成功率の低下が顕著である。ヒトの体内システムを部分的に模倣し、動物実験とのギャップを補完する生体外実験モデル「ボディ・オン・チップ」はその解決策として有効なツールである。本研究は、ボディ・オン・チップで体内システムを高度に模倣するための要素技術を、マイクロ工学と幹細胞工学の双方で達成した点に学術的意義がある。これらの要素技術を統合したボディ・オン・チップは、将来的に糖尿病や非アルコール性脂肪性肝疾患の発症メカニズムなどの多臓器疾患の解明研究や創薬基盤技術の構築につながることが期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (22 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 1 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 2 results)

  • [Journal Article] In vitro culture at 39?°C during hepatic maturation of human ES cells facilitates hepatocyte-like cell functions2022

    • Author(s)
      Imamura Satoshi、Yoshimoto Koki、Terada Shiho、Takamuro Kaho、Kamei Ken-ichiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 5155-5160

    • DOI

      10.1038/s41598-022-09119-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Design Method of Organ-on-a-Chip with Highly Accurate Measurement of Trans-Epithelial Electrical Resistance2021

    • Author(s)
      Miyazaki Takashi、Hirai Yoshikazu、Kamei Ken-ichiro、Tsuchiya Toshiyuki、Tabata Osamu
    • Journal Title

      IEEJ Transactions on Sensors and Micromachines

      Volume: 141 Issue: 7 Pages: 237-244

    • DOI

      10.1541/ieejsmas.141.237

    • NAID

      130008060178

    • ISSN
      1341-8939, 1347-5525
    • Year and Date
      2021-07-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design Strategy of Electrode Patterns Based on Finite Element Analysis in Microfluidic Device for Trans-Epithelial Electrical Resistance (TEER) Measurement2020

    • Author(s)
      Miyazaki Takashi、Hirai Yoshikazu、Kamei Ken-ichiro、Tsuchiya Toshiyuki、Tabata Osamu
    • Journal Title

      IEEJ Transactions on Sensors and Micromachines

      Volume: 140 Issue: 10 Pages: 285-292

    • DOI

      10.1541/ieejsmas.140.285

    • NAID

      130007920655

    • ISSN
      1341-8939, 1347-5525
    • Year and Date
      2020-10-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design strategy of electrode patterns based on finite element analysis in microfluidic device for Trans‐Epithelial Electrical Resistance (TEER) measurement2020

    • Author(s)
      Miyazaki Takashi、Hirai Yoshikazu、Kamei Ken‐ichiro、Tsuchiya Toshiyuki、Tabata Osamu
    • Journal Title

      Electronics and Communications in Japan

      Volume: 104 Issue: 2 Pages: 285-292

    • DOI

      10.1002/ecj.12296

    • NAID

      130007920655

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Microfluidic Device Integrated with a Fluidic-Capacitor to Mimic Heart Beating for Generation of Functional Liver Organoids2019

    • Author(s)
      Wu Jiaxu、Hirai Yoshikazu、Kamei Ken-ichiro、Tsuchiya Toshiyuki、Tabata Osamu
    • Journal Title

      IEEJ Transactions on Sensors and Micromachines

      Volume: 139 Issue: 7 Pages: 209-216

    • DOI

      10.1541/ieejsmas.139.209

    • NAID

      130007671301

    • ISSN
      1341-8939, 1347-5525
    • Year and Date
      2019-07-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel microfluidic device integrated with a fluidic‐capacitor to mimic heart beating for generation of functional liver organoids2019

    • Author(s)
      Wu Jiaxu、Hirai Yoshikazu、Kamei Ken‐Ichiro、Tsuchiya Toshiyuki、Tabata Osamu
    • Journal Title

      Electronics and Communications in Japan

      Volume: 102 Issue: 10 Pages: 41-49

    • DOI

      10.1002/ecj.12210

    • NAID

      130007671301

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Multilayered Microfluidic Device for Controllable Flow Perfusion of Gut-Liver on a Chip2021

    • Author(s)
      Jiandong Yang, Satoshi Imamura, Yoshikazu Hirai, Ken-ichiro Kamei, Toshiyuki Tsuchiya, Osamu Tabata
    • Organizer
      The 21st International Conference on Solid-State Sensors Actuators and Microsystems (Transducers 2021), Online (June 20-25, 2021), pp. 176-179
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 心臓拍動を模倣した圧力刺激印加による肝オルガノイド成熟化を目指すマイクロ流体デバイス2021

    • Author(s)
      三浦大知, 平井義和, 亀井謙一郎, 土屋智由
    • Organizer
      化学とマイクロ・ナノシステム学会第43回研究会, 化学とマイクロ・ナノシステム学会, オンライン, 2021年5月, 1P-06
    • Related Report
      2021 Annual Research Report
  • [Presentation] Gut-Liver on a Chip With Controllable Flow Perfusion via Multilayered Microfluidic Device2021

    • Author(s)
      楊建東, 今村聡, 平井義和, 亀井謙一郎, 土屋智由, 田畑修
    • Organizer
      第38回「センサ・マイクロマシンと応用システム」シンポジウム, 電気学会, オンライン, 2021年11月, 10P2-SS1-2
    • Related Report
      2021 Annual Research Report
  • [Presentation] Highly Accurate Measurement of Trans-Epithelial Electrical Resistance in Organ-on-a-Chip2021

    • Author(s)
      Takashi Miyazaki, Jiandong Yang, Satoshi Imamura, Yoshikazu Hirai, Ken-ichiro Kamei, Toshiyuki Tsuchiya, Osamu Tabata
    • Organizer
      The 34th IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2021), Online (January 25-29, 2021), pp. 411-414
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic Platform Fabricated by Three-Dimensional Lithography Enables Drug Test and Disease Modeling in vitro2020

    • Author(s)
      Yoshikazu Hirai
    • Organizer
      The 15th IEEE International Conference on Nano/Micro Engineered and Molecular Systems (IEEE-NEMS 2020), Online (September 27-30, 2020), pp. 360
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Heart-Liver on a Chip Integrated with a Microelectrode Array to Monitor Extracellular Field Potentials of Cardiomyocytes2020

    • Author(s)
      Dongxiao Zhang, Yoshikazu Hirai, Ken-ichiro Kamei, Osamu Tabata, Toshiyuki Tsuchiya
    • Organizer
      The 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020), Online (October 4-9, 2020), pp. 941-942
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In Vitro Modeling of Non-Alcoholic Fatty Liver Disease by IntegratedGut-Liver on a Chip2020

    • Author(s)
      Jiandong Yang, Yoshikazu Hirai, Ken-ichiro Kamei, Marika Trumm, Toshiyuki Tsuchiya, Osamu Tabata
    • Organizer
      The 2020 MRS Spring/Fall Meeting, Online (November 27-December 4, 2020), S.SM01.02.02
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 電流密度解析を用いた経上皮電気抵抗計測用微小電極アレイの設計2020

    • Author(s)
      宮崎貴史, 平井義和, 亀井謙一郎, 田畑修, 土屋智由
    • Organizer
      第30回マイクロエレクトロニクスシンポジウム(MES2020), エレクトロニクス実装学会, オンライン, 2020年9月, 2B4-3
    • Related Report
      2020 Annual Research Report
  • [Presentation] 経上皮電気抵抗測定の高精度化に向けたOrgans-on-a-Chipの設計法2020

    • Author(s)
      宮崎貴史, 平井義和, 亀井謙一郎, 土屋智由, 田畑修
    • Organizer
      第37回「センサ・マイクロマシンと応用システム」シンポジウム, 電気学会, オンライン, 2020年10月, 27P2-SS1-3
    • Related Report
      2020 Annual Research Report
  • [Presentation] 細胞外電位計測を目的としたパリレン製微小電極アレイのボディ・オン・チップへの集積2020

    • Author(s)
      張東暁, 平井義和, 亀井謙一郎, 田畑修, 土屋智由
    • Organizer
      第11回マイクロ・ナノ工学シンポジウム, 日本機械学会, オンライン, 2020年10月, 26P2-MN1-2
    • Related Report
      2020 Annual Research Report
  • [Presentation] 非アルコール性脂肪性肝疾患を再現する肝臓-小腸・オン・チップ2020

    • Author(s)
      亀井謙一郎, 楊建東, 飯田慶, 寺田志穂, 土屋智由, 田畑修, 平井義和
    • Organizer
      化学とマイクロ・ナノシステム学会第42回研究会, 化学とマイクロ・ナノシステム学会, オンライン, 2020年10月, 2P20
    • Related Report
      2020 Annual Research Report
  • [Presentation] Characterization of Ionic Liquid-Based Pressure Sensor Fabricated by Grayscale Lithography2019

    • Author(s)
      Yusuke Tsuji, Yoshikazu Hirai, Ken-ichiro Kamei, Toshiyuki Tsuchiya, Osamu Tabata
    • Organizer
      The 14th IEEE International Conference on Nano/Micro Engineered and Molecular Systems (IEEE-NEMS 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integrated Gut-Liver on a Chip for Modelling Non-Alcoholic Fatty Liver Disease in vitro2019

    • Author(s)
      Jiandong Yang, Yoshikazu Hirai, Ken-ichiro Kamei, Toshiyuki Tsuchiya, Osamu Tabata
    • Organizer
      The 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PDMS-integratable Ionic Liquid-based Pressure Sensor for Microphysiological Systems2019

    • Author(s)
      Yoshikazu Hirai
    • Organizer
      The 5th International Conference on Advanced Electromaterials (ICAE 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] PDMS製マイクロ流体デバイスへ実装可能な高感度イオン液体型圧力センサ2019

    • Author(s)
      辻勇亮, 平井義和, 亀井謙一郎, 土屋智由, 田畑修
    • Organizer
      第29回マイクロエレクトロニクスシンポジウム(MES2019)
    • Related Report
      2019 Annual Research Report
  • [Presentation] A Microfluidic Gut-Liver on a Chip for Modeling the Non-Alcoholic Fatty Liver Disease2019

    • Author(s)
      Jiandong Yang, Yoshikazu Hirai, Ken-ichiro Kamei, Toshiyuki Tsuchiya, Osamu Tabata
    • Organizer
      化学とマイクロ・ナノシステム学会第40回研究会
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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