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Japanese-German Joint Research on Real Time Monitoring Technology of Cellular Metabolism in Vitro Model Device

Research Project

Project/Area Number 18KK0306
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionKyoto University of Advanced Science (2019-2021)
Kyoto University (2018)

Principal Investigator

TABATA OSAMU  京都先端科学大学, 工学部, 教授 (20288624)

Co-Investigator(Kenkyū-buntansha) 亀井 謙一郎  京都大学, 高等研究院, 准教授 (00588262)
平井 義和  京都大学, 工学研究科, 講師 (40452271)
四竈 泰一  京都大学, 工学研究科, 准教授 (80456152)
山本 暁久  京都大学, 高等研究院, 特定助教 (90706805)
巽 和也  京都大学, 工学研究科, 准教授 (90372854)
Project Period (FY) 2018-10-09 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords生体模倣システム / 細胞代謝 / マイクロシステム / 量子センシング / リアルタイムモニタリング / オルガノイド / 細胞 / 細胞微小環境モデル / 生体外モデルデバイス / 生体外モデル / メタボリックシンドローム / Analytic BoC / リアルタイム計測 / 磁気共鳴イメージング
Outline of Final Research Achievements

The development of the fundamental technologies for realizing the Analytic-BoC newly proposed by the authors has been succeeded. Hirai and Tabata developed a microfluidic devices with fluid compliance elements capable of producing flow and pressure field transients. Kamei was succeeded to induce differentiation from hPSCs to liver organoids to introduce Analytic BoC. Shikama developed an endoscope and temperature sensor for a BoC device installed in a NMR sample holder. Tatsumi developed a cell encapsulation technique of almost 100% yield utilizing dielectrophoretic force for analyzing the single cell metabolic activity. Yamamoto has established analytical methods to characterize the active deformation and the color composition of stained images of cells and organoids, and has developed and evaluated novel microenvironment models.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は,圧力刺激を精密に制御した状態で肝臓オルガノイドを培養できる組織チップをNMR内の強磁場下に設置し,単一光ファイバ内視鏡を用いた広波長範囲レーザー分光とダイヤモンド粒子による非接触温度分布測定技術と組み合わせることで,オルガノイド表面の温度分布計測を可能にし,肝臓における疾病発現の機序を解明し,創薬や再生医療の発展に貢献することができる。さらに,この基盤技術に細胞の代謝活動を細胞ごとに並列・高速・高精度で分析可能な技術や,細胞・オルガノイドの変形モード解析や色相解析技術と組み合わせることで,創薬のみならず細胞の代謝活性や分化状態の評価に活用・展開できる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (39 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (5 results) Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 2 results) Presentation (18 results) (of which Int'l Joint Research: 11 results,  Invited: 4 results) Remarks (2 results) Funded Workshop (1 results)

  • [Int'l Joint Research] Karlsruher Institute of Technology/Ruprecht-Karls-Universitat Heidelberg(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] カールスルーエ工科大学/ハイデルベルグ大学(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] ジュネーブ大学(スイス)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] カールスルーエ工科大学/ハイデルベルク大学(ドイツ)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] カールスルーエ工科大学/ハイデルベルク大学(ドイツ)

    • Related Report
      2018 Research-status Report
  • [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] Increase of one-to-one particle encapsulation yield using dielectrophoretic alignment technique with boxcar-type electrodes2022

    • Author(s)
      MABUCHI Kenichi、TATSUMI Kazuya、KURIYAMA Reiko、NAKABE Kazuyoshi
    • Journal Title

      Transactions of the JSME (in Japanese)

      Volume: 88 Issue: 905 Pages: 21-00300-21-00300

    • DOI

      10.1299/transjsme.21-00300

    • NAID

      130008144344

    • ISSN
      2187-9761
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [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] Spatiotemporal determination of metabolite activities in the corneal epithelium on a chip2021

    • Author(s)
      Abdalkader Rodi、Chaleckis Romanas、Wheelock Craig E.、Kamei Ken-ichiro
    • Journal Title

      Experimental Eye Research

      Volume: 209 Pages: 108646-108646

    • DOI

      10.1016/j.exer.2021.108646

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Particle timing and spacing control in microchannel flow by applying periodic force over space and time2021

    • Author(s)
      Tatsumi Kazuya、Noma Atsushi、Honma Renato、Kuriyama Reiko、Nakabe Kazuyoshi
    • Journal Title

      Microfluidics and Nanofluidics

      Volume: 25 Issue: 2 Pages: 15-15

    • DOI

      10.1007/s10404-020-02416-5

    • Related Report
      2020 Research-status 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 Research-status 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
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recapitulation of Human Embryonic Heartbeat to Promote Differentiation of Hepatic Endoderm to Hepatoblasts2020

    • Author(s)
      Yoshimoto Koki、Minier Nicolas、Yang Jiandong、Imamura Satoshi、Stocking Kaylene、Patel Janmesh、Terada Shiho、Hirai Yoshikazu、Kamei Ken-ichiro
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 8 Pages: 1-11

    • DOI

      10.3389/fbioe.2020.568092

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A tesla-order magnetic field effect on all-optical thermometry using photoluminescence spectrum of diamond NV? center2020

    • Author(s)
      Shikama Taiichi、Watanabe Takato、Jouda Mazin、Hasuo Masahiro
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 60 Issue: 1 Pages: 012001-012001

    • DOI

      10.35848/1347-4065/abcadb

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells2020

    • Author(s)
      Poisa-Beiro Laura、Thoma Judith、Landry Jonathan、Sauer Sven、Yamamoto Akihisa、Eckstein Volker、Romanov Natalie、Raffel Simon、Hoffmann Georg F.、Bork Peer、Benes Vladimir、Gavin Anne-Claude、Tanaka Motomu、Ho Anthony D.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-020-68396-2

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed
  • [Journal Article] Particle Timing Control and Alignment in Microchannel Flow by Applying Periodic Force Control Using Dielectrophoretic Force2019

    • Author(s)
      Tatsumi Kazuya、Kawano Koki、Shintani Hiromichi、Nakabe Kazuyoshi
    • Journal Title

      Analytical Chemistry

      Volume: 10.1021 Issue: 10 Pages: 1-9

    • DOI

      10.1021/acs.analchem.8b04821

    • NAID

      120006726148

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [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)
    • 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
    • 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
    • Related Report
      2021 Annual Research Report
  • [Presentation] Alignment and Timing Control of Particles in Microchannel Flow Using Dielectrophoretic Force2021

    • Author(s)
      Kazuya Tatsumi
    • Organizer
      2nd Asian Conference on Thermal Science (ACTS-2)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Toward 100% Yield of One-to-One Particle Encapsulation Using Dielectrophoretic Particle Alignment Technique2021

    • Author(s)
      Kazuya Tatsumi, Kenichi Mabuchi, Reiko Kuriyama, Kazuyoshi Nakabe
    • Organizer
      7th Micro and Nano Flows Conference (MNF2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Measurement of Trans-Epithelial Electrical Resistance in Organ-on-a-Chip2020

    • 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)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] In Vitro Modeling of Non-Alcoholic Fatty Liver Disease by Integrated Gut-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 and Exhibit, Online (December, 2020)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [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)
    • Related Report
      2020 Research-status 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-NEMS2020)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [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, 田畑修, 土屋智由
    • 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
    • Related Report
      2020 Research-status 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
    • Related Report
      2020 Research-status 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
    • Related Report
      2020 Research-status Report
  • [Presentation] マイクロ流路内での1液滴1粒子封入の100%収率を目指して2020

    • Author(s)
      馬淵研一,栗山怜子, 巽和也, 中部主敬
    • Organizer
      流体力学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Timing Control and Alignment of Particles in Microchannel Flow Using Dielectrophoretic Forces2019

    • Author(s)
      Kazuya. Tatsumi, Atsuhi Noma, Renato Honma, Reiko Kuriyama, Kazuyoshi Nakabe
    • Organizer
      2nd Pacific Rim Thermal Engineering Conference (PRTEC 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Timing, Spacing and Velocity Control of Particles and Cells in Microchannel Flow - A Microfluidic Pitching Machine2019

    • Author(s)
      Kazuya Tatsumi
    • Organizer
      Workshop on Optofluidics and Electrokinetics 2019 (OEMN 2019)
    • Related Report
      2019 Research-status 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 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マルチモードファイバ内視鏡の変形に伴う空間分解能低下に対する影響の評価2019

    • Author(s)
      石川 理沙,四竈 泰一,蓮尾 昌裕
    • Organizer
      第80回 応用物理学会秋季学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] Three Dimensional UV Lithography Technologies for Microphysiological Systems2018

    • Author(s)
      Yoshikazu Hirai
    • Organizer
      The 31st International Microprocesses and Nanotechnology Conference (MNC 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] Hekksagon

    • URL

      http://www.oc.kyoto-u.ac.jp/network/hekksagon/

    • Related Report
      2020 Research-status Report 2019 Research-status Report
  • [Remarks] HeKKSaGOn

    • URL

      http://www.oc.kyoto-u.ac.jp/network/hekksagon/

    • Related Report
      2018 Research-status Report
  • [Funded Workshop] of Cellular MetabolismWorkshop on “Creation of Real Time Monitoring Technology in Vitro Model Device”2020

    • Related Report
      2020 Research-status Report

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Published: 2018-10-12   Modified: 2023-01-30  

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