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肝細胞スフェロイドチップの開発

Research Project

Project/Area Number 18860017
Research Category

Grant-in-Aid for Young Scientists (Start-up)

Allocation TypeSingle-year Grants
Research Field Biofunction/Bioprocess
Research InstitutionUniversity of Tsukuba

Principal Investigator

福田 淳二  University of Tsukuba, 大学院・数理物質科学研究科, 講師 (80431675)

Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥2,760,000 (Direct Cost: ¥2,760,000)
Fiscal Year 2007: ¥1,370,000 (Direct Cost: ¥1,370,000)
Fiscal Year 2006: ¥1,390,000 (Direct Cost: ¥1,390,000)
Keywords肝細胞 / スフェロイド / 細胞チップ / フォトリソグラフィ / マイクロコンタクトプリンティング / アンモニア代謝 / 創薬スクリーニング / 薬物代謝酵素 / RGDペプチド
Research Abstract

一年目には、細胞チップによる測定結果の信頼性を左右する最も重要な因子が細胞の生存状態であると考え、良好な生存状態が維持される3次元細胞組織体をチップ上に自発的に形成・マイクロアレイ化する技術を開発した。
そこで2年目は、チップ上における細胞機能解析技術を開発した。この細胞チップには、電気化学的原理を利用したマイクロポンプとセンサを集積化し、培養から測定までの一連の作業をワンチップ上で行える機能測定システムとした。特に、一回のサンプリング量を12nlと極微量に制御し、電気的なスイッチを押すだけでサンプリングおよび測定がおこなわれるよう設計することで、インキュベータ中に培養系を静置したまま、短い間隔で連続的なモニタリングを実現した。実際に機能計測の例として、肝細胞のアンモニア代謝機能をモニタリング可能であることを示した。肝細胞の播種密度11cells/mm^2において、1mMのアンモニアが3時間後には0.27mMまで低下する様子をモニタリングし、通常のディッシュ上で培養し市販キットにより3時間後のみを測定したときと良く一致することが示された。従来の測定法と異なり、本チップでは煩雑な前処理無しに、高い時間分解能で自動的な測定が可能となった。また、本システムでは、送液、センシングをすべて電気化学的原理に基づいて構築しているため、微小化、集積化に適している。チップ挿入ロをもつハンディタイプの分析機器への展開を目指し検討を続けている。
本研究に関連する成果は、本研究課題の研究期間である平成18年度および平成19年度で原著英語論文21報に結実した。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (28 results)

All 2008 2007 2006 Other

All Journal Article (21 results) (of which Peer Reviewed: 8 results) Presentation (4 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Automatic Electrochemical Micro-pH-Stat for Biomicrosystems2008

    • Author(s)
      K. Morimoto, M. Toya, J. Fukuda, and H. Suzuki
    • Journal Title

      Analytical chemistry 80(4)

      Pages: 905-14

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver2007

    • Author(s)
      M. Shimada, Y. Yamashita, S. Tanaka, K. Shirabe, K. Nakazawa, H. Ijima, R. Sakiyama, J. Fukuda, K. Funatsu, K. Sugimachi
    • Journal Title

      Hepatogastroenterology 54(75)

      Pages: 814-20

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] On-chip handling of solutions and electrochemiluminescence detection of amino acids2007

    • Author(s)
      H. Hosono, W. Satoh, J. Fukuda, H. Suzuki
    • Journal Title

      Sensors and Actuators B 122(2)

      Pages: 542-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemical microsystem with porous matrix packed beds for enzyme analysis2007

    • Author(s)
      K. Morimoto, S. Upadhyay, T. Higashiyama, N. Ohgami, H. Kusakabe, J. Fukuda, H. Suzuki
    • Journal Title

      Sensors and Actuators B 124(2)

      Pages: 477-85

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Electrochemical immunoassay on a microfluidic device with sequential injection and flushing functions2007

    • Author(s)
      N. Nashida, W. Satoh, J. Fukuda, and H. Suzuki
    • Journal Title

      Biosensors and Bioelectronics 22(12)

      Pages: 3167-73

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enzyme Electrode Formed by Evaporative Concentration and its Perfor mance Characterization2007

    • Author(s)
      M. Hashimoto, N. Sakamoto, S. Upadhyay, J. Fukuda, and H. Suzuki
    • Journal Title

      Biosensors and Bioelectronics 22(12)

      Pages: 3154-60

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Micro Analysis System Based on Electrochemiluminescence Detection2007

    • Author(s)
      H. Hosono, W. Satoh, J. Fukuda, and H. Suzuki
    • Journal Title

      Sensors and Materials 19(4)

      Pages: 191-201

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Controlling size, shape and homogeneity of embryoid bodies using poly(ethylene glycol)microwells2007

    • Author(s)
      J. Karp, J. Yeh, G. Eng, J .Fukuda, J. Blumling, K. Y. Suh, J. Cheng, A. Mahdavi, J. Borenstein, R. Langer and A. Khademhosseini
    • Journal Title

      Lab on a Chip 7

      Pages: 786-94

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel hepatocyte culture system by using micro-fabrication and collagen/PEG micro-contact printing2007

    • Author(s)
      J.Fukuda, Y.Sakai, K.Nakazawa
    • Journal Title

      Biomaterials 27・7

      Pages: 1061-70

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Galactose-PEG dual conjugation of β-(1→3)-D-glucan schizophyllan for antisense oligonucleotides delivery to enhance the cellular uptake2006

    • Author(s)
      R.Karinaga, T.Anada, M.Mizu, K.Koumoto, J.Fukuda, K.Nakazawa, T.Hasegawa, M.Mumata, S.Shinkai, K.Sakurai
    • Journal Title

      Biomaterials 27・8

      Pages: 1626-35

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatocyte spheroid formation on a titanium dioxide gel surface and hepatocyte long-term culture2006

    • Author(s)
      K.Nakazawa, S-W.Lee, J.Fukuda, D-H.Yang, T.Kunitake
    • Journal Title

      Journal of Materials Science : Materials in Medicine 14・4

      Pages: 359-64

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Micropatterned cell co-cultures using layer-by-layer deposition of extracellular matrix components2006

    • Author(s)
      J.FUkuda, A.Khademhosseini, J.Yeh, G.Eng, J.Cheng, O.Farokhzad, R.Langer
    • Journal Title

      Biomaterials 27・8

      Pages: 1479-86

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Interplay of biomaterials and micro-scale technologies for advancing biomedical applications2006

    • Author(s)
      A.Khademhosseini, C.Bettinger, J.Karp, J.Yeh, Y.Ling, J.Borenstein, J.Fukuda, R.Langer
    • Journal Title

      Journal of Biomaterials Science : Polymer Edition 17・11

      Pages: 1221-40

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Micromolding of photocrosslinkable chitosan hydrogel for spheroid microarray and co-cultures2006

    • Author(s)
      J.Fukuda, A.Khademhosseini, Y.Yeo, X.Yang, J.Yeh, G.Eng, J.Blumling, CF Wang, D.Kohane, R.Langer
    • Journal Title

      Biomaterials 27・30

      Pages: 5295-67

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment2006

    • Author(s)
      A.Khademhosseini, G.Eng, J.Yeh, J.Fukuda, J.3rd Blumling, R.Langer, JA.Burdick
    • Journal Title

      Journal Biomedical Materials Research A 79・3

      Pages: 522-32

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Co-culture of Human Embryonic Stem Cells with Murine Embryonic Fibroblasts on Microwell Patterned Substrates2006

    • Author(s)
      A.Khademhosseini, L.Ferreira, J.Blumling III, J.Yeh, J.Karp, J.Fukuda, R.Langer
    • Journal Title

      Biomaterials 27・36

      Pages: 5968-77

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hepatocyte spheroid culture on a poly-dimethylsiloxane chip having microcavities

    • Author(s)
      K.Nakazawa, Y.Izumi, J.Fukuda, T.Yasuda
    • Journal Title

      Journal of Biomaterials Science-polymer edition in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] On-chip handling of solutions and electrochemiluminescence detection of amino acids

    • Author(s)
      H.Hosano, W.Satoh, J.Fukuda, H.Suzuki
    • Journal Title

      Sensors and Actuators B in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Electrochemical microsystem with porous matrix packed beds for enzyme analysis

    • Author(s)
      K.Morimoto, S.Upadhyay, T.Higashiyama, N.Ohgami, H.Kusakabe, J.Fukuda, H.Suzuki
    • Journal Title

      Sensors and Actuators B in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Electrochemical immunoassay on a microfluidic device with sequential injection and flushing functions

    • Author(s)
      N.Nashida, W.Satoh, J.Fukuda, H.Suzuki
    • Journal Title

      Biosensors and Bioelectronics in press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Enzyme Electrode Formed by Evaporative Concentration and its Performance Characterization

    • Author(s)
      M.Hashimoto, N.Sakamoto, S.Upadhyay, J.Fukuda, H.Suzuki
    • Journal Title

      Sensors and Actuators B in press

    • Related Report
      2006 Annual Research Report
  • [Presentation] 電気化学的原理に基づくティッシュ・エンジニアリング2008

    • Author(s)
      福田淳二、稲葉里奈、瀬戸祐希、鈴木博章
    • Organizer
      日本再生医療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-03-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] Micro Analysis System for Digestive Enzymes Based on Integrated Automatic pH-Stats2007

    • Author(s)
      K. Morimoto, J. Fukuda, H. Suzuki
    • Organizer
      IEEE Sensors 2007
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2007-10-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] Microfluidic Device for on-Chip Manipulation of Liquid Plugs for Biosensing Applications2007

    • Author(s)
      K. Morimoto, J. Fukuda, H. Suzuki
    • Organizer
      IEEE Sensors 2007
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2007-10-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] Microanalysis system based on electrochemiluminescence with automaticmixing and pH-regulation functions2007

    • Author(s)
      W. Satoh, H. Hosono, M. Toya, K. Morimoto, J. Fukuda, and H. Suzuki
    • Organizer
      Transducers '07
    • Place of Presentation
      Lyon, France
    • Year and Date
      2007-06-14
    • Related Report
      2007 Annual Research Report
  • [Book] 動物実験代替のためのバイオマテリアル開発(部分執筆: 細胞外マトリックスを用いたマイクロパターン細胞共培養システム)2007

    • Author(s)
      福田淳二、鈴木博章
    • Total Pages
      250
    • Publisher
      シーエムシー出版
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.trios.tsukuba.ac.jp/Profiles/0003/0002247/profile.html

    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 培養方法及び培養装置2007

    • Inventor(s)
      福田淳二、鈴木博章、稲葉里奈、岡村健太郎
    • Industrial Property Rights Holder
      筑波大学
    • Industrial Property Number
      2007-145786
    • Filing Date
      2007-05-31
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2016-04-21  

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