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Development of a novel liquid biopsy platform by combining microfluidics and integrated circuits

Research Project

Project/Area Number 19H02569
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 InstitutionThe University of Tokyo

Principal Investigator

KIM SooHyeon  東京大学, 生産技術研究所, 講師 (80709189)

Co-Investigator(Kenkyū-buntansha) 長阪 一憲  帝京大学, 医学部, 教授 (30624233)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsフローサイトメトリー / シリコン集積回路チップ / マイクロ流体デバイス / リキッドバイオプシー / 1細胞解析 / セルソーター / 1細胞解析
Outline of Research at the Start

本研究では、体液中のがん細胞を検出・分離し、一細胞解析を行う、次世代リキッドバイオプシープラットフォームの確立を目指す。これにより将来的には、患者の体液からがん細胞の同定・シグネチャー解析を一細胞レベルで定期的に行うことで、抗がん剤や手術などの治療効果をリアルタイムで評価できるようになるだけではなく、がんの変異的特徴の時系列変化を調べることが出来る。

Outline of Final Research Achievements

We developed a novel concept of parallelized flow cytometer which consists of an array of Single Photon Avalanche Diode (SPAD) aligned with parallelized microfluidic channels. The fluorescence signal from individual cells flowing each microfluidic channel were simultaneously detected with the SPADs by separating emission from excitation in time domain without a complex microscopy system. Moreover, by integrating microfluidics and CMOS technologies, a novel microfluidic system has been developed for trapping single cells and/or microparticles into designated locations, followed by parallelized analysis of trapped single cells. By integrating these technologies, we expect to establish a novel liquid biopsy platform capable of highly efficient separation and analysis of cancer cells from body fluids.

Academic Significance and Societal Importance of the Research Achievements

細胞を高効率で同定できるフローサイトメトリー分野においては高速化に関する研究が行われているが、一本のキャピラリーを用いた既存の方法ではその物理的な限界があり、現状以上にスループットを向上するのは困難である。本研究は、発想を変えてフローサイトメーターを並列化することで、フローサイトメーターの機能・スループットの高度化を図るものであり、フローサイトメトリーの新たな展開を拓くことが期待できる。

Report

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

    (17 results)

All 2021 2020 2019

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 7 results,  Invited: 5 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Morphological manipulation of DNA gel microbeads with biomolecular stimuli2021

    • Author(s)
      S. Okumura, N. Benediktus, N. Lobato-Dauzier, Y. Ohno, S. Benner, Y. Torii, Y. Tanabe, K. Takada, A. Baccouche, M. Shinohara, S. H. Kim, T. Fujii, A. Genot
    • Journal Title

      Nanomaterials

      Volume: 11 Issue: 2 Pages: 1-16

    • DOI

      10.3390/nano11020293

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sequential Cell-Processing System by Integrating Hydrodynamic Purification and Dielectrophoretic Trapping for Analyses of Suspended Cancer Cells2019

    • Author(s)
      Park Jongho、Komori Takayuki、Uda Toru、Miyajima Keiichi、Fujii Teruo、Kim Soo Hyeon
    • Journal Title

      Micromachines

      Volume: 11 Issue: 1 Pages: 47-47

    • DOI

      10.3390/mi11010047

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] On-chip immunofluorescence analysis of single cervical cells using an electroactive microwell array with barrier for cervical screening2019

    • Author(s)
      Takeuchi Makoto、Nagasaka Kazunori、Yoshida Mina、Kawata Yoshiko、Miyagawa Yuko、Tago Saori、Hiraike Haruko、Wada-Hiraike Osamu、Oda Katsutoshi、Osuga Yutaka、Fujii Tomoyuki、Ayabe Takuya、Kim Soo Hyeon、Fujii Teruo
    • Journal Title

      Biomicrofluidics

      Volume: 13 Issue: 4 Pages: 044107-044107

    • DOI

      10.1063/1.5089796

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Two-dimensional flow cytometry realized by using an array of time-gated single photon avalanche diodes2021

    • Author(s)
      S. Tago, K. Iizuka, T. Mitsunaka, D. Sato, T. Shindo, T. Fujii and S. H. Kim
    • Organizer
      MicroTAS2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Advanced biomedical microsystems for single-cell analysis2021

    • Author(s)
      Soo Hyeon Kim
    • Organizer
      IEEE-NEMS 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Overcome the limits of cell analysis using advanced microfluidics-on-CMOS device2021

    • Author(s)
      Soo Hyeon Kim
    • Organizer
      Pittcon 2021
    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Microfluidics-on-CMOSシステムによる高精度1細胞解析2021

    • Author(s)
      Soo Hyeon Kim
    • Organizer
      SCE2021 第41回キャピラリー電気泳動シンポジウム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Precise analysis of single molecules and cells using microsystems2021

    • Author(s)
      Soo Hyeon Kim
    • Organizer
      International Symposium on Upcoming Prominent ENgineering solutions
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Parallelized flow cytometry realized by array of time- gated single photon avalanche diodes2020

    • Author(s)
      C. Trzeciakowski, D. Sato, T. Shindo, T. Mitsunaka, Y. Fujimoto, K. Iizuka, S. Tago, T. Fujii and S. H. Kim
    • Organizer
      MicroTAS2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SPADアレイを用いた並列フローサイトメトリー2019

    • Author(s)
      田子沙織、藤井輝夫、金秀炫
    • Organizer
      第47回可視化情報シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] がん細胞塊トランスクリプトーム解析を目的とした細胞塊選別と液滴生成機能一体システムの開発2019

    • Author(s)
      齊藤大哲、金秀炫、土屋一成、関真秀、永澤慧、駒崎友亮、鳥居徹、鈴木穣、藤井輝夫
    • 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
  • [Presentation] マイクロ流体アプローチによる高感度Liquid Biopsy技術の進展2019

    • Author(s)
      金秀炫、藤井輝夫
    • Organizer
      第4回 Liquid Biopsy 研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Integrated parallel flow cytometry device with time gated spads2019

    • Author(s)
      D. Sato, T. Shindo, T. Mitsunaka, Y. Fujimoto, K. Iizuka, S. Tago, Y. Takayama, T. Fujii and S. H. Kim
    • Organizer
      Transducers 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integration of on-chip cluster purification and compartmentalization for rna-seq analysis of clusters2019

    • Author(s)
      H. Saito, S. H. Kim, I. Tsuchiya, S. Nagasawa, M. Seki, Y. Komazaki, T. Torii, Y. Suzuki and T. Fujii
    • Organizer
      International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 流路デバイス、流体中粒子解析システムおよび流体中粒子分別システム2020

    • Inventor(s)
      佐藤大紀、金秀炫
    • Industrial Property Rights Holder
      佐藤大紀、金秀炫
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-158646
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 生体粒子捕集装置2019

    • Inventor(s)
      満仲健、飯塚邦彦、幡井徹也、藤井輝夫、金秀炫
    • Industrial Property Rights Holder
      満仲健、飯塚邦彦、幡井徹也、藤井輝夫、金秀炫
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-192797
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 流路デバイスおよび流体中粒子解析システム2019

    • Inventor(s)
      飯塚邦彦、藤井輝夫、金秀炫
    • Industrial Property Rights Holder
      飯塚邦彦、藤井輝夫、金秀炫
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-180308
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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

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