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Demonstration of a multiscale fluid separator that revolutionizes next-generation liquid biopsy

Research Project

Project/Area Number 19H02520
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionChiba University

Principal Investigator

Yamada Masumi  千葉大学, 大学院工学研究院, 准教授 (30546784)

Co-Investigator(Kenkyū-buntansha) 関 実  千葉大学, 大学院工学研究院, 教授 (80206622)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Keywordsマイクロ流体デバイス / 多孔性基材 / 細胞分離 / リキッドバイオプシー / エクソソーム / 生物化学工学
Outline of Research at the Start

本研究では,血液中に存在する生体粒子をマーカーとして利用する疾患の診断技術「リキッドバイオプシー」に革新をもたらす新規分離精製手法を開発する。具体的には,細胞などの生体粒子を連続的に導入するだけで,特定の生体粒子のみを選抜できる「マルチスケール流体セパレーター」を提案する。様々な大きさ・性質を有する粒子に対応できる流路構造の作製方法を確立し,さらに本分離精製手法の機能化および生化学解析操作との融合によって,エクソソームや希少細胞などの生体粒子分離における有用性を実証する。

Outline of Final Research Achievements

We developed new microfluidic devices for efficient separation and selection of rare cells and microparticles in blood samples for liquid biopsy. We developed a fabrication method for porous silicone substrates using soluble microparticles as sacrificial materials, a process for integrating the porous substrate into a fluidic device, and investigated the optimal conditions for fabricating multiscale microfluidic devices. Separation experiments targeting blood cells were conducted, and it was confirmed that relatively high throughputs of about 1 mL/min was achieved, and that particle separation with submicron-sized threshold was realized. Furthermore, we were able to develop systems for selective capture of rare cells, visualization of intracellular molecules, and solution exchange of cell suspensions.

Academic Significance and Societal Importance of the Research Achievements

マイクロ流体デバイスを用い,細胞や微粒子を物理・化学的な性質に基づいて分離するための手法がこれまでに多数報告されてきた。しかしながら,特に疾患の診断を目的として特定の細胞や微粒子を生体サンプルから分離する上で,処理量,分離精度,装置の作製コスト,などの点で課題があった。本研究ではこれらの課題を解決するため,これまでに報告されていない「多孔性基材を簡便に組み込んだマイクロ流体デバイス」を作製し,特定の細胞や血液成分の分離に適用した。処理量の向上,小さい分離対象の正確な分離,などを実現することができたため,将来的には疾患の診断などにおいて有用な装置として広く利用可能であると期待される。

Report

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

    (33 results)

All 2022 2021 2020 2019 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (24 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results) Remarks (2 results)

  • [Journal Article] Process Simplification and Structure Design of Parallelized Microslit Isolator for Physical Property-based Capture of Tumor Cells2022

    • Author(s)
      Natsumi Shimmyo, Mayu Furuhata, Masumi Yamada*, Rie Utoh, and Minoru Seki
    • Journal Title

      Analyst

      Volume: 147 Issue: 8 Pages: 1622-1630

    • DOI

      10.1039/d2an00052k

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microfluidic Particle Sorting System Integrated with Spherically-pored PDMS Sponges as Sieving Matrices2021

    • Author(s)
      Runa Hemmi, Takeru Sato, Masumi Yamada, and Minoru Seki
    • Journal Title

      Proceedings of the 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)

      Volume: - Pages: 1175-1176

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Parallelized Microfluidic Thin Cell Trappers for Effectively Selecting Blood Circulating Tumor Cells2020

    • Author(s)
      Natsumi Shimmyo, Makoto Furuhata, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Journal Title

      Proceedings of the 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)

      Volume: - Pages: 1155-1156

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microfluidic Medium Exchanger with Micropored Fluid Drainage for Cell Culture Applications2020

    • Author(s)
      Takeru Sato, Yurika Sakurai, Masumi Yamada, and Minoru Seki
    • Journal Title

      Proceedings of the 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)

      Volume: - Pages: 753-754

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Porous PDMS Substrate-assisted Particle Sorting Based on Hydrodynamic Cross-flow Microfluidic Filtration2020

    • Author(s)
      Yurika Sakurai, Takeru Sato, Masumi Yamada, and Minoru Seki
    • Journal Title

      Proceedings of the 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)

      Volume: - Pages: 643-644

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laborless, Automated Microfluidic Tandem Cell Processor for Visualizing Intracellular Molecules of Mammalian Cells2019

    • Author(s)
      Mu Tinglin、Toyoda Hajime、Kimura Yuki、Yamada Masumi、Utoh Rie、Umeno Daisuke、Seki Minoru
    • Journal Title

      Analytical Chemistry

      Volume: 92 Issue: 3 Pages: 2580-2588

    • DOI

      10.1021/acs.analchem.9b04288

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hydrodynamic Microparticle Separation Mechanism Using Three-Dimensional Flow Profiles in Dual-Depth and Asymmetric Lattice-Shaped Microchannel Networks2019

    • Author(s)
      Yanai Takuma、Ouchi Takatomo、Yamada Masumi、Seki Minoru
    • Journal Title

      Micromachines

      Volume: 10 Issue: 6 Pages: 425-425

    • DOI

      10.3390/mi10060425

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] マイクロ流体デバイスを用いた微粒子材料の調製・分離技術の開発2022

    • Author(s)
      山田真澄
    • Organizer
      マイクロプロセス最前線シリーズ~新しいマイクロリアクター・マイクロデバイスの展望~
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] ポリマー微粒子を犠牲材料として用いる微粒子分用マイクロ流体システムの開発2021

    • Author(s)
      逸見るな,佐藤丈流,山田真澄,関 実
    • 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] 多孔性マトリックス統合型微粒子分用マイクロ流体デバイスの開発2021

    • Author(s)
      逸見るな,佐藤丈流,山田真澄,関 実
    • Organizer
      化学工学会秋田大会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 球状連通孔を組み込んだ微小流体デバイスを用いる微粒子の分離2021

    • Author(s)
      佐藤丈流,逸見るな,山田真澄,関 実
    • Organizer
      化学工学会 第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 多孔性基材統合型マイクロ流体デバイスにおける微粒子分離挙動のチューニング2021

    • Author(s)
      逸見るな,佐藤丈流,山田真澄,関 実
    • Organizer
      粉体工学会 第56回夏期シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 逆コロイド結晶型フィルターを組み込んだ細胞培養液交換用マイクロ流体デバイス2021

    • Author(s)
      佐藤丈流,逸見るな,山田真澄,関 実
    • Organizer
      化学とマイクロ・ナノシステム学会 第44回研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] ポーラス構造を有する流体デバイスを用いた微粒子の湿式分離2021

    • Author(s)
      櫻井優里香,山田真澄,関 実
    • Organizer
      分離技術会年会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] マルチレーン薄層マイクロ流路における血中がん細胞の捕捉挙動の評価2021

    • Author(s)
      新名菜摘,古畑 誠,山田真澄,鵜頭理恵,関 実
    • Organizer
      分離技術会年会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Microfluidic Particle Separation Device Integrated with Sponge-Like Matrix with Uniformly-sized Continuous Micropores2021

    • Author(s)
      Takeru Sato, Runa Hemmi, Masumi Yamada, and Minoru Seki
    • Organizer
      The 8th Asian Particle Technology Symposium (APT2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic Particle Sorting System Integrated with Spherically-pored PDMS Sponges as Sieving Matrices2021

    • Author(s)
      Runa Hemmi, Takeru Sato, Masumi Yamada, and Minoru Seki
    • Organizer
      The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 並列平板型マイクロ流体デバイスの深さ制御による循環がん細胞の高効率捕捉2021

    • Author(s)
      新名菜摘,古畑 誠,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第86年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 多孔性基材を統合したマイクロ流体デバイスを用いる溶液交換システム2020

    • Author(s)
      佐藤丈流, 山田真澄, 関 実
    • Organizer
      電気学会 令和2年度E部門総合研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 薄層並列型マイクロ流路を用いた血中循環がん細胞の捕捉2020

    • Author(s)
      新名菜摘,古畑 誠,山田真澄,鵜頭理恵,関 実
    • Organizer
      電気学会 令和2年度E部門総合研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 多孔性材料を組み込んだ流体デバイスにおける微粒子分離挙動の評価2020

    • Author(s)
      櫻井優里香,佐藤丈流,山田真澄,関 実
    • Organizer
      化学工学会第51回秋季大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 微小流体デバイスを用いた細胞の分離・選抜・処理システム2020

    • Author(s)
      山田真澄
    • Organizer
      大阪工業会議所「次世代医療システム産業化フォーラム2020」第4回医工連携マッチング例会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 多孔性基材を用いた微粒子分離用クロスフロー濾過デバイスの開発2020

    • Author(s)
      櫻井優里香,佐藤丈流,山田真澄,関 実
    • 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 Annual Research Report
  • [Presentation] マイクロ流体デバイスを用いた細胞分離・培養・操作システムの開発2020

    • Author(s)
      山田真澄
    • Organizer
      化学とマイクロ・ナノシステム学会第42回研究会(FT合同招待セッション)
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 血中循環がん細胞の捕捉を効率化する並列化薄層マイクロ流路2020

    • Author(s)
      新名菜摘,古畑 誠,山田真澄,鵜頭理恵,関 実
    • 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 Annual Research Report
  • [Presentation] Porous PDMS Substrate-assisted Particle Sorting Based on Hydrodynamic Cross-flow Microfluidic Filtration2020

    • Author(s)
      Yurika Sakurai, Takeru Sato, Masumi Yamada, and Minoru Seki
    • Organizer
      The 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Parallelized Microfluidic Thin Cell Trappers for Effectively Selecting Blood Circulating Tumor Cells2020

    • Author(s)
      Natsumi Shimmyo, Makoto Furuhata, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic Medium Exchanger with Micropored Fluid Drainage for Cell Culture Applications2020

    • Author(s)
      Takeru Sato, Yurika Sakurai, Masumi Yamada, and Minoru Seki
    • Organizer
      The 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 多孔性基材を統合したマイクロ流体デバイスを用いる液滴形成の制御2020

    • Author(s)
      大内貴智,山田真澄,関 実
    • Organizer
      化学工学会第85年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 並列化薄層トラップ構造を有するマイクロ流路を用いた血中がん細胞の選別2020

    • Author(s)
      新名菜摘,古畑 誠,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第85年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] PDMS-based Microporous Sieving Matrices for Size-selective Filtration of Submicrometer-sized Particles2019

    • Author(s)
      Takatomo Ouchi, Yurika Sakurai, Kayo Nakada, Masumi Yamada, and Minoru Seki
    • 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
  • [Remarks] 千葉大学 工学部共生応用化学コース バイオプロセス化学研究室

    • URL

      http://chem.tf.chiba-u.jp/gacb01/

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] バイオプロセス化学研究室HP

    • URL

      http://chem.tf.chiba-u.jp/gacb01/

    • Related Report
      2019 Annual Research Report

URL: 

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

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