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Detection method for 10-100nm nanofluidic engineering and application to single cell proteomics

Research Project

Project/Area Number 19H00850
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 28:Nano/micro science and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Mawatari Kazuma  東京大学, 大学院工学系研究科(工学部), 准教授 (60415974)

Co-Investigator(Kenkyū-buntansha) 森川 響二朗  東京大学, 大学院工学系研究科(工学部), 助教 (20796437)
Le ThuHacHuong  東京大学, 大学院工学系研究科(工学部), 講師 (60752144)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2021: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
Fiscal Year 2020: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywordsナノ流路 / 光回折 / 分析化学 / 単一細胞 / クロマトグラフィ / 非標識検出 / 超高感度 / ナノフルイディクス / 極限液相空間 / 超高感度検出 / 溶液物性 / 可算個分子 / 光らない分子 / プロテオミクス / 光熱変換 / 非蛍光性分子 / ナノ流体工学
Outline of Research at the Start

10-100nmナノ流路を利用するナノ流体工学は、超微小・超高比界面積を利用した極限化学操作を可能として、単一細胞や単一分子レベルの極限分析など化学やバイオへ革新的ツールをもたらすと期待され、学術・技術両面から重要である。しかし、最も重要である検出法、特に光らない分子(非蛍光性分子)を検出する汎用的な検出法が不可欠であるが、10-100nmの超微小空間では蛍光法に限定され、非蛍光性分子の検出は困難であり、ナノ流体工学発展の障壁となっていた。そこで、本申請では光回折を利用する新しい方法論を展開して、10-100nm空間での単一分子検出法を実現して、細胞生物学でのニーズが高い単一細胞プロテオミクスへ応用する。

Outline of Final Research Achievements

Microfluidic engineering is widely used in chemistry, biology, and medicine and is now moving to an extreme size space, nanoscale. However, the detection is extremely difficult due to the small size. In this study, new detection method, photothermal optical diffraction (POD) was created for the space, which is based on the popular detection principle of light absorption. The proposed principles were confirmed, and the detection system was optimized. As a result, ultrasensitive detection (10 molecules) was realized in a 70 nm nanochannel. Then, separation analysis was integrated into the 70 nm nanochannels. The sampling size is fL scale which is much smaller than single cell volume, and the established technology will be a platform for single cell analysis. Overall, ultrasensitive detection and separation method in extreme size region below 100 nm were realized for the first time.

Academic Significance and Societal Importance of the Research Achievements

コロナウィルスなどナノレベルの物質を1個で分析するための極限分析手法が求められている。しかし、フラスコやビーカーなど従来のツールでは大きすぎて高感度分析は困難である。そこで、本研究では液体を扱う容器としては極限的に小さい10-100nm空間(ナノチャネル)で分析するプラットフォームを構築した。光吸収・発熱を利用して分子を10分子レベルで検出するPOD法を実現し、最小70nm空間での極限分析が可能となり、新しい学術ツールを創成できた。今後、本成果を用いて、ウィルス一個の検出やがんの原因であるエキソソーム(ナノ物質)1個を分析するツールになると期待され、医学や生物学に大きな貢献が期待できる。

Report

(5 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report
  • Research Products

    (16 results)

All 2022 2021 2020 2019

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Nanofluidic optical diffraction interferometry for detection and classification of individual nanoparticles in a nanochannel2022

    • Author(s)
      Yoshiyuki Tsuyama and Kazuma Mawatari
    • Journal Title

      Microfluidics and Nanofluidics

      Volume: 26 Issue: 8 Pages: 63-63

    • DOI

      10.1007/s10404-022-02562-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integration of sequential analytical processes into sub-100 nm channels: Volumetric sampling, chromatographic separation, and label-free molecule detection2021

    • Author(s)
      Yoshiyuki Tsuyama, Kyojiro Morikawa, and Kazuma Mawatari
    • Journal Title

      Nanoscale

      Volume: 13 Issue: 19 Pages: 8855-8863

    • DOI

      10.1039/d0nr08385b

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Concentration Determination at Countable Molecular Level in Nanofluidics by Solvent-enhanced Photothermal Optical Diffraction2020

    • Author(s)
      Y. Tsuyama, K. Morikawa, and K. Mawatari
    • Journal Title

      Analytical Chemistry

      Volume: 92 Issue: 21 Pages: 14366-14372

    • DOI

      10.1021/acs.analchem.0c02024

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Nanochannel Chromatography and Photothermal Optical Diffraction: Femtoliter Sample Separation and Label-free Zeptomole Detection2020

    • Author(s)
      Y. Tsuyama, K. Morikawa, and K. Mawatari
    • Journal Title

      Journal of Chromatography A

      Volume: 1624 Pages: 461265-461265

    • DOI

      10.1016/j.chroma.2020.461265

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Detection and Characterization of Individual Nanoparticles in a Liquid by Photothermal Optical Diffraction and Nanofluidics2020

    • Author(s)
      Y. Tsuyama and K. Mawatari
    • Journal Title

      Analytical Chemistry

      Volume: 92 Issue: 4 Pages: 3434-3439

    • DOI

      10.1021/acs.analchem.9b05554

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
  • [Journal Article] Nonfluorescent Molecule Detection in 102 nm Nanofluidic Channels by Photothermal Optical Diffraction2019

    • Author(s)
      Yoshiyuki Tsuyama and Kazuma Mawatari
    • Journal Title

      Analytical Chemistry

      Volume: 15 Issue: 15 Pages: 9741-9746

    • DOI

      10.1021/acs.analchem.9b01334

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] ナノ流体工学で明らかにする10-100nm空間の溶液物性と構造2022

    • Author(s)
      馬渡和真
    • Organizer
      液体・非晶質研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Dual measurement of optical absorption and scattering of single nanoparticles in flow by nanofluidic optical diffraction2021

    • Author(s)
      Yoshiyuki Tsuyama and Kazuma Mawatari
    • Organizer
      Micro Total Analysis System 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nanofluidic diffractometry for 10-100 nm nanofluidic science and analytical chemistry2021

    • Author(s)
      Kazuma Mawatari
    • Organizer
      The 23rd Annual Meeting of the China Association for Science and Technology
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Solvent -enhanced Photothermal Molecule Detection Method for Nanofluidics and Its Application to Femtoliter Normal-phase Chromatography2020

    • Author(s)
      Y. Tsuyama and K. Mawatari
    • Organizer
      MircoTAS2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイクロ・ナノ流体デバイスの学術とデバイス応用2020

    • Author(s)
      馬渡和真
    • Organizer
      次世代医療技術研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マイクロ・ナノ流体デバイスの極限を目指して2020

    • Author(s)
      馬渡和真
    • Organizer
      日本分析化学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] マイクロフルイディクスによる分析・診断技術の革新2020

    • Author(s)
      馬渡和真
    • Organizer
      Dermatology学術講演会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] ltrasensitive non-label detection method for nanofluidics using nanochannel optical diffraction2019

    • Author(s)
      Kazuma Mawatari
    • Organizer
      Beijing Conference and Exhibition on Instrumental Analysis,
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Patent(Industrial Property Rights)] 微粒子計測装置及び微粒子計測方法2021

    • Inventor(s)
      津山慶之、馬渡和真
    • Industrial Property Rights Holder
      津山慶之、馬渡和真
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-126164
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 光熱変換分光装置及び微量検体検出方法2019

    • Inventor(s)
      馬渡 和真
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-113575
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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