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Development of single-cell mass spectrometry imaging techniques to analyze drug-cell interactions

Research Project

Project/Area Number 21H01962
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 34020:Analytical chemistry-related
Research InstitutionOsaka University

Principal Investigator

HAZAMA Hisanao  大阪大学, 大学院工学研究科, 准教授 (70437375)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2022: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2021: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords単一細胞解析 / 薬剤 / 質量分析イメージング / レーザー脱離エレクトロスプレーイオン化 / ナノ粒子
Outline of Research at the Start

レーザーイオン化を用いた質量分析イメージングは様々な分子の分布画像を非染色で同時に測定できる技術であり、創薬などへの応用が期待されているが、空間分解能が10~100 μmで細胞スケールでの観察は困難であった。レーザーの集光径を1 μm以下に小さくすると共に、気化させた試料にエレクトロスプレーで電荷を付与することで検出感度を数桁向上させ、医薬品業界における新薬や新規投薬デバイス開発の高効率化を狙う。

Outline of Final Research Achievements

Mass spectrometry imaging using laser ionization can simultaneously measure the distribution of various molecules without staining, and is expected to be applied to drug discovery, but observation at the cellular scale has been difficult due to the spatial resolution of 10 to 100 μm. In this research project, aiming at observation at the cellular scale, we developed a method to apply a charge by electrospray to a sample vaporized by laser irradiation at atmospheric pressure, and succeeded in stably detecting ions of the drugs caffeine and verapamil. We succeeded in mass spectrometry imaging of caffeine with a pixel size of 50 μm. By improving the detection sensitivity, we succeeded in detecting caffeine with a pixel size of 20 μm, demonstrating the feasibility of observation at the cellular scale.

Academic Significance and Societal Importance of the Research Achievements

質量分析イメージングでは蛍光プローブや放射性同位体による標識を行わなくても特定の分子の分布を測定できるだけでなく、予め存在が予期できない分子でも質量から分子を同定し、その分子の分布を知ることができ、極微量の分子でも検出できる。従来は、標識で検出された分子の周りでその分子と相互作用している分子が何であるかを知るには様々な制限があったが、質量分析イメージングではこのような相互作用を網羅的に解析できる可能性がある。本研究の成果を用いると薬剤分子やその代謝物の分布を高速かつ高空間分解能で測定することができるため、新規医薬品開発や薬剤投与デバイスの開発におけるブレークスルーが期待できる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 4 results) Remarks (2 results)

  • [Int'l Joint Research] National Institute on Aging/W. H. Coulter Department of Biomed. Eng.(米国)

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Increased fluorescence observation intensity during the photodynamic diagnosis of deeply located tumors by fluorescence photoswitching of protoporphyrin IX2023

    • Author(s)
      Sochi J. Ogbonna, William Y. York, Takahiro Nishimura, Hisanao Hazama, Hideo Fukuhara, Keiji Inoue, Kunio Awazu
    • Journal Title

      Journal of Biomedical Optics

      Volume: 28 Issue: 05 Pages: 055001-055001

    • DOI

      10.1117/1.jbo.28.5.055001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analyses of protoporphyrin IX fluorescence photoswitching for prolonging the photodynamic diagnosis time of deeply located tumours2023

    • Author(s)
      Ogbonna Sochi J., York William Y., Nishimura Takahiro, Hazama Hisanao, and Awazu Kunio
    • Journal Title

      Proceedings of SPIE

      Volume: 12627 Pages: 39-39

    • DOI

      10.1117/12.2670880

    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] 細胞の質量分析イメージングに向けた高繰り返しパルスレーザーイオン源の開発2022

    • Author(s)
      和田周士, 三好悠斗, 間久直, 粟津邦男
    • Journal Title

      電気学会 光・量子デバイス研究会資料

      Volume: OQD-22-001~006 Pages: 1-5

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Improvement in Ionization Efficiency Using Metal Oxide Nanoparticles in Laser Desorption/Ionization Mass Spectrometry of a Cancer Drug2021

    • Author(s)
      Kannen Hiroki, Miyoshi Yuto, Hazama Hisanao, and Awazu Kunio
    • Journal Title

      Mass Spectrometry

      Volume: 10 Issue: 1 Pages: A0099-A0099

    • DOI

      10.5702/massspectrometry.A0099

    • NAID

      130008132131

    • ISSN
      2186-5116, 2187-137X
    • Year and Date
      2021-12-23
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ガス輸送式レーザーアブレーションエレクトロスプレーイオン化を用いた大気圧質量分析イメージングにおけるヒーティングチューブの熱影響評価2024

    • Author(s)
      廣谷陸, 三好悠斗, Sendilraj Varun, 間久直
    • Organizer
      第72回質量分析総合討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒーティングチューブを用いたガス輸送式レーザーアブレーションエレクトロスプレーイオン化法による質量分析イメージングの開発2023

    • Author(s)
      廣谷陸, 間久直, 粟津邦男
    • Organizer
      第71回質量分析総合討論会
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Presentation] Analysis of the Photoproducts of the Photosensitizer, Protoporphyrin IX, used in Photodynamic Therapy of Cancers2023

    • Author(s)
      Ogbonna Sochi, Hazama Hisanao, Masuda Katsuyoshi, and Awazu Kunio
    • Organizer
      第71回質量分析総合討論会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of ambient mass spectrometry imaging using laser ablation electrospray ionization separated by gas transportation for analyses of intracellular molecules2023

    • Author(s)
      Hirotani Riku, Hazama Hisanao, and Awazu Kunio
    • Organizer
      71st ASMS Conference on Mass Spectrometry and Allied Topics
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Photobleaching and photoproducts analyses of the photosensitizers, protoporphyrin IX and protoporphyrin IX dimethyl ester, for photodynamic diagnosis/therapy of cancers2023

    • Author(s)
      Ogbonna Sochi, Hazama Hisanao, Masuda Katsuyoshi, and Awazu Kunio
    • Organizer
      71st ASMS Conference on Mass Spectrometry and Allied Topics
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analyses of protoporphyrin IX fluorescence photoswitching for prolonging the photodynamic diagnosis time of deeply located tumours2023

    • Author(s)
      Ogbonna Sochi J., York William Y., Nishimura Takahiro, Hazama Hisanao, and Awazu Kunio
    • Organizer
      European Conferences on Biomedical Optics 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the photoproducts of the photosensitizer, protoporphyrin IX, used in photodynamic therapy of cancers2023

    • Author(s)
      Ogbonna Sochi, Hazama Hisanao, Masuda Katsuyoshi, and Awazu Kunio
    • Organizer
      第71回質量分析総合討論会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of ambient mass spectrometry imaging using laser ablation electrospray ionization separated by gas transportation for analyses of intracellular molecules2023

    • Author(s)
      Riku Hirotani, Hisanao Hazama, and Kunio Awazu
    • Organizer
      71st ASMS Conference on Mass Spectrometry and Allied Topics
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞の質量分析イメージングに向けた高繰り返しパルスレーザーイオン源の開発2022

    • Author(s)
      和田周士, 三好悠斗, 間久直, 粟津邦男
    • Organizer
      電気学会 光・量子デバイス研究会
    • Related Report
      2021 Annual Research Report
  • [Remarks] 大阪大学 大学院工学研究科 間研究室ホームページ

    • URL

      http://www.see.eng.osaka-u.ac.jp/seemb/seemb/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 大阪大学 大学院工学研究科 粟津研究室ホームページ

    • URL

      http://www.see.eng.osaka-u.ac.jp/seemb/seemb/

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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