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Development of Contactless and Label-free Measurement of Membrane Potential Using Dual-Comb Spectroscopy

Research Project

Project/Area Number 21K19913
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionThe University of Tokushima

Principal Investigator

TAKANARI Hiroki  徳島大学, ポストLEDフォトニクス研究所, 准教授 (70723253)

Co-Investigator(Kenkyū-buntansha) 江本 顕雄  徳島大学, ポストLEDフォトニクス研究所, 特任准教授 (80509662)
吉井 一倫  徳島大学, ポストLEDフォトニクス研究所, 特任准教授 (90582627)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywordsデュアルコム干渉計 / 活動電位 / 細胞膜電位 / 非標識測定 / 非標識イメージング / デュアルコム分光 / ITO薄膜 / 電界 / 光学計測 / デュアルコム分光法 / ラベルフリー
Outline of Research at the Start

細胞膜に生じる80 mVから90 mVに及ぶ電位変化は、細胞膜の誘電率テンソルに変化を及ぼすと考えられる。この誘電率のわずかな変化を、精密測定が可能なデュアルコム分光法によって捉える事を提案する。デュアルコム分光法は物質の光学特性の超精密測定を高速で行うことができる手法であり、ナノ秒単位で変化する細胞の活動電位を捉える事ができる可能性がある。そこで本研究では、光周波数コムを細胞膜や細胞膜を模した非生体サンプルに照射し、サンプルに加えた電場によって生じる光学特性の変化を精密に測定・分析する。

Outline of Final Research Achievements

Cells function physiologically via electrical activity. Contact measurement using electrodes and optical mapping using voltage-sensitive dyes are commonly used to measure the electrical activity of the cells. However, these techniques can only be used on single cells or excised organs and are not clinically applicable. We constructed a dual-comb interferometer that transmits an optical frequency comb through a sample and analyzes the interference waves with a reference optical frequency comb. As a preliminary step of the in vivo measurement, we prepared a sample with conductive thin films coated on both sides of glass to imitate a cell membrane, and applied a potential difference between the conductive films to measure the interference wave with the dual-comb interferometer. This experiment demonstrated the possibility of contactless, label-free measurement of potential changes inside and outside the cytoplasmic membranes.

Academic Significance and Societal Importance of the Research Achievements

これまで細胞膜電位の変化は電極による接触計測や、電位感受性色素による光学マッピングによって達成されてきたが、前者は単一細胞にしか応用できず、後者は色素の毒性のため生体に直接用いることができない。このため、人体で細胞の電気的活動を直接知る方法が存在しない。我々は非生体試料ではあるが細胞膜を模したサンプルを作成し、2枚の薄膜間で電位差を生じた時に透過光の微細な位相変化が生じることを示した。今後、反射光学系での検証など改良を必要とするが、我々の研究成果が生体で応用されれば、神経や筋肉など多くの細胞の電気的活動を非接触・非標識で計測出来るようになる可能性がある。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (23 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (14 results) (of which Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] UMC Utrecht(オランダ)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Elastin is responsible for the rigidity of the ligament under shear and rotational stress: a mathematical simulation study2023

    • Author(s)
      Naya Yuki、Takanari Hiroki
    • Journal Title

      Journal of Orthopaedic Surgery and Research

      Volume: 18 Issue: 1 Pages: 310-310

    • DOI

      10.1186/s13018-023-03794-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of miR-143 and miR-146 in Risk Evaluation of Coronary Artery Diseases in Autopsied Samples2023

    • Author(s)
      Tie Jian、Takanari Hiroki、Ota Koya、Okuda Takahisa
    • Journal Title

      Genes

      Volume: 14 Issue: 2 Pages: 471-471

    • DOI

      10.3390/genes14020471

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case Report of Acute Cardiac Tamponade Creation in a Macaque: Echo-Guided Catheter Manipulation to Perforate Coronary Artery2023

    • Author(s)
      Takanari Hiroki、Okuyama Minami W、Kuroki Kohji、Kondo Hidekazu、Kira Shintaro、Miura Masahiro、Takahashi Naohiko、Okuda Takahisa
    • Journal Title

      Yonago Acta Medica

      Volume: 66 Issue: 1 Pages: 192-195

    • DOI

      10.33160/yam.2023.02.022

    • ISSN
      0513-5710, 1346-8049
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessment of skin inflammation using near-infrared Raman spectroscopy combined with artificial intelligence analysis in an animal model2022

    • Author(s)
      Kanemura Y, Kanazawa M, Hashimoto S, Hayashi Y, Fujiwara E, Suzuki A, Ishii T, Goto M, Nozaki H, Inoue T, Takanari H
    • Journal Title

      Analyst

      Volume: -

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantitative Analysis of the Cytoskeleton’s Role in Inward Rectifier KIR2.1 Forward and Backward Trafficking2022

    • Author(s)
      Li Encan、Loen Vera、van Ham Willem B.、Kool Willy、van der Heyden Marcel A. G.、Takanari Hiroki
    • Journal Title

      Frontiers in Physiology

      Volume: 12 Pages: 812572-812572

    • DOI

      10.3389/fphys.2021.812572

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Rotors anchored by refractory islands drive torsades de pointes in an experimental model of electrical storm2022

    • Author(s)
      Yamazaki M, Makita N, Tsuji Y, et al.
    • Journal Title

      Heart Rhythm

      Volume: 19 Issue: 2 Pages: 318-329

    • DOI

      10.1016/j.hrthm.2021.10.012

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Potential of a new photothermal therapy against amyloid-β protein based on nanodaiamonds.2023

    • Author(s)
      Shintani M, Yanagiya S, Takanari H.
    • Organizer
      The 100th. Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Label-free voltage measurement by dual-comb interferometry: a fundamental study for label-free imaging of action potentials.2023

    • Author(s)
      Araoka S, Takanari H, Mitsumoto R, Emoto A, Yoshii K.
    • Organizer
      The 100th. Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Assessment of collagen fiber orientation in alcoholic liver disease using polarization-resolved second harmonic generation microscopy.2023

    • Author(s)
      Oshikata H, Matsuzaki S, Hase E, Takanari H, Kimura S, Tsuneyama K.
    • Organizer
      The 100th. Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] The mechanisms of intracellular Ca2+ increase by Timosaponin AIII in HeLa cells.2023

    • Author(s)
      Takahashi R, Takanari H, Terabayashi T, Ishizaki T.
    • Organizer
      The 100th. Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Diagnosis of cardiac amyloidosis using Raman spectroscopy.2023

    • Author(s)
      Yoshimoto M, Honda T, Takanari H,Yanagiya S, Miki H.
    • Organizer
      The 100th. Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] SREBP1-mediated GJA5 expression in cholesterol excess and depletion.2023

    • Author(s)
      Kanada N, Takanari H.
    • Organizer
      The 100th. Aniversary Annual Meeting of the Physiological Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Verification of a new targeted therapy against amyloid-β using nanodaiamonds.2022

    • Author(s)
      Shintani M, Yanagiya S, Takanari H.
    • Organizer
      The 60th. Annual Meeting of the Biophysical Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Label-free detection of membrane potential using dual-comb interferometry.2022

    • Author(s)
      Araoka S, Takashima Y, Naoi Y, Emoto A, Yoshii K, Mitsumoto R, Takanari H.
    • Organizer
      The 60th. Annual Meeting of the Biophysical Society of Japan
    • Related Report
      2022 Annual Research Report
  • [Presentation] Verification of mechanical load on ligament by mathematical model based on multiphoton microscope images2022

    • Author(s)
      納谷友希、髙成広起
    • Organizer
      第99回日本生理学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 光分光法および画像解析を組み合わせた食品の非破壊分析2022

    • Author(s)
      鈴木絢子、納谷友希、金村洋平、髙成広起、井上高教
    • Organizer
      日本農芸化学会2022年度大会
    • Related Report
      2021 Research-status Report
  • [Presentation] フォトポリマーの重合時交差拡散に伴う分子配向拡散様式の調査2022

    • Author(s)
      丸山慧、江本顕雄
    • Organizer
      レーザー学会学術講演会第42回年次大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 皮膚ケラチノサイトの紫外線に対する光応答2022

    • Author(s)
      金村洋平、髙成広起
    • Organizer
      第30回日本病態生理学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 数理シミュレーションモデルを用いた靱帯主要構成要素における力学的応答の検証2022

    • Author(s)
      納谷友希、髙成広起
    • Organizer
      第30回日本病態生理学会大会
    • Related Report
      2021 Research-status Report
  • [Presentation] フォトポリマーの重合時交差拡散を利用したオンデマンドのマイクロ流路デバイス作成技術2021

    • Author(s)
      江本顕雄
    • Organizer
      第172回ラドテック研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Remarks] 画像処理・画像解析による医療支援 内視鏡と画像強調解析における画像センサの役割 (1)

    • URL

      http://sensait.jp/21189/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 画像処理・画像解析による医療支援 内視鏡と画像強調解析における画像センサの役割(2)

    • URL

      http://sensait.jp/21193/

    • Related Report
      2022 Annual Research Report

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Published: 2021-07-13   Modified: 2024-01-30  

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