Hiruta, Yuki

写真a

Affiliation

Faculty of Science and Technology, Department of Applied Chemistry (Yagami)

Position

Assistant Professor/Senior Assistant Professor

Academic Degrees 【 Display / hide

  • 博士(工学), 慶應義塾大学理工学研究科総合デザイン工学専攻, Dissertation

 

Papers 【 Display / hide

  • Near-infrared pH responsive heptamethine cyanine platforms: Modulating the proton acceptor

    Kurutos A., Shindo Y., Hiruta Y., Oka K., Citterio D.

    Dyes and Pigments (Dyes and Pigments)  181 2020.10

    ISSN  01437208

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    © 2020 Elsevier Ltd In this report, we wish to present the rational design, synthesis, and study of optical characteristics of near-infrared (NIR) molecular probes emitting over 800 nm. The title pH sensing platforms consist of a piperazine moiety serving as a hydronium ion receptor, coupled with a rigidified symmetric heptamethine backbone. The spectrally fine-tuned response of the fluorophores was studied in both organic solvents and aqueous buffer solutions, employing combined UV–Vis and steady state fluorimetric techniques. In parallel, computational approach and optical spectroscopy were employed aiming to ascribe the origin of spectral behavior of the amino-substituted heptamethines. Herein, we also investigated the halochromic effect of the differently substituted piperazines on the spectral properties of the NIR cyanine dyes. Under acidic conditions, the protonation of the piperazine moiety promoted a gradual bathochromic shift in the absorption spectra. The Δλ between the neutral and the protonated forms are indirectly related to the modifications applied to the proton acceptor. The calculated pKa values (5.13–7.06) were found to be dependent on the dye chemical structure. A good linear correlation was established between the pKa of the newly synthesized dyes and that of the reported piperazine moieties. This aspect allows the future expansion of the current facile strategy since sensing chromophores with predicted pH response could readily be designed based on pKa databases for substituted piperazine derivatives. A detailed literature study along with NMR and computational methods were found to be in agreement with our assumption, that both nitrogen atoms of the 1,4-disubstituted amine are involved in the sensing process. The covered pKa range allows us to recommend the title fluorophores as promising potential candidates for qualitative analysis of biological samples. A cytotoxicity study by the MTT assay showed that the NIR dyes are safe and applicable for bioanalytical purposes at dye concentrations up to 10 μM. Fluorescence imaging and cellular applications, including staining and visualization of HeLa cervical cancer cells was successfully demonstrated.

  • All-printed semiquantitative paper-based analytical devices relying on QR code array readout

    Katoh A., Maejima K., Hiruta Y., Citterio D.

    The Analyst (The Analyst)  145 ( 18 ) 6071 - 6078 2020.09

    ISSN  0003-2654

     View Summary

    The wide spread of smartphones and QR codes for various end-user applications has had an impact beyond traditional fields of use, recently also reaching point-of-care testing (POCT). This work presents the integration of QR code recognition into paper-based analytical devices (PADs) with "distance-based" colorimetric signalling, resulting in semiquantitative readout fully relying on straightforward barcode reader solutions. PADs consist of an array of QR codes arranged in series inside a paperfluidic channel. A mask dye concept has been developed, which enables utilisation of colour changing indicators by initially hiding QR codes. The colour change of the indicator induced by the presence of an analyte of interest results in gradual unmasking of QR codes, which become recognisable by the smartphone barcode reader app. To reproducibly fabricate devices, all fabrication steps were performed by commercial desktop solid ink and inkjet printing. The QR code masking function was optimised by controlling the amount of printed mask dye through adjusting the opacity of printing patterns during the inkjet deposition process. For proof-of-concept, a model assay in the form of colorimetric copper ion (Cu2+) detection in the concentration range of 0.4 mM to 3.2 mM was evaluated. Consistent results independent of the smartphone model and environmental light condition were achieved with a free barcode reader app. To the best of our knowledge, this work is the first demonstration of a semiquantitative assay approach fully relying on QR code readout without digital colour analysis, customised app or hardware modification.

  • Text-Displaying Semiquantitative Competitive Lateral Flow Immunoassay Relying on Inkjet-Printed Patterns

    Misawa K., Yamamoto T., Hiruta Y., Yamazaki H., Citterio D.

    ACS Sensors (ACS Sensors)  5 ( 7 ) 2076 - 2085 2020.07

    ISSN  2379-3694

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    Copyright © 2020 American Chemical Society. This work describes a colorimetric signaling approach for competitive lateral flow immunoassays (LFIAs) enabling sensitive and semiquantitative direct visual result readout in the form of "text", demonstrated on the example of 8-hydroxy-2′-deoxyguanosine (8-OHdG) detection. The distinctive feature of the developed text-displaying LFIA (TD-LFIA) is the test zone system consisting of a combination of two types of inkjet-deposited capture molecules referred to as "mask antigen"and "text antibody", allowing for sensitive turn-on signaling as opposed to the inverse response of conventional competitive LFIAs. The user operation is limited to sample application, followed by direct reading of assay results written in text after approximately 10 min. TD-LFIAs enabled the visual detection of 8-OHdG at concentrations down to 3 ng/mL, which is a 2-3 orders of magnitude lower visual detection limit than that achieved with the corresponding conventional design and is comparable to the existing LFIAs relying on external signal readout equipment. Highly reproducible observer-independent assay performance was confirmed, and the result interpretation is not influenced by sample color and readout timing. Making use of customizable threshold settings for text appearance, a device for semiquantitative assays was developed and successfully applied to the detection of 8-OHdG at four concentration levels (trace, low, medium, and high) in 54 human urine samples within the clinically relevant concentration range. The sensitive and intuitive signaling method of the developed system offers great potential for an alternative competitive LFIA platform suitable for real-world point-of-care testing applications.

  • Thread-Based Bioluminescent Sensor for Detecting Multiple Antibodies in a Single Drop of Whole Blood

    Tomimuro K., Tenda K., Ni Y., Hiruta Y., Merkx M., Citterio D.

    ACS Sensors (ACS Sensors)  5 ( 6 ) 1786 - 1794 2020.06

    ISSN  2379-3694

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    Copyright © 2020 American Chemical Society. Antibodies are important biomarkers in clinical diagnostics in addition to being increasingly used for therapeutic purposes. Although numerous methods for their detection and quantification exist, they predominantly require benchtop instruments operated by specialists. To enable the detection of antibodies at point-of-care (POC), the development of simple and rapid assay methods independent of laboratory equipment is of high relevance. In this study, we demonstrate microfluidic thread-based analytical devices (μTADs) as a new platform for antibody detection by means of bioluminescence resonance energy-transfer (BRET) switching sensor proteins. The devices consist of vertically assembled layers including a blood separation membrane and a plastic film with a sewn-in cotton thread, onto which the BRET sensor proteins together with the substrate furimazine have been predeposited. In contrast to intensity-based signaling, the BRET mechanism enables time-independent, ratiometric readout of bioluminescence signals with a digital camera in a darkroom or a smartphone camera with a 3D-printed lens adapter. The device design allows spatially separated deposition of multiple bioluminescent proteins on a single sewn thread, enabling quantification of multiple antibodies in 5 μL of whole blood within 5 min. The bioluminescence response is independent of the applied sample volume within the range of 5-15 μL. Therefore, μTADs in combination with BRET-based sensor proteins represent user-friendly analytical tools for POC quantification of antibodies without any laboratory equipment in a finger prick (5 μL) of whole blood.

  • Metal-Free Colorimetric Detection of Pyrophosphate Ions by Inhibitive Nanozymatic Carbon Dots

    Chen C.Y., Tan Y.Z., Hsieh P.H., Wang C.M., Shibata H., Maejima K., Wang T.Y., Hiruta Y., Citterio D., Liao W.S.

    ACS sensors (ACS sensors)  5 ( 5 ) 1314 - 1324 2020.05

    ISSN  2379-3694

     View Summary

    The pyrophosphate ion (P2O74-, PPi) plays a critical role in various biological processes and acts as an essential indicator for physiological mechanism investigations and disease control monitoring. However, most of the currently available approaches for PPi species detection for practical usage still lack appropriate indicator generation, straightforward detection requirements, and operation convenience. In this study, a highly sensitive and selective PPi detection approach via the use of nanozymatic carbon dots (CDs) is introduced. This strategy eliminates the common need for metal ions in the detection process, where a direct indicator-PPi interaction is adopted to provide straightforward signal reports, and importantly, through a green indicator preparation. The preparation of this nanozymatic CDs' indicator utilizes an aqueous solution refluxing, employing galactose and histidine as the precursor materials. The mild conditions of the solution refluxing produce fluorescent CDs exhibiting peroxidase-mimic properties, which can catalyze the o-phenylenediamine oxidation under the presence of H2O2. The introduction of PPi species, interestingly, inhibits this process very efficiently, the extent of which can be colorimetrically monitored by the generated yellow product 2,3-diaminophenazine. Spectroscopic results point to CD surface functional groups' selective binding toward PPi species, which severely interferes with the electron transfer process in the enzymatic catalysis. Relying on this CD peroxidase-mimetic property inhibition, sensitive and selective recognition of PPi reaches a detection limit of 4.29 nM, enabling practical usage in complex matrixes. Owing to the superior compatibility and high stability of nanozymatic CDs, they can also be inkjet-printed on paper-based devices to create a portable and convenient platform for PPi detection. Both the solution and the paper-device-based selective recognitions confirm this unique and robust metal-free inhibitive PPi detection, which is supported by a convenient green preparation of nanozymatic CDs.

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • 近赤外蛍光マグネシウムイオンプローブの開発と マルチカラー細胞イメージングへの応用

    蛭田勇樹

    日本分析化学会第68年会, 2019.09, Oral Presentation(general)

  • pH-response tunable mixed-charged polymers for reversible adsorption and desorption of proteins

    ACS Fall 2019 National Meeting & Exposition, 2019.08, Oral Presentation(general)

  • Development of temperature-responsive polymer materials for cancer therapy and imaging

    The 2019 Controlled Release Society Annual Meeting & Exposition, 2019.07, Poster (general)

  • pH-Responsive mixed-charge polymer for weak acidic tumorous environment selective cellular uptake

    蛭田勇樹

    第68回高分子学会年次大会, 2019.05, Oral Presentation(general)

  • Alkali resistant calcium carbonate porous particles for high-performance liquid chromatography

    Yuki Hiruta

    The 99th CSJ Annual Meeting, 2019.03, Oral Presentation(general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Development of polymer caged luciferin enabling spatiotemporal trans-scale imaging

    2019.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 蛭田 勇樹, Grant-in-Aid for Scientific Research on Innovative Areas, Principal Investigator

  • Development of tumor self-accumulating functionalized theranostics nanoplatform

    2019.04
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 蛭田 勇樹, Grant-in-Aid for Early-Career Scientists , Principal Investigator

  • 血中抗体医薬品のPOC分析を可能にするマイクロ流体糸基板センサー

    2018.04
    -
    2021.03

    チッテリオ ダニエル, Co-investigator

  • Development of dual pH-responsive drug delivery career by the logical design of polymer

    2015.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 蛭田 勇樹, Grant-in-Aid for Young Scientists (B), Principal Investigator

     View Summary

    We report a polymeric micelle drug delivery system, which enables selective intracellular uptake with external thermal stimulation, and effective release of a drug at internal acidic endosomal pH. We developed dual temperature- and pH-responsive polymeric micelle encapsulated anti-cancer agent, doxorubicin (DOX). The resultant micelle exhibited a temperature-dependent phase transition at a temperature slightly higher than body temperature, and intracellular uptake of encapsulated DOX was accelerated above phase transition temperature. The cytotoxicity of doxorubicin (DOX)-loaded dual temperature- and pH-responsive micelles against human cervical cancer HeLa cells was significantly greater at 42 °C than at 37 °C, This proof-of-concept synergistic two-step delivery system with enhanced intracellular uptake upon external thermal stimulation and rapid release of DOX at internal acidic endosomal pH was effective against tumor cells in vitro.

  • LAT1選択的蛍光ポリマープローブの創製とがん可視化への応用

    2015.01
    -
    2015.12

    No Setting, Principal Investigator

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Awards 【 Display / hide

  • Award for Encouragement of Research in Analytical Chemistry

    2020.08, The Japan Society of Analytical Chemistry, Development and application of bioimaging probes based on precision molecular design

    Type of Award: Awards of National Conference, Council and Symposium

  • Award for Encouragement of Research in Polymer Science

    Development of stimuli-responsive polymer materials for application to medical analysis, 2020.05, 公益社団法人高分子学会, 医療分析への応用を志向した刺激応答性高分子材料の開発

    Type of Award: Awards of National Conference, Council and Symposium

  • 日本化学会第99春季年会 優秀講演賞(学術)

    2019.04, 公益財団法人 日本化学会

    Type of Award: Awards of National Conference, Council and Symposium

  • 平成29年度物理系薬学部会奨励賞

    2017.03, 日本薬学会 物理系薬学部会, 診断技術への応用を目指したスマートポリマープローブの精密設計

  • 平成27年度慶應義塾大学薬学部長賞(研究)

    2016.03

    Type of Award: Keio commendation etc.

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Courses Taught 【 Display / hide

  • SEMINAR IN APPLIED CHEMISTRY

    2020

  • PRACTICAL INSTRUMENTAL ANALYSIS

    2020

  • NANO SCALE SCIENCE JOINT SEMINAR

    2020

  • MATERIAL DESIGN SCIENCE JOINT SEMINAR

    2020

  • LABORATORY IN SCIENCE

    2020

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Memberships in Academic Societies 【 Display / hide

  • クロマトグラフィー科学会会員, 

    2016.01
    -
    Present
  • 高分子学会会員, 

    2016.01
    -
    Present
  • 日本DDS学会会員, 

    2014.04
    -
    Present
  • 日本薬学会会員, 

    2014.01
    -
    Present
  • 日本化学会会員, 

    2010.01
    -
    Present

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Committee Experiences 【 Display / hide

  • 2018.04
    -
    Present

    代議員, 日本分析化学会

  • 2017.01
    -
    2018.12

    関東支部幹事, 日本分析化学会