Details of a Researcher

Hiruta, Yuki

写真a

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

Position: Assistant Professor/Senior Assistant Professor

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Career 【 Display / hide 】

2010.04

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2011.03

Keio University, Graduate School of Science and Technology, Assistant Professor
2011.04

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2013.03

Japan Society for the Promition of Science, Research Fellowship for Young Scientists (DC2)
2013.04

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2017.03

Keio University, Faculty of Pharmacy, Assistant Professor
2017.04

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Present

Keio University, Faculty of Science and Technology, Assistant Professor

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Academic Background 【 Display / hide 】

2004.04

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2008.03

Keio University, Faculty of Science and Technology, Department of Applied Chemistry

University, Graduated
2008.04

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2010.03

Keio University, Graduate School of Science and Technology, School of Integrated Design Engineering

Graduate School, Completed, Master's course
2010.04

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2013.03

Keio University, Graduate School of Science and Technology, School of Integrated Design Engineering

Graduate School, Completed, Doctoral course

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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

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Books 【 Display / hide 】

Development of Near-Infrared Fluorescent Mg<sup>2+</sup> Probe and Application to Multicolor Imaging of Intracellular Signals

Shindo Y., Ikeda Y., Hiruta Y., Citterio D., Oka K., Methods in Molecular Biology, 2021

　View Summary

Recent extensive studies revealed that the intracellular concentration of magnesium ions (Mg2+) is one of the important factors to regulate cellular functions. To evaluate the impact of Mg2+ concentration changes on intracellular signals or events, simultaneous imaging of Mg2+ with those phenomena is a powerful technique. The present protocol describes the synthesis and evaluation of near-infrared (NIR) fluorescent Mg2+-selective probes, named KMG-500 series, and the application to simultaneous imaging of the corresponding intracellular signal transductions and molecular events. The present protocol for multicolor imaging using fluorescent probes in the NIR and visible ranges is highly useful to reveal how multiple molecular events are correlated each other in each single cell.

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Papers 【 Display / hide 】

Quantitative evaluation of reversed-phase packing material based on calcium carbonate microspheres modified with an alternating copolymer

Kaizu K., Mochida M., Imai H., Citterio D., Hiruta Y.

Journal of Chromatography A （Journal of Chromatography A) 1677 2022.08

ISSN 00219673

　View Summary

Considering the vulnerability of silica gel to alkaline mobile phases, a highly alkaline stable stationary phase for HPLC is required to separate basic compounds with high separation efficiency. To address this issue, we have developed a high alkaline stable packing material (CaCO3-PMAcO) based on mesoporous calcium carbonate microspheres modified with poly(maleic acid-alt-1-octadecene). In this study, we report further investigation of the separation performance of CaCO3-PMAcO column by systematically evaluating the effects of particle size and chromatographic conditions. Based on the theory of the van Deemter equation, the separation efficiency was related to the size of CaCO3-PMAcO particles (2.9 – 5.7 µm). The evaluation of thermodynamics of retention by changing the column temperature from 20 °C to 45 °C implied that the retention mode was dominated by hydrophobic interaction associated with the exothermic enthalpy changes (-11.1 to -12.5 kJ/mol). The results of column selectivity tests revealed that the CaCO3-PMAcO column had hydrophobic selectivity comparable to C18 silica gel columns (αP/B; CaCO3-PMAcO column: 1.53, C18 column: 1.69), and higher shape/steric selectivity (αTri/Ter; CaCO3-PMAcO column: 1.56, C18 column: 0.955). In practice, the CaCO3-PMAcO column could be applied to the separation of not only alkylbenzenes and polycyclic aromatic hydrocarbons, but also to basic tricyclic antidepressants by using an alkaline mobile phase (pH 12).
- Access to Document (DOI)
Poly(N-isopropylacrylamide)-based temperature- and pH-responsive polymer materials for application in biomedical fields

Hiruta Yuki

POLYMER JOURNAL 2022.08

ISSN 0032-3896
- Access to Document (DOI)
Organelle-selective near-infrared fluorescent probes for intracellular microenvironment labeling

Kurutos Atanas, Shindo Yutaka, Hiruta Yuki, Oka Kotaro, Citterio Daniel

DYES AND PIGMENTS （Dyes and Pigments) 204 2022.08

ISSN 0143-7208

　View Summary

The design, synthesis, and bio-applicability of a series of 8 near-infrared (NIR) molecular probes with tunable hydrophilic/hydrophobic properties are described in this paper. The title dyes comprise of symmetric heptamethine cyanines with various N-quaternary heterocyclic moieties including indole, benzo[e]indol, benzothiazole and naphtho[1,2-d]thiazole, along with an extra positive charge in close proximity to the polymethine backbone. Combined UV–Vis and spectrofluorimetric techniques in both organic and aqueous-buffered solutions were employed to investigate the optical properties of the NIR chromophores. Two of the fluorophores emerged remarkable fluorescence quantum yield (Φ = 0.083), while their brightness was found up to 3-fold that of the FDA approved Indocyanine green – ICG (Φ = 0.027). What is more, two of the dyes appear to outperform the later clinical benchmark fluorophore in terms of photostability. While the ICG was completely faded after 1 h of constant irradiation, nearly 70% of the original emission signal could be observed for one of the novel molecular probes. The log Pow values determined by a combination of HPLC and UV–Vis (partition between 1-octanol/water) cover a relatively large range, from −2.14 up to 7.92. Investigation on the cytotoxicity by means of the MTT assay revealed, that present dyes are suitable for bioanalytical purposes and are safe to use. This paper also includes fluorescence imaging and cellular applications, such as labeling of HeLa cervical cancer cells. The results from the confocal microscopy reveal the superior staining capability of current heptamethines since they show significantly brighter signal than the commercial ICG probe. An organelle-selective fluorescent staining was achieved depending on the dye chemical structure. Co-localization within the intracellular microenvironment (linear or granular - cytosol, mitochondria, lysosome, endoplasmatic reticulum or Golgi apparatus) was confirmed without interference, employing several conventional organelle dye trackers. To the best of our knowledge, heptamethine dyes represent the first example of a series NIR emitting probes, that exhibit rational structural modifications aiming to fine-tune the hydrophilic/hydrophobic properties furnishing organelle-targeted staining.
- Access to Document (DOI)
Feasibility of Using Poly[oligo(ethylene glycol) Methyl Ether Methacrylate] as Tumor-Targeted Carriers of Diagnostic Drugs

Sano Kohei, Umemoto Koki, Miura Haruka, Ohno Satoshi, Iwata Kyohei, Kawakami Rin, Munekane Masayuki, Yamasaki Toshihide, Citterio Daniel, Hiruta Yuki, Mukai Takahiro

ACS APPLIED POLYMER MATERIALS 2022.06

ISSN 2637-6105
- Access to Document (DOI)
A Series of Furimazine Derivatives for Sustained Live-Cell Bioluminescence Imaging and Application to the Monitoring of Myogenesis at the Single-Cell Level

Orioka M., Eguchi M., Mizui Y., Ikeda Y., Sakama A., Li Q., Yoshimura H., Ozawa T., Citterio D., Hiruta Y.

Bioconjugate Chemistry （Bioconjugate Chemistry) 33 （ 3 ） 496 - 504 2022.03

ISSN 10431802

　View Summary

Bioluminescence (BL) imaging, which utilizes light emitted through the enzymatic reaction of luciferase oxidizing its substrate luciferin, enables sensitive and noninvasive monitoring of life phenomena. Herein, we developed a series of caged furimazine (FMZ) derivatives by introducing a protective group at the C-3 position and a hydroxy group at the C-6 phenyl ring to realize long-term live-cell BL imaging based on the NanoLuc (NLuc)/NanoKAZ (NKAZ)-FMZ system. The membrane permeability and cytotoxicity of the substrates were evaluated and related to their hydrophobicity. Among the series, the derivative with the bulkiest protective group (adamantanecarbonyl group) and a hydroxy substituent (named Ad-FMZ-OH) showed significantly prolonged and constant BL signal in cells expressing NLuc compared to the native FMZ substrate. This derivative enabled continuous BL imaging at the single-cell level for 24 h. Furthermore, we applied Ad-FMZ-OH to BL imaging of myocyte fusion and succeeded in the consecutive and sensitive monitoring at a single-cell level over a day. In summary, NLuc/NKAZ-caged FMZ derivatives have the potential to be applied to live-cell BL imaging of various life phenomena that require long-term observation.
- Access to Document (DOI)

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

Optical imaging technology for manipulating and observing intracellular magnesium ions

Hiruta, Yūki

福澤諭吉記念慶應義塾学事振興基金事業報告集（福澤基金運営委員会) 2020
Development of dual pH-responsive drug delivery career by the logical design of polymer

Hiruta, Yuki

科学研究費補助金研究成果報告書 2016
The development of environmentally responsive fluorescence polymer probes for visualizing pathological cells

Hiruta, Yuki

科学研究費補助金研究成果報告書 2014

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Presentations 【 Display / hide 】

Eggshell-based Packing Materials for HPLC

Yuki Hiruta

HPLC 2022,

2022.06
,
Poster presentation
Development of Furimazine Derivatives for Long-Term Bioluminescence Imaging

蛭田勇樹

日本顕微鏡学会　第78回学術講演会,

2022.05
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Oral presentation (invited, special)
炭酸カルシウムを母体とするHPLC用充填剤の開発

蛭田勇樹

日本化学会第101春季年会,

2022.03
,
Poster presentation
Development of caged luciferin enabling spatiotemporal trans-scale imaging

Yuki Hiruta

Pacifichem 2021,

2021.12

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2121.12
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Oral presentation (general)
Development of stimuli-responsive polymers for diagnostic and therapeutic applications

Yuki Hiruta

2021 MRS-T International Conference,

2021.11
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Oral presentation (invited, special)

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

がんバイオマーカー応答性高分子設計を戦略とした光セラノスティクス薬剤の開発

2021.04

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2024.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator
時空間トランススケールイメージングを可能にする超分子ケージドルシフェリンの開発

2021.04

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2023.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas, Principal investigator
Development of polymer caged luciferin enabling spatiotemporal trans-scale imaging

2019.04

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2021.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas, Principal investigator
Development of tumor self-accumulating functionalized theranostics nanoplatform

2019.04

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2021.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, 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

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2021.03

Coinvestigator(s)

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Awards 【 Display / hide 】

Best Poster Award HPLC 2022, San Diego

2022.06

Type of Award： Award from international society, conference, symposium, etc.
Outstanding Reviewer for journal of Materials Chemistry B

2021.03

Type of Award： Award from publisher, newspaper, foundation, etc.
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： Award from Japanese society, conference, symposium, etc.
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： Award from Japanese society, conference, symposium, etc.
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： Award from Japanese society, conference, symposium, etc.