Details of a Researcher

Hiruta, Yuki

写真a

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

Position: Associate Professor

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Career 【 Display / hide 】

2010.04

-

2011.03

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

-

2013.03

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

-

2017.03

Keio University, Faculty of Pharmacy, Assistant Professor
2017.04

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2023.03

Keio University, Faculty of Science and Technology, Senior Assistant Professor
2023.04

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Present

Keio University, Faculty of Science and Technology, Associate Professor

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Academic Background 【 Display / hide 】

2004.04

-

2008.03

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

University, Graduated
2008.04

-

2010.03

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

Graduate School, Completed, Master's course
2010.04

-

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

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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 】

Evaluation of separation performance for eggshell-based reversed-phase HPLC columns by controlling particle size and application in quantitative therapeutic drug monitoring

Yoshii T., Nakano K., Okuda T., Citterio D., Hiruta Y.

Analytical Methods （Analytical Methods) 15 （ 14 ） 1790 - 1796 2023.03

ISSN 17599660

　View Summary

Eggshell-based reversed-phase packing materials were applied to an analytical column for high-performance liquid chromatography. Commercially available eggshell powder was classified by a cyclone system to obtain three types of particles with different diameters (arithmetic mean ± standard deviation: 4.3 ± 3.8, 5.6 ± 3.3, and 9.5 ± 5.5 μm). Sedimentation separation removed tiny particles from each sample, resulting in particles with arithmetic means of 6.6 ± 5.5, 7.3 ± 4.5, and 10.2 ± 5.0 μm, respectively. The unclassified particles and three particle types treated with sedimentation separation were subsequently packed into analytical columns (150 mm × 4.6 mm I.D.), and their separation efficiencies were evaluated by comparing their height equivalent to a theoretical plate (HETP). The column without sedimentation separation exhibited the highest HETP, whereas the columns with sedimentation separation showed better separation efficiency and lower back pressure. The column with the best separation efficiency was applied for the separation of 10 alkylbenzenes and 5 steroids, and all peaks were observed with complete separation (peak resolution: RS > 1.5). Finally, the column was used for quantitative analysis of voriconazole, an azole antifungal agent, and imatinib, a first-generation molecularly targeted drug for cancer treatment, in spiked whole blood. Excellent accuracy (99.1-102.8%) and precision (0.6-1.9%) were observed for the spiked drugs and long-term stability (>3000 column volumes of mobile phase flow) indicated good applicability of the developed eggshell-based column as an analytical column for routine analyses of therapeutic drugs in blood.
- Access to Document (DOI)
Evaluation of cellophane as platform for colorimetric assays on microfluidic analytical devices

Shigemori Hiroki, Maejima Kento, Shibata Hiroyuki, Hiruta Yuki, Citterio Daniel

MICROCHIMICA ACTA （Microchimica Acta) 190 （ 2 ） 2023.02

ISSN 0026-3672

　View Summary

Due to their low cost, simplicity, and pump-free liquid transport properties, colorimetric assays on paper spots and microfluidic paper-based analytical devices (µPADs) are regarded as useful tools for point-of-care testing (POCT). However, for certain types of colorimetric assays, the “non-transparent” and “white” characters of paper can be a disadvantage. In this work, the possibilities of using cellophane as an alternative platform for colorimetric assays have been investigated. Cellophane is a low cost and easy-to-handle transparent film made of regenerated cellulose. Owing to its hydrophilic character, cellophane-based microfluidic channels fabricated through a print–cut–laminate approach enabled pump-free liquid transport into multiple detection areas, similar to µPADs. In addition, the water absorption characteristics of cellophane allowed the stable immobilization of water-soluble colorimetric indicators without any surface modification or additional reagents. The transparency of cellophane provides possibilities for simple background coloring of the substrates, increasing the dynamic signal range for hue-based colorimetric assays, as demonstrated for two model assays targeting H2O2 (46-fold increase) and creatinine (3.6-fold increase). Finally, a turbidity detection-based protein assay was realized on black background cellophane spots. The lowest limits of detection achieved with the cellophane-based devices were calculated as 7 µM for H2O2, 2.7 mg dL−1 for creatinine, and 3.5 mg dL−1 for protein (human serum albumin). Graphical Abstract: [Figure not available: see fulltext.]
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Fabrication process development and basic evaluation of eggshell-based column packing material for reversed-phase preparative separation

Yoshii Tomoka, Sakama Akihiro, Kanamori Kazuyoshi, Nakanishi Kazuki, Imai Hiroaki, Citterio Daniel, Hiruta Yuki

JOURNAL OF CHROMATOGRAPHY A （Journal of Chromatography A) 1688 2023.01

ISSN 0021-9673

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Purification of basic drugs in reversed-phase mode is often difficult, mainly due to adsorption of positively charged compounds to the silica gel-based stationary phase. Since this adsorption can be suppressed under alkaline condition, columns with alkali-resistance are required. In addition, compounds with acid-sensitive structures are sometimes degraded during separation on silica gel-based columns which exhibit acidity due to their surface structure. We prepared an alkali-resistant reversed-phase packing material, Eggshell-PMAcO based on eggshells modified with an amphiphilic copolymer, poly(maleic acid-alt-1-octadecene) (PMAcO). The height equivalent to a theoretical plate (HETP) of the Eggshell-PMAcO column was improved by surface treatment with ammonium acetate buffer (900 mM, pH = 3.7), which is an inexpensive reagent, and the retention behavior for hydrophobic compounds was compared to a typical ODS column based on silica gel, resulting in sufficient selectivity of the eggshell-based column for hydrophobic compounds, as indicated by the ratio of retention factors of pentylbenzene and butylbenzene (Eggshell-PMAcO column: 1.55, ODS column: 1.65). Column temperature-dependent retention behavior of naphthalene was investigated in the temperature range from 25 °C to 45 °C, followed by the calculation of thermodynamic parameters. There was little difference in the standard molar enthalpy (Eggshell-PMAcO: −19.6 kJ/mol, ODS: −21.7 kJ/mol). The absolute value of the standard free Gibbs energy for the Eggshell-PMAcO column was much smaller than that of the ODS column (Eggshell-PMAcO: −0.284 kJ/mol, ODS: −13.0 kJ/mol), indicating that the Eggshell-PMAcO column had a weaker retention strength for naphthalene than the ODS column mainly due to the large difference in the standard molar entropy (Eggshell-PMAcO: −64.9 J/mol K, ODS column: −29.2 J/mol K). The retention capacities for imipramine under neutral (water/methanol) and alkaline (0.1% triethylamine water/methanol) conditions were 0.2 mg and 5 mg, respectively, based on injection mass-dependent HETP, retention factor and symmetry factor. Finally, the prepared column was applied to the purification of a building block for nucleic acid drugs. This study demonstrated that reversed-phase columns, which can be fabricated from eggshells and an amphiphilic copolymer in an inexpensive and eco-friendly way, have the ability to purify basic compounds and acid-sensitive compounds.
- Access to Document (DOI)
Effect of the side chain composition of mixed-charge polymers on pH-selective cell–membrane interactions

Nakamura Y., Nasu M., Shindo Y., Oka K., Citterio D., Hiruta Y.

Polymer Journal （Polymer Journal) 2023

ISSN 00323896

　View Summary

Zwitterionic polymers are characterized by their antifouling ability due to their net-neutral charge and affinity for cancer cell surfaces. We developed six pH-responsive mixed-charge polymers and investigated the effect of their side chain hydrophobicity on their interaction with cancer cell membranes. The polymers were synthesized using [2-(methacryloyloxy)ethyl]trimethylammonium chloride, carboxylic acid monomers, and butyl methacrylate (BMA) as the neutral spacer moiety, and differences in hydrophobicity were created by altering the type of carboxylic acid monomer and ratio of the spacer. The surface charge of the polymers was designed to switch from net-neutral to positive in response to the weakly acidic tumor environment. This tuning occurred in a more cancer-like environment with the usage of a more hydrophobic anionic monomer and a higher ratio of BMA due to the weakening of electrostatic interactions. This trend was further confirmed by evaluation of the interaction between the polymers and heparin, an anionic polysaccharide that is used as a model for cancer cell surfaces. The affinity of the mixed-charge polymers for cells was then evaluated, and both the hydrophobicity and pH-responsive nature of these polymers led to pH-selective toxicity, which was assumed to be caused by the disruption of cell membrane integrity.
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Amphiphilic Copolymer-Modified Eggshell-Based Column Packing Materials for the Preparative Separation of Basic Drugs

Yoshii T., Mochida M., Kaizu K., Soda Y., Kanamori K., Nakanishi K., Sato T., Imai H., Citterio D., Hiruta Y.

ACS Applied Polymer Materials （ACS Applied Polymer Materials) 4 （ 10 ） 6949 - 6957 2022.10

ISSN 2637-6105

　View Summary

A way to utilize eggshells is desired because most of the eggshell waste is disposed of in landfills. Despite eggshells having attractive features such as a thermodynamically stable porous crystalline structure, their effective utilization as a functional material has yet to be demonstrated. Herein, we developed an alkali-stable column packing material for reversed-phase preparative high-performance liquid chromatography (HPLC) based on eggshells. Nanocrystals and biopolymers present on eggshell powder were removed by surface treatment with buffered ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite solutions, resulting in bare calcium carbonate with a uniform porous surface. The obtained particles were modified with poly(maleic acid-alt-1-octadecene) (PMAcO) having hydrophobic alkyl chains and anionic carboxylate groups. The prepared PMAcO-modified eggshell-based material was applied to an HPLC column, and its performance is evaluated. The column succeeded in the separation of alkylbenzenes, steroids, and diastereomers. It was also used for the separation of basic tricyclic antidepressants in an alkaline mobile phase, showing excellent retention capacity and alkali stability. This study demonstrates the potential of eggshell utilization, providing not only a practical stationary phase for HPLC but also a solution for recycling calcium carbonate-based biomineral waste.
- 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
,
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
,
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.