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Foundational Research

㈱TearExoのベースとなる
神戸大学の基礎研究

Introduction

(1)はじめに

標的分子の鋳型をポリマーで取る技術、分子インプリンティングは、天然の抗体と同様、標的分子を選択的に認識可能な、分子インプリントポリマー(MIP)を得る方法として知られ、MIPは人工抗体とも呼ばれる。安価・安定に大量生産できることから、高価で不安定な生体材料に替わる材料として注目されている。私達は、このMIPをさらに高機能化するための新しい戦略、インプリンティング後にさらに化学修飾を施すポストインプリンティング修飾(PIM)を提案している。これは、生体で行われているタンパク質が生合成されたのちに化学修飾されて高機能タンパク質を生み出す、翻訳「後」修飾(PTM)と同様に、分子の鋳型を取った後、さらに機能性分子でPIMを行うことで、結合特性の調整、結合情報の可視化、分子認識能のスイッチングなど、従来法では達成できなかった多機能化を達成する。認識対象は多岐にわたり、抗生物質や環境ホルモンからタンパク質、細胞外小胞エクソソーム、細胞にいたる様々な物質に適用可能である。

TearExo Method

(2)細胞外小胞エクソソームに対するPIMを用いたTearExo法の開発

TearExo法に用いられるセンシングチップの大きな特徴は、涙液中の細胞外小胞を見分けるために、「生体由来抗体と人工高分子受容体を空間的に統合したハイブリッド認識界面」を備えている点にある。まず、分子インプリンティングにより、細胞外小胞の形や表面の性質に合う人工のくぼみをポリマー材料の表面につくる。このくぼみは、細胞外小胞と同様のサイズに調製可能である。

さらに、PIMにより、このくぼみの中だけに、生体由来の抗体と蛍光分子を選択的に配置する。これにより、くぼみ自体が細胞外小胞を形や表面性質でとらえ、くぼみ内部に固定された抗体が特定の表面マーカーを確認し、同じ空間に置かれた蛍光分子が結合を信号として知らせる、という一連の働きを一つの認識空間で実現できる。

従来の抗体だけを使う方法に比べて、人工材料による安定性や設計自由度を活かせる一方、人工材料だけでは難しい高い分子識別性を抗体によって補える点が独創的である。つまりTearExo法のチップは、人工材料の丈夫さと抗体の正確な見分ける力を、標的が入る"くぼみ"の中に集約したハイブリッド型センサーであり、微量の涙液から細胞外小胞を高感度に検出するための技術である。

JACS Cover
Angew. Chem. Cover

Protein Imprinting

(3)タンパク質に対するPIMを用いた分子インプリンティング

がんを検知・診断するためのバイオマーカータンパク質を高感度・高選択的に認識・検出するための人工高分子材料を分子インプリンティングとPIMの技術を用いて開発した。

PSA(前立腺がんマーカー) Sci. Technol. Adv. Mater. 2019, 20 (1), 305-312.
AFP(肝がんマーカー) Angew. Chem. Int. Ed. 2016, 55, 13023-13027.
チトクロームc(ミトコンドリア中ヘムタンパク質) Chem. Commun. 2013, 49, 8450-8452.
タンパク質MIP
タンパク質構造

Oriented Imprinting

(4)配向固定化した鋳型分子を用いた分子インプリンティング

従来の分子インプリンティングは、重合中、鋳型分子が自由運動するため、取れる鋳型の均一性が低かった。鋳型分子を単に固定化して自由運動を低減するだけではなく、配向固定化することで、鋳型の均一性が格段に向上する。配向固定化とPIMを組み合わせることにより、従来のMIPに比べ、高い機能性をもつMIPが創製可能である。

これまでの分子インプリンティング
配向性分子インプリンティング
PSA(前立腺がんマーカー) Sci. Technol. Adv. Mater. 2019, 20 (1), 305-312.
AFP(肝がんマーカー) ChemNanoMat 2019, 5 (2), 224-229.
オボアルブミン(卵アレルゲン糖タンパク質) Langmuir 2019, 35 (5), 1320-1326.
血管内皮増殖因子(VEGF, がんマーカー) ACS Sensors 2018, 8, 3 (3), 580-586.
コルチゾール(ストレスマーカー) R. Soc. Open Sci. 2017, 4, 170300.
CRP(炎症マーカー) Chem. Commun. 2016, 52, 3883-3886.

Small Molecule Imprinting

(5)低分子(抗生物質・環境ホルモン)に対するPIMを用いた分子インプリンティング

環境ホルモンや抗生物質などの生物活性低分子化合物を高感度・高選択的に認識・検出するための人工高分子材料を分子インプリンティングとPIMの技術を用いて開発した。

ビスフェノールA(内分泌撹乱物質) J. Am. Chem. Soc. 2009, 131, 8833-8838.
低分子PIM

MIP Array

(6)MIP-アレイフォーマット

複数のMIPを用い、それぞれのMIPに対する結合特性を多変量解析することで、標的タンパク質をフィンガープリント化して区別することが可能であった。従来のプロテインチップに代わる保存安定性が高く安価なプロテイン解析法として期待される。

MIPアレイ(リボヌクレアーゼA-MIP・リゾチーム-MIP・ミオグロビン-MIP) Anal. Chem. 2015, 87, 11784-11791.
MIPアレイ(チトクロームc-MIP・リボヌクレアーゼA-MIP・ラクトアルブミン-MIP) Analyst 2007, 132, 101.
The Analyst Cover

Nanomedicine

(7)分子インプリントナノ材料をベースにしたナノメディシンのための薬物送達システムの開発

ナノ材料は、次世代医療のためのナノメディシンとして期待されている。特定のタンパク質を認識する分子インプリントナノ材料を用いて高機能性薬物送達システムを創製し、従来困難であった難治性疾患のためのナノメディシンの開発を開発する。本研究は、材料の設計合成から動物実験に至る広範囲な知識と技術が必要なことから、東京大学、神戸大学、大阪市立大学と協力して研究を遂行している。

ナノメディシン研究
Angew. Chem. Cover 2017

SPR Sensing

(8)表面プラズモン共鳴を利用したセンシング

プラズモニックチップ(波長オーダーの周期構造をもつ金属薄膜被覆センサチップ)を用いた増強蛍光によるバイオマーカー超高感度センシングデバイスの開発を関西学院大学と協力して行っている。また、局在表面プラズモン共鳴とMIPあるいは特異リガンドをもつポリマーナノ粒子を合成し、共鳴吸収波長のシフトを利用したバイオマーカーの検出を行った。

表面プラズモン共鳴

MIP Nanoparticle Sensing

(9)MIPナノ粒子によるセンシング

ストレスマーカーのコルチゾールを認識するMIPナノ粒子を設計・合成し、蛍光偏光解消法により高感度にコルチゾールのセンシングを行った。

MIPナノ粒子

Automated Analysis

(10)全自動バイオ分析システム

カスタムメイドで顕微鏡を装着した自動分注蛍光計測装置を開発し、抗体、DNA、MIPなどが固定化された微小反応板が挿入可能な特殊扁平ピペットチップを用いて、全自動バイオ分析システムを構築した。この業績により、株式会社TearExo CTOの高野が、2025年日本分析化学会女性アナリスト賞を授与された。

全自動バイオ分析システム

Publications

(11)研究論文リスト

原著論文

モレキュラーインプリンティング法によるバイオミメティック材料の創製(Biomimetic materials prepared by molecular imprinting techniques)

[1] Sunayama, H., Matsui, Y., Takeuchi, T. Functional Molecule-Integrated Nano-Interfaces for Detection of Extracellular Vesicles, Adv. Sensor Res. 2025, 4, 2400186. (DOI: 10.1002/adsr.202400186)

[2] Sunayama, H, Cheubong, C, Takano, E., Takeuchi, T., Facile biotic/abiotic sandwich detection system for the highly sensitive detection of human serum albumin and glycated albumin, Anal. Bioanal. Chem. 2024, 416, 7337-7345. (DOI: 10.1007/s00216-024-05403-9)

[3] Fukutomi, K., Fujimoto, E., Shimokawatoko, M., Takano, E., Sunayama, S., Takeuchi, T., Tawa, K. Single-Extracellular-Vesicle Detection with a Plasmonic Chip and Enhanced Fluorescence Microscopy, ACS Omega 2024, 9, 44396-44406. (DOI: 10.1021/acsomega.4c05678)

[4] Cheubong, C., Sunayama, H., Takano, E., Kitayama, Y., Minami, H., Takeuchi, T. A Rapid Abiotic/Biotic Hybrid Sandwich Detection System for Trace Pork Adulteration in Halal Meat Extract, Nanoscale 2023, 15, 15171-15178. (DOI: 10.1039/d3nr02863a)

[5] Mizutani, K., Kanda, M., Sunayama, H., Takeuchi, T., Tawa, K., New plasmonic sensor platform using a spatially controlled photochemical reaction and enhanced fluorescence, J. Photochem. Photobiol. A Chem. 2022, 433, 114177. (DOI: 10.1016/J.JPHOTOCHEM.2022.114177)

[6] Kitayama, Y., Yamada, T., Kiguchi, K., Yoshida, A., Hayashi, S., Akasaka, H., Igarashi, K., Nishimura, Y., Matsumoto, Y., Sasaki, R., Takano, E., Sunayama, H., Takeuchi, T. In vivo stealthified molecularly imprinted polymer nanogels incorporated with gold nanoparticles for radiation therapy, J. Mater. Chem. B 2022, 10, 6784-6791. (DOI: 10.1039/D2TB00481J)

[7] Oshita, A, Sunayama, H., Takeuchi, T. A molecularly imprinted nanocavity with transformable domains that fluorescently indicate the presence of antibiotics in meat extract samples, J. Mater. Chem. B 2022, 10, 6682-6687. (DOI: 10.1039/d2tb00145d)

[8] Hayakawa, N., Kitayama, Y., Igarashi, K., Matsumoto, Y., Takano, E., Sunayama, H., Takeuchi, T. Fc domain-imprinted stealth nanogels capable of orientational control of immunoglobulin G adsorbed in vivo, ACS Applied Mater. Interfaces 2022, 14, 16074-16081. (DOI: 10.1021/acsami.2c01953)

[9] Yoshida, A., Kitayama, Y., Hayakawa, N., Mizukawa, Y., Nishimura, Y., Takano, E., Sunayama, H., Takeuchi, T. Biocompatible polymer-modified gold nanocomposites of different shapes as radiation sensitizers, Biomater. Sci. 2022, 10, 2665-2672. (DOI: 10.1039/D2BM00174H)

[10] Cheubong, C., Takano, E., Kitayama, Y., Sunayama, H., Minamoto, K., Takeuchi, R., Furutani, S., Takeuchi, T., Molecularly imprinted polymer nanogel-based fluorescence sensing of pork contamination in halal meat extracts, Biosens. Bioelectron. 2021, 172, 112775. (DOI: 10.1016/j.bios.2020.112775)

[11] Tsutsumi, K., Sunayama, H., Kitayama, H., Takano, E., Nakamachi, Y., Sasaki, R., Takeuchi, T., Fluorescent signaling of molecularly imprinted nanogels prepared via postimprinting modifications for specific protein detection, Adv. NanoBiomed Res. 2021, 1, 2000079. (DOI: 10.1002/anbr.202000079)

[12] Sunayama, H., Takamiya, K., Takano, E. Horikawa, R., Kitayama, Y., Takeuchi, T., Simultaneous detection of two tumor marker proteins using dual-colored signaling molecularly imprinted polymers prepared via multi-step post-Imprinting modifications, Bull. Chem. Soc. Jpn. 2021, 94, 525-531. (DOI: 10.1246/bcsj.20200254)

[13] Sunayama, H., Takeuchi, T., Protein-imprinted polymer films prepared via cavity-selective multi-step post-imprinting modifications for highly selective protein recognition, Anal. Bioanal. Chem. 2021, 413, 6183-6189. (DOI: 10.1007/S00216-021-03386-5)

[14] Ikegami, T., Kataoka, R., Sunayama, H., Takeuchi, T., In silico characterization of binding properties on a molecularly imprinted polymer, BUNSEKIKAGAKU 2021, 70, 111-124. (DOI: 10.2116/BUNSEKIKAGAKU.70.111)

[15] Morishita, T., Yoshida, A., Hayakawa, N., Kiguchi, K., Cheubong, C., Sunayama, H., Kitayama, Y., Takeuchi, T., Molecularly imprinted nanogels possessing dansylamide interaction sites for controlling protein corona in situ by cloaking intrinsic human serum albumin, Langmuir 2020, 36, 10674-10682. (DOI: 10.1021/acs.langmuir.0c00927)

[16] Kitayama, Y., Takeuchi, T., Photodegradable polymer capsules fabricated via interfacial photocross-linking of spherical polymer particles, ACS Appl. Polym. Mater. 2020, 2, 3813-3820. (DOI: 10.1021/acsapm.0c00472)

[17] Saeki, T., Takano, E., Sunayama, H., Kamon, Y., Horikawa, R., Kitayama, Y., Takeuchi, T., Signalling molecular recognition nanocavities with multiple functional groups prepared by molecular imprinting and sequential post-imprinting modifications for prostate cancer biomarker glycoprotein detection, J. Mater. Chem. B 2020, 8, 7987-7993. (DOI: 10.1039/D0TB00685H)

[18] Inubushi, S., Kawaguchi, H., Mizumoto, S., Kunihisa, T., Baba, M., Kitayama, Y., Takeuchi, T., Hoffman, R. M., Sasaki, R., Oncogenic miRNAs identified in tear exosomes from metastatic breast cancer patients, Anticancer Res. 2020, 40, 3091-3096. (DOI: 10.21873/anticanres.14290)

[19] Takeuchi, T., Mori, K., Sunayama, H., Takano, E., Kitayama, Y., Shimizu, T., Hirose, Y., Inubushi, S., Sasaki, R., Tanino, H. Antibody-conjugated signaling nanocavities fabricated by dynamic molding for detecting cancers using small extracellular vesicle markers from tears, J. Am. Chem. Soc. 2020, 142, 6617-6624. (DOI: 10.1021/jacs.9b13874)

[20] Cheubong, C., Yoshida, A., Mizukawa, Y., Hayakawa, N., Takai, M., Morishita, T., Kitayama, Y., Sunayama, H., Takeuchi, T. Molecularly imprinted nanogels capable of porcine serum albumin detection in raw meat extract for halal food control, Anal. Chem. 2020, 92, 6401-6407. (DOI: 10.1021/acs.analchem.9b05499)

[21] Hayakawa, N., Yamada, T., Kitayama, Y., Takeuchi, T., Cellular interaction regulation by protein corona control of molecularly imprinted polymer nanogels using intrinsic proteins, ACS Appl. Polym. Mater. 2020, 2, 1465-1473. (DOI: 10.1021/acsapm.9b01149)

[22] Uchiyamada, K., Okubo, K., Asakawa, K., Kamon, Y., Kitayama, Y., Takeuchi, T., Suzuki, H. Perforated bimodal interferometric biosensor for affinity sensing, Adv. Mater. Technol. 2019, 4, 1800533. (DOI: 10.1002/admt.201800533)

[23] Yoshida, A.; Kitayama, Y.; Kiguchi, K.; Yamada, T.; Akasaka, H.; Sasaki, R.; Takeuchi, T. Gold nanoparticle-incorporated molecularly imprinted microgels as radiation sensitizers in pancreatic cancer, ACS Appl. Bio Mater. 2019, 2, 1177-1183. (DOI: 10.1021/acsabm.8b00766)

[24] Matsumoto, H., Sunayama, H., Kitayama, Y., Takano, E., Takeuchi, T. Site-specific post-imprinting modification of molecularly imprinted polymer nanocavities with a modifiable functional monomer for prostate cancer biomarker recognition, Sci. Technol. Adv. Mater. 2019, 20, 305-312. (DOI: 10.1080/14686996.2019.1583495)

[25] Mori, K., Hirase, M., Morishige, T., Takano, E., Sunayama, H., Kitayama, Y., Inubushi, S., Sasaki, R., Yashiro, M., Takeuchi, T. A pretreatment-free, polymer-based platform prepared by molecular imprinting and post-imprinting modifications for sensing intact exosomes, Angew. Chem. Int. Ed. 2019, 58 (6), 1612-1615. (DOI: 10.1002/anie.201811142)

[26] Morishige, T., Takano, E., Sunayama, H., Kitayama, Y., Takeuchi, T. Post-imprinting-modified molecularly imprinted nanocavities with two synergetic, orthogonal, glycoprotein-binding sites to transduce binding events into fluorescence changes, ChemNanoMat 2019, 5 (2), 224-229.

[27] Saeki, T., Sunayama, H., Kitayama Y., Takeuchi, T. Orientationally fabricated zwitterionic molecularly imprinted nanocavities for highly sensitive glycoprotein recognition, Langmuir 2019, 35, 5, 1320-1326.

[28] Kitayama, Y., Takeuchi, T. Morphology control of shell-crosslinked polymer particles fabricated by photo-induced shell-selective crosslinking approach via dispersed state control, J. Colloid Interface Sci. 2018, 530, 88-97.

[29] Ichikawa, S., Shimokawa, N., Takagi, M., Kitayama, Y., Takeuchi, T., Size-dependent uptake of electrically neutral amphipathic polymeric nanoparticles by cell-sized liposomes and an insight into their internalization mechanism in living cells, Chem. Commun. 2018, 54, 4557-4560.

[30] Kamon, Y., Takeuchi, T. Molecularly imprinted nanocavities capable of ligand-binding domain and size/shape recognition for selective discrimination of vascular endothelial growth factor isoforms, ACS Sens. 2018, 3 (3), 580-586.

[31] Ooya, T., Ogawa, T., Takeuchi, T. Temperature-induced recovery of a bioactive enzyme using polyglycerol dendrimers: correlation between bound water and protein interaction, J. Biomater. Sci., Polym. Ed. 2018, 29 (6), 701-715.

[32] Uchiyamada, K., Okubo, K., Asakawa, Y., Kamon, Y., Kitayama, Y., Takeuchi, T., Suzuki, H. Directional coupler biosensor with molecularly imprinted polymer, Sens. Mater. 2018, 30 (5), 1009-1017.

[33] Kitayama, Y., Yoshikawa, K., Takeuchi, T. Post-Crosslinked Molecular Imprinting with Functional Polymers as a Universal Building Block for Artificial Polymeric Receptors, Macromolecules 2017, 50 (19), 7526-7534.

[34] Suda, N., Sunayama, H., Kitayama, Y., Kamon, Y., Takeuchi, T. Oriented, Molecularly Imprinted Cavities with Dual Binding Sites for Highly Sensitive and Selective Recognition of Cortisol, R. Soc. Open Sci. 2017, 4, 170300. (DOI: 10.1098/rsos.170300)

[35] Kitayama, Y., Takeuchi, T. Fabrication of Redox-responsive Degradable Capsule Particles via Shell-Selective Photo-induced Crosslinking Approach from Spherical Polymer Particles, Chem. Eur. J. 2017, 23, 12870-12875.

[36] Takeuchi, T., Kitayama, Y, Sasao, R., Yamada, T., Toh, K., Matsumoto, Y., Kataoka, K. Molecularly Imprinted Nanogels Acquire Stealth in situ by Cloaking Themselves with Native Dysopsonic Proteins, Angew. Chem. Int. Ed. 2017, 56, 7088-7092. [Hot Paper]

[37] Sunayama, H., Kitayama, Y., Takeuchi, T. Regulation of Protein Binding Activities of Molecularly Imprinted Polymers via Post-imprinting Modifications to Exchange Functional Groups within the Imprinted Cavity, J. Mol. Recogn. 2017, 31, e2633.

[38] Ohmori, K., Ooya, T., Takeuchi, T. Crosslinked Network with Rotatable Binding Sites Based on Mono-carboxylated a-Cyclodextrin [2]Rotaxane Capable of Angiotensin III Recognition, Chem. Eur. J. 2017, 23 (19), 4708-4712.

[39] Nakai, S.; Sunayama, H.; Kitayama, Y.; Nishijima, M.; Wada, T.; Inoue, Y. Takeuchi, T. A Regioselective Molecularly Imprinted Reaction Field for the [4+4] Photocyclodimerization of 2-Anthracenecarboxylic Acid, Langmuir 2017, 33, (9), 2103-2108.

[40] Sunayama, H., Ohta, T., Kuwahara, A., Takeuchi, T. Fluorescent Signaling Molecularly Imprinted Polymers for Antibiotics Prepared via Site-Directed Post-Imprinting Introduction of Plural Fluorescent Reporters within the Recognition Cavity, J. Mater. Chem. B 2016, 4, 7138-7145.

[41] Sunayama, H., Ohta, T., Kuwahara, A., Takeuchi, T. Fluorescent Signaling Molecularly Imprinted Polymers for Antibiotics Prepared via Site-Directed Post-Imprinting Introduction of Plural Fluorescent Reporters within the Recognition Cavity, J. Mater. Chem. B 2016, 4, 7138-7145.

[42] Horikawa, R., Sunayama, H., Kitayama, Y. Takano, E., Takeuchi, T. Programmable signaling molecular recognition nano-cavity prepared by molecular imprinting and post-imprinting modifications, Angew. Chem. Int. Ed. 2016, 55, 13023-13027.

[43] Kitayama, Y., Yoshikawa, K., Takeuchi, T. An efficient pathway for preparing hollow particles: site-specific crosslinking of spherical polymer particles with photo-responsive groups that play a dual role in shell crosslinking and core shielding, Langmuir 2016, 32, 9245-9253.

[44] Kamon, Y., Inoue, Mihara, E., Kitayama, Y., Ooya, T., Takeuchi, T. Hydrophilic crosslinked-polymeric surface capable of effective suppression of protein adsorption, Appl. Surf. Sci. 2016, 378, 467-472.

[45] Murase, N., Mukawa, T., Sunayama, H., Takeuchi, T. Molecularly imprinted polymers bearing spiropyran-based photoresponsive binding sites capable of photo-triggered switching for molecular recognition activity, J. Polym. Sci. B: Polym. Phys. 2016, 54, (16) 1637-1644.

[46] Murase, N., Taniguchi, S., Takano, E., Kitayama, Y., Takeuchi, T. Molecularly imprinted nanocavity-based fluorescence polarization assay platform for cortisol sensing, J. Mater. Chem. B 2016, 4, 1770-1777.

[47] Matsuura, R,, Tawa, K., Kitayama, Y., Takeuchi, T. A plasmonic chip-based bio/chemical hybrid sensing system for the highly sensitive detection of C-reactive protein, Chem. Commun. 2016, 52, 3883-3886.

[48] Yoshizawa, S., Kuwata, T., Takano, E., Kitayama, Y., Takeuchi, T. Transcription-type protein imprinted polymers for SPR sensing prepared using target-immobilized stamps based on submicrometer-sized particles via biotin-avidin linkage, Molecular Imprinting 2016, 3, 26-34.

[49] Moriishi, M., Kitayama, Y., Ooya, T., Takeuchi, T. Amphiphilic polymerizable porphyrins conjugated to a polyglycerol dendron moiety as functional surfactants for multifunctional polymer particles, Langmuir 2015, 31, 12903-12910.

[50] Kuwata, T., Uchida, A., Takano, E., Kitayama, Y., Takeuchi, T. Molecularly imprinted polymer arrays as synthetic protein chips prepared by transcription-type molecular imprinting by use of protein-immobilized dots as stamps, Anal. Chem. 2015, 87, 11784-11791.

[51] Takimoto, K., Takano, E., Kitayama, Y., Takeuchi, T. Synthesis of monodispersed submillimeter-sized molecularly imprinted particles selective for human serum albumin using inverse suspension polymerization in water-in-oil emulsion prepared using microfluidics, Langmuir 2015, 31, 4981-4987.

[52] Murase, N., Taniguchi, S., Takano, E., Kitayama, Y., Takeuchi, T. Fluorescence reporting of binding interaction of target molecules with core-shell type cortisol imprinted polymer particles using environmentally responsible fluorescent-labeled cortisol, Macromol. Chem. Phys. 2015, 216, 1396-1404.

[53] Kamon, Y., Kitayama, Y., Itakura, A. N., Fukazawa, K., Ishihara, K., Takeuchi, T. Synthesis of grafted phosphorylcholine polymer layers as specific recognition ligands for C-Reactive protein focused on grafting density and thickness to achieve highly sensitive detection, Phys. Chem. Chem. Phys. 2015, 17, 9951-9958.

[54] Taguchi, H., Sunayama, H., Takano, E., Kitayama, Y., Takeuchi, T. Preparation of Molecularly imprinted polymers for the recognition of proteins via the generation of peptide-fragment binding sites by semi-covalent imprinting and enzymatic digestion, Analyst 2015, 140, 1448-1452.

[55] Sunayama, H., Takeuchi, T. Molecularly imprinted protein recognition cavities bearing exchangeable binding sites for postimprinting site-directed introduction of reporter molecules for readout of binding events, ACS Appl. Mater. Interfaces 2014, 6, 20003-20009.

[56] Kitamura, A., Kitayama, Y., Ooya, T., Takeuchi, T. Molecularly Imprinted Recognition Polymers for Catechin Recognition Prepared Using Dummy-Template Molecules, Chromatography 2014, 35, 139-145.

[57] Kitamura, A., Kitayama, Y., Ooya, T., Takeuchi, T. Molecularly imprinted polymers for catechin recognition prepared using dummy-template molecules, Chromatography 2014, 35, 139-145.

[58] Takeuchi, T., Mori, T., Kuwahara, A., Ohta, T., Oshita, A., Sunayama, H., Kitayama Y., Ooya, T. Conjugated protein mimics with molecularly imprinted reconstructible and transformable regions assembled using space-filling prosthetic groups, Angew. Chem. Int. Ed. 2014, 53, 12765-12770.

[59] Sasaki, S., Kitayama, Y., Ooya, T., Takeuchi, T. Molecularly imprinted protein recognition thin films constructed by controlled/living radical polymerization, J. Biosci. Bioeng. 2015, 119, 200-205.

[60] Kamon, Y., Matsuura, R., Kitayama, Y., Ooya, T., Takeuchi, T.. Precisely controlled molecular imprinting of glutathione-s-transferase by orientated template immobilization using specific interaction with an anchored ligand on a gold substrate, Polym. Chem. 2014, 5, 4764-4771.

[61] Kitayama, Y., Takeuchi, T.. Localized surface plasmon resonance nanosensing of C-reactive protein with poly(2-methacryloyloxyethyl phosphorylcholine)-grafted-gold nanoparticles prepared by surface-initiated atom transfer radical polymerization, Anal. Chem. 2014, 86, 5587-5594.

[62] Sunayama, H., Ooya, T., Takeuchi, T. Fluorescent protein-imprinted polymers capable of signal transduction of specific binding events prepared by a site-directed two-step postimprinting modification, Chem. Commun. 2014, 50, 1347-1349.

[63] Uchida, A., Kitayama, Y., Takano, E., Ooya, T., Takeuchi, T. Supraparticles comprised of molecularly imprinted nanoparticles and modified gold nanoparticles as a nanosensor platform, Rsc Advances 2013, 3, 25306-25311.

[64] Inoue, N., Ooya, T., Takeuchi, T. Hydrophilic molecularly imprinted polymers for bisphenol A prepared in aqueous solution, Microchim. Acta 2013, 180, 15, 1387-1392.

[65] Suga, Y., Sunayama , H., Ooya, T., Takeuchi, T. Molecularly imprinted polymers prepared using protein-conjugated cleavable monomers followed by site-specific post-imprinting introduction of fluorescent reporter molecules, Chem. Commun. 2013, 49, 8450-8452.

[66] Inoue, Y., Kuwahara, A., Ohmori, K., Sunayama, H., Ooya, T., Takeuchi, T. Fluorescent Molecularly Imprinted Polymer Thin Films for Specific Protein Detection Prepared with Dansyl Ethylenediamine-Conjugated O-Acryloyl L-Hydroxyproline Biosens. Bioelectron. 2013, 48, 113-119.

[67] Taguchi, Y., Takano, E., Takeuchi, T. SPR sensing of bisphenol A using molecularly imprinted nanoparticles immobilized on slab optical waveguide with consecutive parallel Au and Ag deposition bands coexistent with Bisphenol A-immobilized Au nanoparticles, Langmuir 2012, 28, 7083-7088.

[68] Takano, E., Tanaka, F., Ooya, T., Takeuchi, T. Molecularly Imprinted Microspheres for Bisphenol A Prepared Using a Microfluidic Device, Anal. Sci. 2012, 28, 457-462.

[69] Takano, E., Taguchi, Y., Ooya, T., Takeuchi, T. Dummy template-imprinted polymers for Bisphenol A prepared using a Schiff base-type template molecule with post-imprinting oxidation, Anal. Lett. 2012, 45, 1204-1213.

[70] Inoue, J., Ooya, T., Takeuchi, T. Protein imprinted TiO2-coated quantum dots for fluorescent protein sensing prepared by liquid phase deposition, Soft Matter 2011, 7, 9681-9684.

[71] Sasaki, S., Ooya, T., Takeuchi, T. Highly Selective Bisphenol A-Imprinted Polymers Prepared by Atom Transfer Radical Polymerization, Polym. Chem. 2010, 1, 1684-1688.

[72] Sunayama, H., Ooya, T., Takeuchi, T., Fluorescent Protein Recognition Polymer Thin Films Capable of Selective Signal Transduction of Target Binding Events Prepared by Molecular Imprinting with a Post-Imprinting Treatment, Biosens. Bioelectron. 2010, 26, 458.462.

[73] Takeda, K., Kuwahara, A., Ohmori K., Takeuchi, T. Molecularly Imprinted Tunable Binding Sites Based on Conjugated Prosthetic Groups and Ion-Paired Cofactors, J. Am. Chem. Soc. 2009, 131, 8833-8838.

[74] Shinmori, H., Furukawa, H., Fujimoto, K., Shimizu, H., Inouye, M., Takeuchi, T. Characteristic Fluorescence Behavior of Dialkynylpyrene Derivatives in Hydrophobic Cavity of Protein, Chem. Lett. 2009, 38, 84-85.

[75] Murakami, S., Yamamoto, K., Shinmori H., Takeuchi, T. A Molecularly Imprinted Polymer for the Reconstruction of a Molecular Recognition Region, Chem. Lett. 2008, 37, 1028-1029.

[76] Tatemichi, M., Sakamoto, M., Mizuhata, M., Deki, S., Takeuchi, T., Protein-templated Organic/inorganic Hybrid Materials Prepared by Liquid-phase Deposition, J. Am. Chem. Soc. 2007, 129, 10906-10910.

[77] Matsunaga, T., Hishiya, T., Takeuchi, T., Optimization of Functional Monomer Content in Protein-Imprinted Polymers, Anal. Lett. 2007, 40, 2633-2640.

[78] Takeuchi, T., Akeda, K., Murakami, S., Shinmori, H., Inoue, S., Lee, W.-S., Hishiya, T., Photoresponsive Porphyrin-imprinted Polymers Prepared Using a Novel Functional Monomer Having Diaminopyridine and Azobenzene Moieties, Org. Biomol. Chem. 2007, 5, 2368-.2374.

[79] Kutsumizu, R., Shinmori, H., Takeuchi, T., L-Lysine-linked Anthracenophane Derived from Thermodynamically Controlled Intermediates, Tetrahedron Lett. 2007, 48, 3225-3228.

[80] Matsunaga, T., Hishiya, T., Takeuchi, T., Surface Plasmon Resonance Sensor Based on Molecularly Imprinted Thin Films, Anal. Chim. Acta 2007, 591, 63-67.

[81] Takeuchi, T., Goto, D., Shinmori, H., Protein Profiling by Protein Imprinted Polymer Array, Analyst 2007, 132, 101-103.

[82] Yane, T., Shinmori, H., Takeuchi, T., Atrazine Transforming Polymer Prepared by Molecular Imprinting with Post-imprinting Process, Org. Biomol. Chem., 2006, 4, 4469-4473.

[83] Matsunaga, T., Takeuchi, T. Crystallized Protein-imprinted Polymer Chips, Chem. Lett. 2006, 35, 1030-1031.

[84] Kubo, A., Shinmori, H., Takeuchi, T. Atrazine-imprinted Microspheres Prepared Using a Microfluidic Device, Chem. Lett, 2006, 588-589.

[85] Takeuchi, T., Murase, N., Maki, H., Mukawa, T., Shinmori, H. Dopamine Selective Molecularly Imprinted Polymers via Post-Imprinting Modification, Org. Biomol. Chem. 2006, 4, 565-568.

[86] Takeuchi, T., Minato, Y., Takase, M., Shinmori, H. Molecularly Imprinted Polymers with Halogen Bonding-based Molecular Recognition Sites, Tetrahedron Lett. 2005, 46, 9025-9027.

[87] Lee, Woo-Sang, Takeuchi, T. Bisphenol A Analog-Imprinted Polymers Prepared by an Immobilized Template on a Modified Silica Microsphere Matrix, Anal. Sci. 2005, 21, 1125-1128.

[88] Takeuchi, T., Mukawa, T., Shinmori, H. Signaling Molecularly Imprinted Polymers: Molecular Recognition-based Sensing Materials, Chem. Records 2005, 5, 263-275.

[89] Navarro Villoslada, F., Takeuchi, T. Multivariate Analysis and Experimental Design In the Screening of Combinatorial Libraries of Molecular Imprinted Polymers, Bull. Chem. Soc. Jpn. 2005, 78, 1354-1361.

[90] Kubo, H., Yoshioka, N., Takeuchi, T. Fluorescent Imprinted Polymers Prepared with 2-Acrylamidoquinoline as a Signaling Monomer, Org. Lett. 2005, 7, 359 - 362.

[91] Takase, M., Nakajima, A., Takeuchi, T. Synthesis of an Extended Hexagonal Molecule as a Highly Symmetrical Ligand, Tetrahedron Lett. 2005, 46, 1739-1742.

[92] Takeuchi, T, Seko, A., Mukawa, T. Molecularly Imprinted Polymers with Signaling Function Based on the UV-Vis Spectral Change by Diastereoselective Binding Events, Bull. Chem. Soc. Jpn. 2005, 78, 356-360.

[93] Takeuchi, T., Ugata, S., Masuda, S., Matsui, J., Yane, T., Takase, M. Atrazine Tranformation Using Synthetic Enzymes Prepared by Molecular Imprinting, Org. Biomol. Chem. 2004, 2, 2563-2566.

[94] Ikegami T., Lee, W.-S., Nariai, H., Takeuchi, T. Covalent Molecular Imprinting of Bisphenol A Using Its Diesters Followed by the Reductive Cleavage with LiAlH4, J. Chromatogr. B 2004, 804, 197-201.

[95] Ikegami T., Lee, W.-S., Nariai, H., Takeuchi, T. Synthetic Polymers Adsorbing Bisphenol A and Its Analogues Prepared by Covalent Molecular Imprinting Using Bisphenol A Dimethacrylate as a Template Molecule, Anal. Bioanal. Chem. , 2004, 378, 1898-1902.

[96] Ikegami, T., Mukawa, T., Nariai, H., Takeuchi, T. Bisphenol A-recognition Polymers Prepared by Covalent Molecular Imprinting, Anal. Chim. Acta 2004, 504, 131-135.

[97] Kubo, H., Player, T. N., Shinoda, S Tsukube, H., Nariai, H., Takeuchi, T. Chiral Recognition of Octadentate Na+ Complex with Tetra-Armed Cyclen by Molecularly Imprinted Polymers, Anal. Chim. Acta 2004, 504, 137-140.

[98] Kubo, H., Nariai, H., Takeuchi, T "Multiple Hydrogen Bonding-based Fluorescent Imprinted Polymers for Cyclobarbital Prepared with 2,6-Bis(acrylamido)pyridine", Chem. Commun.. 2003, 2792-2793.

[99] Shoji, R., Takeuchi, T., Kubo, I. Atrazine Sensor Based on Molecularly Imprinted Polymer Modified Gold Electrode, Anal. Chem. 2003, 75, 4882-4886.

[100] Mukawa, T., Goto, T., Nariai, H., Aoki, Y., Imamura, A., Takeuchi, T. Novel Strategy for Molecular Imprinting of Phenolic Compounds Utilizing Disulfide Templates, J. Pharm. Biomed. Anal. 2002, 30, 1943-1947.

[101] Mukawa, T., Goto, T., Takeuchi, T. Post-Oxidative Conversion of Thiol Residue to Sulfonic Acid in the Binding Sites of Molecularly Imprinted Polymers: Disulfide Based Covalent Molecular Imprinting for Basic Compounds, Analyst 2002, 127, 1407-1409.

[102] Kugimiya, A., Takeuchi, T. Molecular Recognition in Indoleacetic Acid-Imprinted Polymers: Effect of 2-Hydroxyrthyl Methacrylate Contents, Anal. Bioanal. Chem. 2002, 372, 305-307.

[103] Kugimiya, A., Kuwada, Y., Takeuchi, T. Preparation of Sterol-Imprinted Polymers with the Use of 2-(Methacryloyloxy)ethyl Phosphate, J. Chromatogr. A 2001, 938, 131-135.

[104] Takeuchi, T., Mukawa, T., Matsui, J., Higashi, M., Shimizu, K. D. Molecularly Imprinted Polymers with Metalloporphyrin-Based Molecular Recognition Sites Coassembled with Methacrylic acid, Anal. Chem. 2001, 73, 3869-3874.

[105] Takeuchi, T., Fukuma, D., Matsui, J., Mukawa, T. Combinatorial Molecular Imprinting for Formation of Atrazine Decomposing Polymers, Chem. Lett. 2001, 530-531.

[106] Kugimiya, A., Takeuchi, T. Surface Plasmon Resonance Sensor Using Molecularly Imprinted Polymer for Detection of Sialic Acid, Biosens. Bioelectron. 2001, 16, 1059-1062.

[107] Kugimiya, A., Mukawa, T., Takeuchi, T. Synthesis of 5-Fluorouracil-Imprinted Polymers with Multiple Hydrogen Bonding Interaction, Analyst 2001, 126, 772-774.

[108] Takeuchi, T., Seko A., Matsui, J., Mukawa, T. Molecularly Imprinted Polymer Library on a Microtiter Plate: High-throughput Synthesis and Assessment of Cinchona Alkaloid-imprinted Polymers, Instrument. Sci. Technol. 2001, 29, 1-9.

[109] Matsui, J., Higashi, M., Takeuchi, T. Molecularly Imprinted Polymer as 9-Ethyladenine Receptor Having a Porphyrin-based Recognition Center, J. Am. Chem. Soc. 2000, 122, 5218-5219.

[110] Matsui, J., Kubo, H., Takeuchi, T. Molecularly Imprinted Fluorescent-shift Receptors Prepared with 2-(Trifluoromethyl)acrylic Acid, Anal. Chem. 2000, 72, 3286-3290.

[111] Takeuchi, T., Dobashi, A., Kimura, K. Molecular Imprinting of Biotin Derivatives and Its Application to Competitive Binding Assay Using Non-isotopic Labeled Ligands, Anal. Chem. 2000, 72, 2418-2422.

[112] Matsui, J., Fujiwara, K., Ugata, S., Takeuchi, T. Solid-Phase Extraction with a Dibutylmelamine-imprinted Polymer as Triazine Herbicide-selective Sorbent, J. Chromatogr. A, 2000, 889, 25-31.

[113] Kugimiya, A., Yoneyama, H., Takeuchi, T. Sialic Acid Imprinted Polymer-Coated Quartz Crystal Microbalance, Electroanalysis 2000, 12, 1322-1326.

[114] Matsui, J., Fujiwara, K., Takeuchi, T. Atrazine-Selective Polymers Prepared by Molecular Imprinting of Trialkylmelamines as Dummy Template Species of Atrazine, Anal. Chem. 2000, 72, 1810-1813.

[115] Takeuchi, T., Matsui, J. Miniaturized Molecularly Imprinted Continuous Polymer Rods, J. High Resolution Chromatogr. 2000, 23, 44-46.

[116] Takeuchi, T., Fukuma, D., Matsui, J. Combinatorial Molecular Imprinting: An Approach to Synthetic Polymer Receptors, Anal. Chem. 1999, 71, 285-290.

[117] Kugimiya, A., Takeuchi, T. Molecularly Imprinted Polymer-Coated Quartz Crystal Microbalance for Detection of Biological Hormone, Electroanalysis 1999, 11, 1158-1160.

[118] Kugimiya, A., Takeuchi, T. Effects of 2-Hydroxyethyl Methacrylate on Polymer Network and Interaction in Hydrophilic Molecularly Imprinted Polymers, Anal. Sci. 1999, 15, 29-33.

[119] Kugimiya, A., Takeuchi, T. Application of Indoleacetic acid-Imprinted Polymer to Solid Phase Extraction, Anal. Chim. Acta 1999, 395, 251-255.

[120] Matsui, J., Tachibana, Y., Takeuchi, T. Molecularly Imprinted Receptor having Metalloporphyrin-based Signaling Binding Site, Anal. Commun. 1998, 35, 225-227.

[121] Matsui, J., Kubo, H., Takeuchi, T. Design and Preparation of Molecularly Imprinted Atrazine-Receptor Polymers: Investigation of Functional Monomers and Solvents. Anal. Sci. 1998, 14, 699-702.

[122] Matsui, J., Nicholls, I. A., Takeuchi, T. Molecular Recognition in Cinchona Alkaloid Molecular Imprinted Polymer Rods. Anal. Chim. Acta 1998, 365, 89-93.

[123] Kugimiya, A., Matsui, J., Abe, H., Aburatani, M., Takeuchi, T. Synthesis of Castasterone Selective Polymers Prepared by Molecular Imprinting. Anal. Chim. Acta 1998, 365, 75-79.

[124] Takeuchi, T., Matsui, J. Recognition and Sensing of a Nucleobase by a Molecularly Imprinted Artificial Receptor, Nucleic Acids Symposium Series 1998, 39, 213-214.

[125] Yano, K.,Tanabe, K., Takeuchi, T., Matsui, J., Ikebukuro, K., Karube, I. Molecularly Imprinted Polymers which Mimic Hydrogen Bonds between Nucleotide Bases, Anal. Chim. Acta 1998, 363, 111-117.

[126] Yano, K, Nakagiri, T., Takeuchi, T., Matsui, J., Ikebukuro, K., Karube, I. Stereoselective Recognition of Dipeptide Derivatives in Molecularly Imprinted Polymers Which Incorporate an L-Valine Derivative as a Novel Functional Monomer, Anal. Chim. Acta 1997, 357, 91-98.

[127] Matsui, J., Takeuchi, T. A Molecularly Imprinted Polymer Rod as Nicotine Selective Affinity Media Prepared with 2-(Trifluoromethyl)acrylic Acid, Anal. Commun. 1997, 34, 199-200.

[128] Matsui, J., Doblhoff-Dier, O., Takeuchi, T. 2-(Trifluoromethyl)acrylic Acid: A Novel Functional Monomer in Non-covalent Molecular Imprinting, Anal. Chim. Acta. 1997, 343, 1-4.

[129] Kugimiya, A., Matsui, J., Takeuchi, T. Sialic acid-imprinted polymers using noncovalent interactions, Materials Sci. Eng. 1997, C4, 263-266.

[130] Matsui, J., Okada, M., Tsuruoka, M., Takeuchi, T. Solid-Phase Extraction of a Triazine Herbicide Using a Molecularly Imprinted Synthetic Receptor, Anal. Commun. 1997, 34, 85-87.

[131] Matsui, J., Nicholls, I. A., Takeuchi, T. Highly Stereoselective Molecular Imprinted Polymer Synthetic Receptors for Cinchona Alkaloids, Tetrahedron: Asymm. 1996, 7, 1357-1361.

[132] Matsui, J., Nicholls, I. A., Takeuchi, T., Mosbach, K., Karube, I. Metal Ion Mediated Recognition in Molecularly Imprinted Polymers, Anal. Chim. Acta 1996, 335, 71-77.

[133] Matsui, J., Kaneko, A., Miyoshi, Y., Yokoyama, K., Tamiya, E., Takeuchi, T. A Molecularly Imprinted Nicotine-selective Polymer, Anal. Lett. 1996, 29, 2071-2078.

[134] Kugimiya, A., Takeuchi, T., Matsui, J., Yano, K., Karube, I. Recognition in Novel Molecularly imprinted Polymer Sialic Acid Receptors in Aqueou Media, Anal. Lett. 1996, 29, 1099-1107.

[135] Piletsky, S. A., Piletskaya, E. V., Elgersma, A. V., Yano, K., Takeuchi, T., Karube, I., Panasyuk, T. I., El'skaya, A. V. A Biomimetic Receptor System for Sialic Acid Based on Molecular Imprinting, Anal. Lett. 1996, 29, 157-170.

[136] Kato, T., Takeuchi, T., Karube, I. Bis-imidazolyl Cleft-shaped Mimic of the Active Site of Ribonuclease A, J. Chem. Soc., Chem. Commun. 1996, 953-954.

[137] Matsui, J., Miyoshi, Y., Doblhoff-Dier, O., Takeuchi, T. A Molecularly Imprinted Synthetic Polymer Receptor Selective for Atrazine, Anal. Chem. 1995, 67, 4404-4408.

[138] Matsui, J., Miyoshi, Y., Matsui, R., Takeuchi, T. Rod-type Affinity Media for Liquid Chromatography Prepared by In-situ-molecular imprinting, Anal. Sci. 1995, 11, 1017-1019.

[139] Tanabe, K., Takeuchi, T., Matsui, J., Ikebukuro, K., Yano, K., Karube, I. Recognition of Barbiturates in Molecularly Imprinted Copolymers using Multiple Hydrogen Bonding, J. Chem. Soc. Chem. Commun. 1995, 2303-2304.

[140] Matsui, J., Miyoshi, Y., Takeuchi, T. Fluoro-functionalized Molecularly Imprinted Polymers Selective for Herbicides, Chem. Lett. 1995, 1007-1008.

[141] Matsui, J., Doblhoff-Dier, O., Takeuchi, T. Atrazine-selective Polymer Prepared by Molecular Imprinting Technique, Chem. Lett. 1995, 489.

[142] Kugimiya, A., Matsui, J.,Takeuchi, T.,Yano, K., Muguruma, H.,Elgersma, A. V., Karube, I. Recognition of Sialic Acid Using Molecularly Imprinted Polymer, Anal. Lett. 1995, 28, 2317-2323.

[143] Matsui, J., Kato, T. Takeuchi, T., Suzuki, M., Yokoyama, K., Tamiya, E., Karube, I. Molecular Recognition in Continuous Polymer Rods Prepared by a Molecular Imprinting Technique, Anal. Chem. 1993, 65, 2223-4.

(2)バイオセンサーに関する研究(Biosensors)

[144] Takano, E., Shimura, N., Ujima, Y., Sunayama, H, Kitayama, Y., Takeuchi, T. Highly sensitive fluoro-immunosensing for biomarker detection using an automatic pipette tip-type biosensing system, ACS Omega 2019, 4 (1), 1487-1493.

[145] Takano, E., Shimura, N., Akiba, T., Kitayama, Y., Sunayama, H., Abe, K., Ikebukuro, Takeuchi, T. Pipette tip biosensors for bacterial double-stranded DNA using bioluminescence induced by zinc finger luciferase, Microchim. Acta 2017, 184, 1595-1601.

Ooya, T., Sakata, Y., Choi, H. W., Takeuchi, T. Reflectometric interference spectroscopy-based sensing for evaluating biodegradability of polymeric thin films, Acta Biomater. 2016, 38, 163-167.

[146] Choi, H. W, Sakata, Y., Ooya, T., Takeuchi, T. Reflectometric Interference Spectroscopy-based Immunosensing Using Immobilized Antibody via His-tagged Recombinant Protein A J. Biosci. Bioeng.. 2015, 119, 195-199.

[147] Kurihara, Y., Sawazumi, T., Takeuchi, T. Exploration of interactions between membrane proteins embedded in supported lipid bilayers and their antibodies by reflectometric interference spectroscopy-based sensing, Analyst 2014, 139, 6016-6021.

[148] Murata, A., Ooya, T., Takeuchi, T. Two-Layer Reflectometric Interference Spectroscopy-Based Immunosensing for C-Reactive Protein, Microchim. Acta 2014, 182, 307-313.

[149] Murata, A., Ooya, T., Takeuchi, T. Simple immobilization of antibody in organic/inorganic hybrid thin films for immunosensing, Biosens. Bioelectron. 2013, 43, 45-49.

[150] Kurihara, Y., Takama, M., Masubuchi, M., Ooya, T., Takeuchi, T. Microfluidic Reflectometric Interference Spectroscopy-based Sensing for Exploration of Protein-Protein Interaction Conditions, Biosens. Bioelectron. 2013, 40, 247-251.

[151] Kurihara, Y., Takama, M., Sekiya, T., Yoshihara, Y., Ooya, T., Takeuchi, T. Fabrication of Carboxylated Silicon Nitride Sensor Chips for Detection of Antigen-Antibody Reaction Using Microfluidic Reflectometric Interference Spectroscopy, Langmuir 2012, 28, 13609-13615.

[152] Choi, H. G., Kurihara, Y., Ooya, T., Takeuchi, T. Label-free Detection of C-reactive Protein Using Reflectometric Interference Spectroscopy-based Sensing System, Anal. Chim. Acta 2012, 728, 64-68.

[153] Choi, H. G., Takahashi, H., Ooya, T., Takeuchi, T. Label-free Detection of Glycoproteins Using Reflectometric Interference Spectroscopy-Based Sensing System with Upright Episcopic Illumination, Anal. Methods 2011, 3, 1366-1370.

[154] Ikebukuro, K., Wakamaru, K., Karube, I., Kubo, I., Inagawa, M., Sugawara, T., Arikawa, Y., Suzuki, M., Takeuchi, T., Phosphate Sensing System Using Pyruvate Oxidase and Chemiluminescence Detection, Biosens. Bioelectron. 1996, 11, 959-965.

[155] Ikebukuro, K., Nishida, R., Yamamoto, H., Arikawa, Y., Nakamura, H., Suzuki, M., Kubo, I., Takeuchi, T., Karube, I. A novel biosensor system for the determination of phosphate, J. Biotechnol. 1996, 48, 67-72.

[156] Mitsubayashi, M., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. Monitoring Sweat Lactate, Trans. Mat. Res. Soc. Jpn. 1994, 15A, 429-432.

[157] Mitsubayashi, K., Dicks, J. M., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. A Flexible Biosensor for Glucose, Electroanalysis 1995, 7, 83-87.

[158] Mitsubayashi, K., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. Monitoring of Sweat Lactate, Trans. Mater. Res. Soc. Jpn. 1994, 15A, 429-432.

[159] Mitsubayashi, K., Ogasawara, K., Yokoyama, K., Takeuchi, T., Tsuru T., Karube, I. Measurement of Tear Electrolyte Concentration and Turnover Rate Using a Flexible Conductimetric Sensor, Technol. Health Care 1995, 3, 117-121.

[160] Yokoyama, S., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. Urobilin Measurement Based on Peroxyoxalate Chemiluminescence, Trans. Mater. Res. Soc. Jpn. 1994, 15A, 433-436.

[161] Kubo, I., Karube, I., Takeuchi, T., Furusawa, M., Arikawa, Y., Kanagawa, T. A Biosensor Based on Thiobacillus thioparus for Measuring Thiosulfate and Methanethiol, Can. J. Microbiol. 1995, 41, 366-371.

[162] Imai, S., Suzuki, M., Takeuchi, T., Tamiya, E., Karube, I. Total Protein Sensor Based on Piezoelectric Quartz Crystal, Anal. Chim. Acta 1994, 292, 65-70.

[163] Yokoyama, K., Sasaki, S., Ikebukuro, K., Takeuchi, T., Karube, I., Tokitsu, Y., Masuda, Y. Biosensing Based on NADH Detection Coupled to Electrogenerated Chemiluminescence from Ruthenium Tris (2,2'-Bipyridine), Talanta 1994, 41, 1035-1040.

[164] Nomura, Y., Ikebukuro, K., Yokoyama, K., Takeuchi, T., Arikawa, Y., Ohno, S., Karube, I. A Novel Microbial Sensor for Anionic Surfactant Determination, Anal. Lett. 1994, 27, 3095-3108.

[165] Murakami, Y., Uchida, T., Takeuchi, T., Tamiya, E., Karube, I., Suda, M. Micromachined Electrochemical Flow Cell for Biosensing, Electroanalysis 1994, 6, 735-739.

[166] Murakami, Y., Suda, M., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. Micromachined Enzyme Reactor for FIA System, Microchem. J. 1994, 49, 319-325.

[167] Mitsubayashi, K., Yokoyama, K., Takeuchi, T., Karube, I. Gas-Phase Biosensor for Ethanol, Anal. Chem. 1994, 66, 3297-3302.

[168] Mitsubayashi, K., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. Flexible Conductimetric Sensor, Anal. Chem. 1993, 65, 3586-3590.

[169] Murakami, Y., Takeuchi, T., Yokoyama, K., Tamiya, E., Karube, I, Suda, M. Integration of Enzyme-immobilized Column and Electrochemical Flow Cell Using Micromachining Techniques for the Glucose Detection System, Anal. Chem. 1993, 65, 2731-2735.

[170] Tamiya, E., Sugiura, Y., Akiyama, A., Suzuki, M., Takeuchi, T. and Karube, I. Ultra-Micro Glutamate Sensor Using Platinized Carbon Fiber Electrode Integrated Counter Electrode, Sensors and Actuators 1993, B10, 179-184.

[171] Navera, E. N., Suzuki, M., Takeuchi, T., Tamiya, E., Karube, I. Nafion-Coated Carbon Fiber for Acetylcholine and Choline Sensors, Electroanalysis 1993, 5, 17-22.

[172] Navera, E. N., Yamashita, J., Suzuki, M., Yokoyama, K., Tamiya, E., Takeuchi, T., Karube, I. Micro-Choline Sensor for Acetylcholinesterase Determination, Anal. Chim. Acta 1993, 281, 673-679.

[173] Hyun, C. K., Tamiya, E., Takeuchi, T., Karube, I. A Novel BOD Sensor Based on Bacterial Luminescence, Biotechnol. Bioeng. 1993, 41, 1107-1111.

[174] Yokoyama, K., Nakajima, K., Uchiyama, S., Suzuki, S., Suzuki, M., Takeuchi, T., Tamiya, E., Karube, I Mediated Micro Glucose Sensors Using 2 mm Platinum Electrode, Electroanalysis 1992, 4, 859-864.

[175] Iwasaki, Y., Suzuki, M., Takeuchi, T., Tamiya, E., Karube, I., Nishiyama, M., Horinouchi, S., Beppu, T., Kadoi, H., Uchiyama, S., Suzuki, S. Direct Electron Transfer Reaction of a Blue Protein from Alcaligenes faecalis Strain-6, Electroanalysis 1992, 4, 756-770.

[176] Iwasaki, Y., Takeuchi, T., Tamiya, E., Karube, I., Nishiyama, M., Horinouchi, S., Beppu, T., Kadoi, H., Uchiyama, S., Suzuki, S., M. Electrocatalysis of Nitrate Reductase from Alcaligenes faecalis S-6 Mediated by Native Redox Partner, Electroanalysis 1992, 4, 771-776.

(3)非放射性レセプターアッセイによる薬物の定量法に関する研究(Non-isotopic receptor assays for drug quantification)

[177] Takeuchi, T., Nishikawa, T., Matsukawa, R., Matsui, J. Non-isotopic Receptor Assay for Benzodiazepine drugs Using Time-resolved Fluorometry, Anal. Chem. 1995, 67, 2655-2658.

[178] Takeuchi, T., Yoshida, M., Kabasawa, Y., Matsukawa, R., Tamiya, E., Karube, I. Time-resolved Fluorometric Receptor Assay for Benzodiazepines, Anal. Lett. 1993, 26, 1535-1545.

[179] Takeuchi, T., Tanaka, S., Rechnitz, G. A. A Biotinylated-1012S Conjugate as a Probe Ligand for Benzodiazepine Receptors: Characterization of Receptor Binding Site and Receptor Assay for Benzodiazepine Drugs, Anal. Biochem. 1992, 203, 158-162.

[180] Chen, L., Takeuchi, T., Rechnitz, G. A. Development of a Nonisotopic Acetylcholine Receptor Assay for the Investigation of Cholinergic Ligands, Anal. Chim. Acta 1992, 267, 55-62.

[181] Tanaka, S., Takeuchi, T., Rechnitz, G. A. Non-Isotopic Receptor Assay for Benzodiazepines Using a Biotin-labeled Ligand and Biotin Immobilized Microtiter Plate, J. Chromatogr. 1992, 597, 443-448.

[182] Takeuchi, T., Tanaka, S., Rechnitz, G. A. Non-Isotopic Receptor Assay for Benzodiazepine Drugs Using Biotin-Benzodiazepine Conjugate, Anal. Lett. 1991, 24, 2111-2121.

[183] Takeuchi, T., Rechnitz, G. A. Nonisotopic Receptor-Binding Assay for Benzodiazepine Receptors Utilizing a Fluorophore Labeled Ligand, Anal. Biochem. 1991, 194, 250-255.

[184] Takeuchi, T., Tham, S. Y., Rechnitz, G. A. Biotin Binding Assay Utilizing Avidin- Peroxidase Conjugate and Immobilized Iminobiotin on Polystyrene Beads, Anal. Chim. Acta 1991, 251, 291-295.

[185] Takeuchi, T. and Rechnitz, G. A. Enzymatic Solid-Phase Assay for Biotin and a Biotin-Benzodiazepine Conjugate, Bioconjugate Chem. 1990, 1, 227-230.

(4)生体関連物質の計測(バイオセンサーを除く)に関する研究(Measurement of biologically relevant substances (excluding biosensors))

[186] Song, M. I., Iwata, K., Yamada, M., Yokoyama, K., Takeuchi, T., Tamiya, E., Karube, I. Multisamples Analysis Using an Array of Microreactors for an Alternating-Current Field-Enhanced Latex Immunoassay, Anal. Chem. 1994, 66, 778-781.

[187] Sekine, Y., Suzuki, M., Takeuchi, T., Tamiya, E. and Karube, I. Highly Sensitive Methanol Determination System Based on Chemiluminescence Using Flow Injection Analysis, Anal. Chim. Acta 1993, 280, 179-184.

[188] Takeuchi, T., Kabasawa, Y., Horikawa, R. and Tanimura, T. Mechanized Assay of Serum Cholinesterase Activity by Specific Colorimetric Detection of Released Acid, Clin. Chim. Acta 1992, 205, 117-126.

[189] Takeuchi, T., Kabasawa, Y. and Tanimura, T. Continuous Separation of Lanthanides by Countercurrent Fractional Extraction, J. Chromatogr. 1991, 538, 125-131.

[190] Takeuchi, T., Kabasawa, Y., Horikawa, R. and Tanimura, T. Flow Injection Determination of Drugs by Specific Detection of Carboxylic Acids, Analyst 1988, 113, 1673-1675.

[191] Takeuchi, T., Kabasawa, Y., Horikawa, R. and Tanimura, T. Automated Assay of Serum Cholinesterase Activity, J. Pharm. Sci., 1987, 76, S4.

[192] Takeuchi, T., Horikawa, R. and Tanimura, T. Spectrophotometric Determination of Carboxylic Acids by Ferric Hydroxamate Formation with Water-Soluble Carbodiimide, Anal. Lett. 1980, 13 (A7), 603-609.

(5)マリンバイオテクノロジーに関する研究(Marine biotechnology)

[193] Matsukawa, R., Dubinsky, Z., Masaki, K., Takeuchi, T., Karube, I. Enzymatic Screening of Macroalgae as a Potential Source of Natural Antioxidants, Appl. Biochem. Biotechnol. 1997, 66, 239-247.

[194] Matsukawa, R., Dubinsky, Z., Kishimoto, E., Masaki, K., Masuda, Y., Takeuchi, T., Chihara, M., Yamamoto, Y., Niki, E., Karube, I. A Comparison of Screening Methods for Antioxidant Activity in Seaweeds, J. Appl. Phycol. 1997, 9, 29-35.

[195] Lee, T.-Y., Gotoh, N., Niki, E., Yokoyama, K., Tsuzuki, M., Takeuchi, T., Karube, I. Chemiluminescence Detection of Red Tide Phytoplankton Chattonella marina, Anal. Chem. 1995, 67, 225-228.

[196] Lee, T.-Y., Tsuzuki, M., Takeuchi, T., Yokoyama, K., Karube, I. Quantitative Determination of Cyanobacteria in Mixed Phytoplankton Assemblages by an in vivo Fluorimetric Method, Anal. Chim. Acta 1995, 302, 81-87.

[197] Lee, T.-Y., Tsuzuki, M., Takeuchi, T., Yokoyama, K., Karube, I. In vivo Fluorometric Method for Early Detection of Cyanobacterial Waterblooms, J. Appl. Phycol. 1994, 6, 489-495.

[198] Takeuchi, T., Yokoyama, K., Imai, O., Masuda, Y., Utsunomiya, K., Kobayashi, K., Suzuki, M., Tamiya, E., Karube, I. Photosynthetic Activity Sensor Based on Oxygen Electrode Integrated with Optical Fibers, Anal. Chim. Acta 1993, 276, 65-68.

[199] Hanagata, N., Ito, A., Uehara, H., Asari, F., Takeuchi, T., Karube, I. Behavior of Cell Aggregate of Carthamus tinctorius L. Cultured Cell and Correlation with Red Pigment Formation, J. Biotechnol. 1993, 30, 259-269.

[200] Hanagata, N., Uehara, H., Ito, A., Takeuchi, T., Karube, I. Elicitor for Red Pigment Formation in Carthamus tinctorius Cultured Cells, J. Biotechnol. 1994, 34, 71-77.

[201] Takeuchi, T., Utsunomiya, K., Kobayashi, K., Owada, M., Karube, I. Carbon Dioxide Fixation by a Unicellular Green Alga Oocystis sp., J. Biotechnol. 1992, 205, 117-126.

[202] Hanagata, N., Takeuchi, T., Fukuju, Y, Barnes, D. J., Karube, I. Tolerance of Microalgae to High CO2 and High Temperature, Phytochemistry 1992, 31, 3345-3348.

(6)生体関連光学異性体の分離・分析に関する研究(Separation and analysis of biologically relevant optical isomers)

[203] Takeuchi, T., Yamazaki, S., Tanimura, T. Enantioselective Solubilization of DL-Amino Acids in Organic Solvents Containing N-n-Alkyl-L-Proline and Copper(II) Ions, Anal. Chim. Acta 1991, 242, 291-294.

[204] Yamazaki, S., Takeuchi, T., Tanimura, T. Direct Enantiomeric Separation of b-Amino Acids and b-Amino Alcohols by Ligand-Exchange Chromatography, J. Chromatogr. 1991, 540, 169-175.

[205] Takeuchi, T., Horikawa, R., Tanimura, T., Kabasawa, Y. Resolution of DL-Valine by Countercurrent Solvent Extraction with Continuous Sample Feeding, Sep. Sci. Technol. 1990, 25, 941-951.

[206] Yamazaki, S., Takeuchi, T., Tanimura, T. Direct Enantiomeric Separation of Norephedrine and Its Analogues by High-Performance Liquid Chromatography, J. Liq. Chromatogr. 1989, 12, 2239-2248.

[207] Takeuchi, T., Horikawa, R., Tanimura, T. Enantioselective Solvent Extraction of Neutral DL-Amino Acids in Two-Phase Systems Containing N-n-Alkyl-L-Proline Derivatives and Copper(II) Ions, Anal. Chem. 1984, 56, 1152-1155.

[208] Takeuchi, T., Horikawa, R., Tanimura, T. Complete Resolution of DL-Isoleucine by Droplet Countercurrent Chromatography, J. Chromatogr. 1984, 284, 285-288.

著書・総説(Books・review articles)

[209] 週刊 医学のあゆみ 2024, 291(9) 749-755.

[210] 新訂三版 ラジカル重合ハンドブック(2023)澤本光男監修、第4編、第2章、第1節(NTS)

[211] 北山、竹内「精密分子認識空間構築を実現する配向性分子インプリンティング」分析化学 2019, 68 (2), 89-101.

[212] 砂山、竹内「分子インプリンティングによる高感度分子認識素子の開発とその応用」ファルマシア 2019, 55 (2), 150-154.

[213] Takeuchi, T., Sunayama, H., Beyond natural antibodies - a new generation of synthetic antibodies created by post-imprinting modification of molecularly imprinted polymer, Chem. Commun. 2018, 54, 6243-6251 (Feature article).

[214] Takeuchi, T., Hayashi, T., Ichikawa, S., Kaji, A., Masui, M., Matsumoto, H., Sasao, R. Molecularly imprinted tailor-made functional polymer receptors for highly sensitive and selective separation and detection of target molecules, Chromatography 2016, 37, 43-64. (Open Access)

[215] 竹内, 砂山,【総合論文】 分子インプリンティングの新展開-ポストインプリンティング修飾による分子インプリント材料の多機能化, 高分子論文集 2016, 73, 19-29.

[216] Takeuchi, T, Sunayama, H., Takano, E., Kitayama, Y. Post-imprinting and in-cavity functionalization, In: Mattiasson, B., Ye, L. Eds. Molecularly Imprinted Polymers in Biotechnology (a series of Advances in Biochemical Engineering/Biotechnology), Springer (Heidelberg) pp 95-106 (2015).

[217] Takeuchi, T, Sunayama, H. Molecularly Imprinted Polymers, In: Kobayashi, S., Mullen, K. Eds. Encyclopedia of Polymeric Nanomaterials, Springer-Verlag Berlin Heidelberg, article 126-1, pp 1-5 (2014).

[218] Takeuchi, T. Protein-sensing using organic/inorganic hybrid materials prepared by liquid-phase deposition-based molecular imprinting, In: Lee, S-W, Kunitake T. Handbook of Molecular Imprinting, Pan Stanford Publishing Pte Led. pp 487-497 (2013).

[219] Takeuchi, T., Hishiya, T. Molecular Imprinting of Proteins Emerging as a Tool for Protein Recognition, Org. Biomol. Chem., 2008, 6, 2459-2467.

[220] M. Komiyama, T. Takeuchi, T. Mukawa, H. Asanuma, "Molecular Imprinting", WILEY-VCH, Weinheim, 2002.

[221] Matsui, J., Takeuchi, T. Techniques for the In Situ Preparation of Imprinted Polymers, In Molecularly Imprinted Polymers: Man made Mimics of Antibodies and Their Application in Analytical Chemistry, Sellergren, B. Ed., Elsevier, pp. 325-340, 2001.

[222] Takeuchi, T., Shionoya, M. Synthetic Receptors Prepared by Organized Assembly of Organic Molecules, IEEE EMB magazine, 2002, 21 (6), 144-150.

[223] Takeuchi, T., Haginaka, J. Separation and Sensing Based on Molecular Recognition Using Molecularly Imprinted Polymers, J. Chromatogr. B 1999, 728, 1-20.

[224] Takeuchi, T., Matsui, J. Recognition of Drugs and Herbicides: Strategy in Selection of Functional Monomers in Non-covalent Molecular Imprinting, in Molecular and Ionic Recognition with Imprinted Polymers, ACS Symp. Series 703, ACS Publications, Washington, DC, 1998, pp. 119-134.

[225] Takeuchi, T., Matsui, J. Molecular imprinting: an approach to "tailor-made" synthetic polymers with biomimetic functions (Feature Article), Acta Polymer 1996, 47. 471-480.

[226] Karube, I., Takeuchi, T. and Barnes, D. J. Biotechnological Reduction of CO2 Emissions, Adv. Biochem. Eng. Biotechnol. 1992, 46, 63-79.

[227] 砂山博文, 竹内俊文「分子インプリント高分子の蛍光センシングの応用」高分子 2012, 61, 406-409.

[228] 竹内俊文 「モレキュラーインプリンティング」ラジカル重合ハンドブック, 蒲池幹治, 遠藤剛, 岡本佳男, 福田猛 監修 2010, 第4編, 第2章, 第2節(NTS)

[229] 竹内俊文, 大谷亨 「モレキュラーインプリント法による人工酵素」酵素利用技術大系, 小宮山眞監修, 2010, 第4編, 第6節(NTS).

[230] 竹内俊文 「分子インプリンティングのバイオ応用」ナノ空間材料の創製と応用, 有賀克彦編 2009, 第5章, 第5節(フロンティア出版)

[231] 大谷 亨, 竹内俊文「モレキュラーインプリンティング -最近の展開-」高分子 2008, 57, 903-911.

[232] 竹内俊文「モレキュラーインプリンティングによるタンパク質認識材料の創製」Electrochemistry(電気化学および工業物理化学) 2007, 75. 986-991.

[233] 竹内俊文, 菱谷隆行, 松井 淳「分子インプリント材料を分子素子として用いたセンサー」バイオセンサーの先端科学技術と応用, 民谷栄一監修 2007, 8章 (シーエムシー出版).

[234] 竹内俊文, 新森英之「分子インプリントポリマーを用いたセンシング」バイオセンサ・ケミカルセンサ事典, 軽部征夫編 2007, 2章 第5節-2 (テクノシステム).

[235] 竹内俊文 「高分子プローブとしてのモレキュラーインプリントポリマー」, 高分子 2003, 52, 458-461.

[236] 竹内俊文 「モレキュラーインプリンティング」 生命科学のニューセントラルドグマ, 杉本直己編 2002, 19章.

[237] 竹内俊文, 「モレキュラーインプリンティングによる分子認識材料の創製」, バイオサイエンスとインダストリー 2000, 58, 17-22.

[238] 竹内俊文 「モレキュラーインプリンティング」 ラジカル重合ハンドブック, 蒲池幹治・遠藤剛監修(エヌ・ティー・エス), pp. 645-654, 1999.

[239] 竹内俊文, 久保裕之 モレキュラーインプリントアフィニティ材料, ぶんせき, 1998, No. 11, 840-846.

[240] 松井. 竹内 「モレキュラーインプリンティング-人工アフィニティ材料の創製-」化学と工業 1997, 50, 597-598.

[241] 竹内 「レセプターを用いる薬物の定量-天然及び人工レセプターを利用して-」臨床化学 1997, 26, 1-6.

[242] 竹内 「モレキュラーインプリンティング-分子情報を人工高分子内に刷り込む-」蛋白質核酸酵素 1997, 42, 1320-1326.

[243] 釘宮章光、松井淳、竹内俊文「モレキュラーインプリンティングによるテーラーメイド分子認識ポリマーの合成」酵素工学ニュース 1996 (35), 6-9.

[244] 松井淳, 竹内俊文「テーラーメイド分子認識ポリマー」化学と工業 1995, 48, 1259-1261.

[245] 竹内俊文, 村上裕二「酵素センサー」膜学実験シリーズ第2巻生体機能類似膜編(日本膜学会編)pp 180-190, 1994.

[246] 竹内俊文「細胞、オルガネラ、組織を用いるセンサー」膜学実験シリーズ第2巻生体機能類似膜編(日本膜学会編)pp 209-214, 1994.

[247] 竹内俊文, 軽部征夫「非放射性レセプターアッセイの開発」化学 1993, 48, 578-579.

[248] 軽部征夫, 竹内俊文「マイクロマシン技術を応用した集積型フローインジェクション分析システム」化学 1992, 47, 434-435.

[249] 竹内俊文「IMBC '91 国際会議」酵素工学ニュース 1992, 27, 36.

[250] 竹内俊文「ハワイのハイテク事情」化学と工業 1991, 44, 688-689.