KEIO RESEARCHERS INFORMATION SYSTEM

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士（学術）, Kyushu Institute of Technology, Coursework, 2007.03

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Neuroscience-general

• Life Science / Pharmacology

• Life Science / Biomedical engineering

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Neuroscience

• ダイヤモンド電極

• 神経科学

Books 【 Display / hide 】

Books 【 Display / hide 】

• Diamond electrodes : fundamentals and applications

  Ogata G, Sawamura S, Asai K, Kusuhara H, Einaga Y, Hibino H, Springer, 2022.03

  Scope: In Vivo Real-Time Measurement of Drugs.,  Contact page： 227-236

  　View Summary

  Drugs play a key role in the treatment of patients with various diseases. A compound, when administered systemically, shows differential spatial and temporal distribution patterns not only in the body but also within each organ. In response to an increase or decrease in local concentrations in the organ, the activity of the cell population expressing the drug’s target protein(s) changes over time. Therefore, real time, simultaneous detection of kinetics of the drug and its pharmacological effects in in vivo microenvironments is essential for evaluating the efficacy of medicines. Although such challenging dual-mode measurement has not yet been addressed by any conventional methods, it has been successfully achieved via a microsensing system that we recently developed. The system consists of two different sensors: A needle-type boron-doped diamond microelectrode for monitoring the drug and a glass microelectrode for tracking electrophysiological activity of the target cells. This state-of-the-art approach is applicable to various drugs in terms of “local” pharmacokinetic and pharmacodynamic assays in vivo and may contribute to the development of next-generation therapeutic interventions.

  • Access to Document (DOI)

• Involvement of the intracellular Ca²⁺/calmodulin kinase activation network in the induction of bicuculline-induced epileptic discharges in hippocampal slices, and the brain informatics simulator “HIPPO-STATION”

  Ogata, G. and Yoshimatsu, S. and Natsume, K., 2004

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• A strategy for low-cost portable monitoring of plasma drug concentrations using a sustainable boron-doped-diamond chip

  Takuro Saiki, Genki Ogata, Seishiro Sawamura, Kai Asai, Olga Razvina, Kota Watanabe, Rito Kato, Qi Zhang, Koei Akiyama, Sasya Madhurantakam, Norzahirah Binti Ahmad, Daisuke Ino, Haruma Nashimoto, Yoshifumi Matsumoto, Masato Moriyama, Arata Horii, Chie Kondo, Ryosuke Ochiai, Hiroyuki Kusuhara, Yasuo Saijo, Yasuaki Einaga, Hiroshi Hibino

  Heliyon （Elsevier BV)  9 （ 5 ） e15963 - e15963 2023.05

  Accepted,  ISSN  2405-8440

  　View Summary

  On-site monitoring of plasma drug concentrations is required for effective therapies. Recently developed handy biosensors are not yet popular owing to insufficient evaluation of accuracy on clinical samples and the necessity of complicated costly fabrication processes. Here, we approached these bottlenecks via a strategy involving engineeringly unmodified boron-doped diamond (BDD), a sustainable electrochemical material. A sensing system based on a ∼1 cm2 BDD chip, when analysing rat plasma spiked with a molecular-targeting anticancer drug, pazopanib, detected clinically relevant concentrations. The response was stable in 60 sequential measurements on the same chip. In a clinical study, data obtained with a BDD chip were consistent with liquid chromatography–mass spectrometry results. Finally, the portable system with a palm-sized sensor containing the chip analysed ∼40 μL of whole blood from dosed rats within ∼10 min. This approach with the ‘reusable’ sensor may improve point-of-monitoring systems and personalised medicine while reducing medical costs.

  • Access to Document (DOI)

• Calcium/calmodulin-dependent protein kinase II associates with the K+ channel isoform Kv4.3 in adult rat optic nerve

  Genki Ogata, Gloria J. Partida, Anna Fasoli, Andrew T. Ishida

  Frontiers in Neuroanatomy （Frontiers Media SA)  16 2022.09

  Lead author, Accepted,  ISSN  16625129

  　View Summary

  Spikes are said to exhibit “memory” in that they can be altered by spikes that precede them. In retinal ganglion cell axons, for example, rapid spiking can slow the propagation of subsequent spikes. This increases inter-spike interval and, thus, low-pass filters instantaneous spike frequency. Similarly, a K⁺ ion channel blocker (4-aminopyridine, 4AP) increases the time-to-peak of compound action potentials recorded from optic nerve, and we recently found that reducing autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) does too. These results would be expected if CaMKII modulates spike propagation by regulating 4AP-sensitive K⁺ channels. As steps toward identifying a possible substrate, we test whether (i) 4AP alters optic nerve spike shape in ways consistent with reducing K⁺ current, (ii) 4AP alters spike propagation consistent with effects of reducing CaMKII activation, (iii) antibodies directed against 4AP-sensitive and CaMKII-regulated K⁺ channels bind to optic nerve axons, and (iv) optic nerve CaMKII co-immunoprecipitates with 4AP-sensitive K⁺ channels. We find that, in adult rat optic nerve, (i) 4AP selectively slows spike repolarization, (ii) 4AP slows spike propagation, (iii) immunogen-blockable staining is achieved with anti-Kv4.3 antibodies but not with antibodies directed against Kv1.4 or Kv4.2, and (iv) CaMKII associates with Kv4.3. Kv4.3 may thus be a substrate that underlies activity-dependent spike regulation in adult visual system pathways.

  • Access to Document (DOI)

• A rapid and simple electrochemical detection of the free drug concentration in human serum using boron-doped diamond electrodes

  HIdeto Moriyama, Genki Ogata, Haruma Nashimoto, Seishiro Sawamura, Yoshiaki Furukawa, Hiroshi Hibino, Hiroyuki Kusuhara, Yasuaki Einaga

  The Analyst （Royal Society of Chemistry (RSC))  147 （ 20 ） 4442 - 4449 2022.09

  Lead author, Accepted,  ISSN  0003-2654

  　View Summary

  Monitoring drug concentration in the blood and reflecting this in the dosage is crucial for safe and effective drug treatment. Most drug assays are based on total concentrations of bound...

  • Access to Document (DOI)

• Electrochemical detection of triamterene in human urine using boron-doped diamond electrodes

  Kanako Ishii, Genki Ogata, Yasuaki Einaga

  Biosensors and Bioelectronics （Elsevier BV)  217   114666 - 114666 2022.09

  Accepted,  ISSN  0956-5663

  　View Summary

  Urine is one of the most used biological fluids for screening drug delivery and the resultant metabolites. In sports, the use of diuretics such as triamterene is considered a violation of anti-doping rules and is stipulated to be present at less than 79 nM in urine by the World Anti-Doping Agency (WADA). It is therefore important to develop effective rapid and low-cost tests for this diuretic. Here we apply electrochemical analysis using boron-doped diamond (BDD) electrodes, which have superior properties such as low background current, a wide potential window, and high resistance to deactivation. Since real urine samples show clear oxidation current peaks in the potential range more positive than 0.5 V (vs. Ag/AgCl) due to the presence of bio-components such as protein, uric acid, and ascorbic acid, to detect triamterene effectively, the electrochemical protocol was optimized towards a potential range where the other components have limited effect. Our results show that reduced triamterene exhibits an oxidation peak at 0.1 V (vs. Ag/AgCl) in 0.1 M phosphate buffer (PB) and at 0.2 V (vs. Ag/AgCl) in pooled human urine. The peak current value increased according to the triamterene concentration. The limit of detection (LOD) was 3.15 nM in the PB and 7.80 nM in pooled human urine. Finally, triamterene detection was attempted in individual urine samples. Triamterene was electrochemically detectable in individual urine samples, excluding urine samples containing an excess amount of ascorbic acid. The limit of detection (LOD) in individual urine samples was determined to be 20.8 nM.

  • Access to Document (DOI)

• Application of boron doped diamond electrodes to electrochemical gas sensor

  Yunita Triana, Genki Ogata, Yasuaki Einaga

  Current Opinion in Electrochemistry （Elsevier BV)  36   101113 - 101113 2022.08

  Accepted,  ISSN  2451-9103

  　View Summary

  Boron-doped diamond (BDD) electrodes have been attracting attention as superior electrode materials for electrochemical sensing applications. Here, we focused on applications of the BDD electrodes to electrochemical gas sensing especially dissolved gas in aqueous solution. This article discusses arsine, hydrogen sulfide, nitrogen dioxide gas for environmental sensing, and oxygen in the blood for biomedical sensing. The analytical performances suggest that BDD electrodes are more than adequate for determining the concentration of these gas species.

  • Access to Document (DOI)

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Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• ダイヤモンド電極による緑内障点眼薬の電気化学リアルタイム計測

  栄長 泰明, 米田 真央, 緒方 元気, 山岸 麗子, 本庄 恵, 相原 一

  日本眼薬理学会プログラム・抄録集 (日本眼薬理学会)  42回   63 - 63 2022.10

• 研究者の最新動向　針状ダイヤモンド電極を駆使した脳の薬物モニタリングシステムの創出

  澤村 晴志朗, 緒方 元気, 栄長 泰明, 日比野 浩

  Precision Medicine ((株)北隆館)  5 ( 7 ) 645 - 647 2022.07

  ISSN  2434-3625

  　View Summary

  てんかんは最も高頻度に起こる神経疾患の1つである。その治療の中心は薬物であるが、重い副作用が生じる例も少なくない。深刻な問題は、薬効と副作用が個人で異なることである。患者1人ひとりに合った投薬の設計には、その基礎段階として、モデル動物を用い、全身に投与した薬が標的となる脳の局所でどのように振る舞い、それに応じていかに薬効が変化するかを、リアルタイムかつ定量的に捉える研究が必要である。この困難な課題にアプローチするため、針状ダイヤモンド電極を搭載した薬物計測システムを開発した。(著者抄録)

• ダイヤモンド電極を用いた電気化学測定による薬物血中濃度の迅速測定

  齋木琢郎, 齋木琢郎, 緒方元気, 澤村晴志朗, ラズビナ オリガ, 渡邊航太, 加藤里都, 浅井開, 松本吉史, 森山雅人, 西條康夫, 楠原洋之, 栄長泰明, 日比野浩

  日本生理学雑誌(Web) ((一社)日本生理学会)  83 ( 2 ) 25 - 26 2021

  ISSN  0031-9341

• A strategy for rapid and easy measurement of plasma concentration of pazopanib

  緒方元気, 齋木琢郎, 齋木琢郎, 澤村晴志朗, RAZVINA Olga, 渡邉航太, 加藤理都, 浅井開, 花輪藍, 松本吉史, 森山雅人, 西條康夫, 楠原洋之, 栄長泰明, 日比野浩

  日本生体医工学会大会プログラム・抄録集(Web) 60th 2021

• がんオーダーメイド治療に貢献するポータブル血中「薬物」濃度測定器の創出

  緒方 元気, 椎木 弘, 高井 まどか, 楠原 洋之, 栄長 泰明, 日比野 浩

  福田記念医療技術振興財団情報 ((公財)福田記念医療技術振興財団)   ( 33 ) 97 - 104 2020.12

  　View Summary

  最先端素材ダイヤモンドセンサを駆使した電気化学的測定法によりポータブル血中「薬物」濃度測定器を創出し、その基礎実験を行った。ラット血漿にパゾパニブを添加して検証したところ、100μL血漿から推奨濃度域をカバーする0〜150μMの範囲を測定可能であった。次にパゾパニブを経口投与したラットから採血し、血漿中濃度の時間経過を検討したところ、tmaxは〜4時間となり、先行研究で得られた薬物動態の結果と類似していた。本測定法は約35秒の短時間で、サンプル処理を含めても全行程が10分以内で完了したことから、がんオーダーメイド治療に貢献できる可能性が示唆された。

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

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

• ダイヤモンド電極法を用いた血中薬物濃度測定に基づくパゾパニブ服用患者の観察研究

  2022.04

  -

  2025.03

  日本学術振興会, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Coinvestigator(s)

  　View Summary

  現在，血漿サンプル量: ~100 µL，測定時間: ~35秒，簡単なボタン操作のみで測定可能な系を確立した．今後，動物血漿検体を用い，迅速性，簡便性，測定感度のさらなる向上を目指し，電極装置，サンプル処理法などの最適化を進める．
  また，実臨床で薬剤を服用予定の患者に，文書による同意を得た上で採血を行い，本手法による血中薬物濃度測定が可能であるか，測定結果が妥当であるか，検証を行う．

• 針状ダイヤモンドセンサを用いたノンラベリング緑内障点眼薬のリアルタイムin vivo測定法の創出

  2022

  -

  2027

  公益財団法人 武田科学振興財団, 2022年度ライフサイエンス研究助成, Principal investigator

• がんオーダーメイド治療に貢献するダイヤモンドセンサを用いた血漿中の分子標的薬の迅速測定法の開発

  2022

  -

  2023

  公益財団法人 持田記念医学薬学振興財団, 2022年度 研究助成金, Principal investigator

• 極微量血液からのポータブル迅速薬物測定システムの創出

  2022

  -

  2023

  公益財団法人内藤記念科学振興財団, 第 54 回(2022 年度) 内藤記念科学奨励金・研究助成, Principal investigator

• Development of a handy system for rapid drug monitoring from tiny amounts of blood

  2021.04

  -

  2024.03

  Niigata University, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Research grant, Principal investigator

  　View Summary

  安心・安全な薬物療法を実施するためには、血中の薬物濃度と薬の効果や副作用を観察しながら投薬量をコントロールする必要がある。しかしながら、現在、多くの処方薬において臨床の現場で簡単、迅速に測定できる装置が存在せず、治療薬物モニタリングが困難な状況である。以上を踏まえ、本研究では、極微量の血液から薬の濃度を「その場で瞬時に」測定するハンディシステムの創出を目指している。
  本年度は、利尿薬トリアムテレン、抗がん剤であるドキソルビシンや分子標的薬パゾパニブを測定象薬物とし、それらをダイヤモンド電極センサにて感度良く計測するため、最適なサンプルの前処理方法や電気化学測定法を探索した。さらに、これらの薬を尿中や血漿中に溶解したサンプルを作成し、測定可能であるか検証した。
  検討の結果、これらの薬物を含む血液や尿サンプル測定前の処理方法として、除タンパク処理液、遠心分離法の最適化を通して、サンプル採取から測定完了までの時間は、8分以内と短時間を実現した。
  また、センサの薬物選択特異性を付加するために、ドキソルビシンの分子鋳型を作成した。作成した分子鋳型は、pH7.4条件下で、ドキソルビシンに対して特異的に吸着することを確認した。さらにこの分子鋳型は、特定条件にて吸着したドキソルビシンを分子鋳型から排出する。また、放出後は再度ドキソルビシンを吸着可能である。これにより、本分子鋳型は繰り返しの使用の可能性を示した。

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