Updated on 2025/11/30

写真a

 
YAGI Tohru
 
Organization
School of Engineering Professor
Title
Professor
External link

News & Topics

Degree

  • Doctor of Engineering ( Nagoya University )

Research Interests

  • Neural Engineering, Biomedical Engineering

  • Artificial Vision

  • Eye-gaze Interface

  • EEG

  • 医用生体工学

  • 生体情報工学

  • ロボット/システム工学

  • 視覚科学

  • 神経インタフェース

  • 人工眼

  • 人工視覚

  • 視線入力

  • 脳波

  • BCI

  • Brain Computer Interface

  • Brain Machine Interface

  • Visual Prosthesis

  • BMI

  • Biomedical Engineering

  • Biological Information Processing

  • Robotics & System Integration

  • Vision

  • Neural Interface

Research Areas

  • Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Measurement engineering  / Biomedical Engineering, Neural Engineering, Bio-MEMS, Biological Signal Processing

Education

  • Nagoya University   Graduate School of Engineering   Dept. of Electro-Mechanical Engineering

    1990 - 1996

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    Country: Japan

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  • University of Michigan   Rackham Graduate School   Bioengineering Program

    1991 - 1992

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  • Nagoya University   School of Engineering   Dept. of Mechanical Engineering

    1985 - 1990

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Research History

  • Institute of Science Tokyo   School of Engineering   Professor

    2022

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  • Tokyo Institute of Technology   School of Engineering   Associate Professor

    2016 - 2022

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  • Massachusetts Institute of Technology   School of Engineering   Fulbright Visiting Researcher

    2012 - 2013

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  • Tokyo Institute of Technology   Graduate School of Information Science and Engineering   Associate Professor

    2007 - 2016

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  • Tokyo Institute of Technology   Graduate School of Information Science and Engineering   Associate Professor

    2005 - 2007

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  • Institute of Physical and Chemical Research   Biomimetic Control Research Center   Researcher

    2004 - 2005

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  • The University of Tokyo   Research Center for Advanced Science and Technology   Visiting Researcher

    2004 - 2005

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  • NIDEK Co., Ltd.   Artiricial Vision Institute Research   Director

    2001 - 2004

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  • The Institute of Physical and Chemical Research   Bio-mimetic Control Research Center   Adjunct Research Scientist

    2000 - 2004

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  • Nagoya University   Graduate School of Engineering   Assistant Professor

    1998 - 2001

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  • Toyota National College of Technology   Dept. of Information and Computer Engineering   Adjunct Lecturer

    1998 - 2000

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  • The Institute of Physical and Chemical Research   Postdoctoral Research Scientist

    1996 - 1998

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  • Nagoya University   Graduate School of Engineering   JSPS Researcher (DC2)

    1994 - 1996

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Professional Memberships

Committee Memberships

  • The Institute of Electrical Engineering of Japan (IEEJ)   Chairman of Electronics, Information and Systems Society  

    2025   

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    Committee type:Academic society

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Papers

  • Synthetic DNA nanopores for direct molecular transmission between lipid vesicles. International journal

    Zugui Peng, Shoichiro Kanno, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    Nanoscale   2024.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    Lipid vesicles hold potential as artificial cells in bottom-up synthetic biology, and as tools in drug delivery and biosensing. Transmitting molecular signals is a key function for vesicle-based systems. One strategy to achieve this function is by releasing molecular signals from vesicles through nanopores. Nevertheless, in this strategy, an excess of molecular signals may be required to reach the targets, due to the dispersion of the signals during diffusion. The key to achieving the efficient utilization of signals is to shorten the distance between the sender vesicle and the target. Here, we present a pair of DNA nanopores that can connect and form a direct molecular pathway between vesicles. The nanopores are self-assembled from nine single DNA strands, including six 14-nucleotide single-stranded overhangs as sticky-end segments, enabling them to bind with each other. Incorporating nanopores shortens the distance between different populations of vesicles, allowing less diffusion of molecules into bulk solution. To further reduce the loss of molecules, a DNA nanocap is added to one of the nanopore's openings. The nanocap can be removed through the toehold-mediated DNA strand displacement when the nanopore meets its counterpart. Our DNA nanopores provide a novel molecular transmission tool to lipid vesicles-based systems.

    DOI: 10.1039/d4nr01344a

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  • Effects of inserting ultrashort carbon nanotubes into lipid bilayers on membrane morphology

    Shoichiro Kanno, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    Electronics and Communications in Japan   2024.6

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Abstract

    Single‐walled carbon nanotubes (CNTs) are carbon materials with unique thermal, optical, mechanical, and electrical properties, with hollow cylindrical structures of a few nanometers in diameter. CNTs cut to about 10 nm (Ultrashort CNTs, US‐CNTs) can spontaneously insert into lipid bilayers. Therefore, applications have been proposed to combine CNTs with lipid bilayers to give the membranes the properties of CNTs. However, CNTs interact with membranes to induce morphological changes in the membranes, which may hinder these applications. In this study, to investigate the effects, US‐CNTs are exposed to lipid bilayer vesicles (giant unilamellar vesicles, GUVs), which are used as a model for cell membranes, and the changes in membrane morphology with each US‐CNT concentration were evaluated by fluorescence microscopy. As a result, GUVs show morphological changes upon exposure to US‐CNTs, eventually transforming into a multiple vesicle‐linked shape. This result suggests an increase in the area and asymmetry of the GUV membrane. Based on these results, we have proposed a hypothesis regarding the mechanism of morphological changes induced in the GUV membranes by US‐CNTs exposure.

    DOI: 10.1002/ecj.12461

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  • 脂質二重膜への超短カーボンナノチューブ挿入が及ぼす膜形態への影響

    Shoichiro Kanno, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   144 ( 5 )   424 - 430   2024.5

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    Publishing type:Research paper (scientific journal)   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.144.424

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  • Ultrasound-Responsive Liposome-Encapsulated Gel Patches Drug Delivery Model

    Kano Kajie, Shoichiro Kanno, Zugui Peng, Kenta Shimba, Takashi Shibata, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   144 ( 5 )   465 - 466   2024.5

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    Publishing type:Research paper (scientific journal)   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.144.465

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  • 生体適合性と電気的特性に優れた電極の開発に向けたカーボンナノチューブの細胞接着性に関する研究

    Kittawat Wardcharoen, Shoichiro Kanno, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   144 ( 5 )   467 - 468   2024.5

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    Publishing type:Research paper (scientific journal)   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.144.467

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  • 瞳孔括約筋を模倣したバイオアクチュエータの開発

    Yuto Okayasu, Yuya Shimomura, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   144 ( 5 )   463 - 464   2024.5

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    Publishing type:Research paper (scientific journal)   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.144.463

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  • Synthetic DNA nanopores for direct molecular transmission between lipid vesicles

    Zugui Peng, Shoichiro Kanno, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    Nanoscale   2024

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    Publishing type:Research paper (scientific journal)   Publisher:Royal Society of Chemistry (RSC)  

    We designed a pair of DNA nanopores that can connect and form a direct molecular pathway between lipid vesicles.

    DOI: 10.1039/d4nr01344a

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  • A Study on Cell Culture Scaffolds using Magnetic Gel

    Yuya Shimomura, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   143 ( 7 )   714 - 715   2023.7

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    Publishing type:Research paper (scientific journal)   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.143.714

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  • A Study on DDS with High Response to Ultrasound using Metal Nanoparticle-encapsulated Liposomes

    Yukine Tagai, Kano Kajie, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Takashi Shibata, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   143 ( 7 )   712 - 713   2023.7

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    Publishing type:Research paper (scientific journal)   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.143.712

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  • Dimethyl Sulfoxide-Free Cryopreservation of Differentiated Human Neuronal Cells International journal

    Kenji Yamatoya, Yuya Nagai, Naozumi Teramoto, Woojin Kang, Kenji Miyado, Kazuya Nakata, Tohru Yagi, Yoshitaka Miyamoto

    Biopreservation and Biobanking   21 ( 6 )   631 - 634   2023.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Mary Ann Liebert Inc  

    In recent years, cells provided by cell banks and medical facilities have been used for cell therapy, regenerative therapy, and fundamental research. Cryopreservation is an effective means of maintaining stable cell quality over a long period of time. The slow freezing method is most suitable for processing many human cells isolated simultaneously from organs and tissues, but it is necessary to develop a freezing solution for this method. In this study, we report the successful development of a dimethyl sulfoxide (DMSO)-free freezing medium for differentiated neuronal cells. Neuronal differentiation results in the differentiation of undifferentiated SK-N-SH cells into neuronal cells. A basic freezing medium (BFM) was prepared using Dulbecco's modified Eagle's medium, 1 M maltose, and 1% sericin as the essential ingredients, supplemented with 5%-40% propylene glycol (PG). Each BFM supplemented with 5%-40% PG was evaluated in undifferentiated cells. After thawing, BFM supplemented with 10% and 20% PG were 83% and 88% viable, respectively. There was no significant difference between the 10% and 20% PG groups. However, a significant difference was observed when the concentration of PG in the BFM decreased by 5% (5% PG vs. 10% PG; p = 0.0026). Each DMSO-free BFM was evaluated using differentiated neuronal cells. There was no significant difference between the 10% PG BFM and stem-CB-free groups. Viability was significantly different in the 10% glycerol BFM (4.8%) and 10% PG BFM (45%) (p = 0.028). The differentiated cells with 10% PG BFM showed higher adherence to culture dishes than those with 10% glycerol BFM. These results show that BFM containing PG was effective in differentiating neuronal cells. DMSO affects the central nervous system at low concentrations. This report indicates that DMSO is unsuitable for neuronal cells with multipotent differentiation potential. Therefore, it is essential for cell banking and transplantation medicine services to select appropriate cell freezing media.

    DOI: 10.1089/bio.2022.0180

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    Other Link: https://www.liebertpub.com/doi/pdf/10.1089/bio.2022.0180

  • Control of Drug Release in Ultrasound-Responsive Liposome-Encapsulated Gel Patches.

    Kano Kajie, Zugui Peng, Kenta Shimba, Takashi Shibata 0006, Yoshitaka Miyamoto, Tohru Yagi

    MeMeA   1 - 5   2023

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    Publishing type:Research paper (international conference proceedings)  

    DOI: 10.1109/MeMeA57477.2023.10171928

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    Other Link: https://dblp.uni-trier.de/db/conf/memea/memea2023.html#KajiePSSMY23

  • Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles Reviewed

    Yoshitaka Miyamoto, Yumie Koshidaka, Katsutoshi Murase, Shoichiro Kanno, Hirofumi Noguchi, Kenji Miyado, Takeshi Ikeya, Satoshi Suzuki, Tohru Yagi, Naozumi Teramoto, Shuji Hayashi

    Materials   15 ( 21 )   7823 - 7823   2022.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Establishing a rapid in vitro evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, in vitro three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-ableTM) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions. MRI contrast agents are widely used as safe and minimally invasive diagnostic methods. We focused on anionic polysaccharide magnetic iron oxide nanoparticles (Resovist®) and synthesized the four types of nanoparticle derivatives with different properties. Cationic nanoparticles (TMADM) can be used to label target cells in a short time and have been successfully visualized in vivo. In this study, we examined the morphology of various nanoparticles. The morphology of various nanoparticles showed relatively smooth-edged spherical shapes. As 3D liver models, we prepared primary hepatocyte–endothelial cell heterospheroids. The toxicity, CYP3A, and albumin secretory capacity were evaluated in the heterospheroids labeled with various nanoparticles. As the culture period progressed, the heterospheroids labeled with anionic and cationic nanoparticles showed lower liver function than non-labeled heterospheroids. In the future, there is a need to improve the method of creation of artificial 3D liver or to design a low-invasive MRI contrast agent to label the artificial 3D liver.

    DOI: 10.3390/ma15217823

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  • Cryopreservation of undifferentiated and differentiated human neuronal cells International journal

    Kenji Yamatoya, Yuya Nagai, Naozumi Teramoto, Woojin Kang, Kenji Miyado, Kazuya Nakata, Tohru Yagi, Yoshitaka Miyamoto

    Regenerative Therapy   19   58 - 68   2022.3

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    DOI: 10.1016/j.reth.2021.12.007

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  • Development of a Battery Using a Hydrogel Network

    Kohtaro Hongo, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    2022 14TH BIOMEDICAL ENGINEERING INTERNATIONAL CONFERENCE (BMEICON 2022)   2022

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    DOI: 10.1109/BMEiCON56653.2022.10012086

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  • Transmembrane Carbon Nanotubes for Intracellular Stimulation

    Shoichiro Kanno, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    2022 14TH BIOMEDICAL ENGINEERING INTERNATIONAL CONFERENCE (BMEICON 2022)   2022

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    Language:English   Publishing type:Research paper (international conference proceedings)  

    DOI: 10.1109/BMEiCON56653.2022.10012082

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  • Development of Variable-Elasticity Cell Scaffolds Using Magnetic Gels

    Yuya Shimomura, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    2022 14TH BIOMEDICAL ENGINEERING INTERNATIONAL CONFERENCE (BMEICON 2022)   2022

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    Language:English   Publishing type:Research paper (international conference proceedings)  

    DOI: 10.1109/BMEiCON56653.2022.10012083

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  • Enhancement of the Response to Ultrasound by Encapsulating Metal Nanoparticles in Liposomes

    Yukine Tagai, Kano Kajie, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Takashi Shibata, Tohru Yagi

    2022 14TH BIOMEDICAL ENGINEERING INTERNATIONAL CONFERENCE (BMEICON 2022)   2022

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    DOI: 10.1109/BMEiCON56653.2022.10012081

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  • Development of novel ECM which has stiffness difference based on hydrogel beads

    Hiromu Miyata, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    ELECTRONICS AND COMMUNICATIONS IN JAPAN   104 ( 3 )   2021.9

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    DOI: 10.1002/ecj.12321

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  • A Study of the Effects of Plasma Surface Treatment on Lipid Bilayers Self-Spreading on a Polydimethylsiloxane Substrate under Different Treatment Times. Reviewed International journal

    Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    Langmuir : the ACS journal of surfaces and colloids   37 ( 36 )   10732 - 10740   2021.8

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    DOI: 10.1021/acs.langmuir.1c01319

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  • Effect of Magnetic Nanoparticle Internalization on Cell Density in Skeletal Muscle Tissue Reviewed

    Yuji Kirihara, Hiromu Miyata, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Kazunori Shimizu, Hiroyuki Honda, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   141 ( 7 )   795 - 801   2021.7

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    Language:English   Publisher:Institute of Electrical Engineers of Japan (IEE Japan)  

    DOI: 10.1541/ieejeiss.141.795

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  • Functional analysis of liposomes containing Single-Walled Carbon Nanotubes (SWNTs) by fluorescence microscopy Reviewed

    Shoichiro Kanno, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   141 ( 5 )   620 - 626   2021

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    DOI: 10.1541/ieejeiss.141.620

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  • Development of novel ECM which has stiffness difference based on hydrogel beads Reviewed

    Hiromu Miyata, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   141 ( 5 )   607 - 613   2021

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  • Formation of agarose-supported liposomes by polymer-assisted method toward biosensor Reviewed

    Zugui Peng, Kentaro Wada, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   141 ( 5 )   646 - 653   2021

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    DOI: 10.1541/ieejeiss.141.646

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  • Preparation of Size-controlled Giant Vesicles Under Physiological Conditions. Reviewed International journal

    Zugui Peng, Shoichiro Kanno, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference   2020   2198 - 2201   2020.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1109/EMBC44109.2020.9175877

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  • Nanopore lipid bilayer formed by self-spreading method

    Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    ELECTRONICS AND COMMUNICATIONS IN JAPAN   102 ( 12 )   47 - 54   2019.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/ecj.12225

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  • Preparation of giant lipobeads using a gel-assisted swelling method Reviewed

    Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    BMEiCON 2019 - 12th Biomedical Engineering International Conference   2019.11

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    Language:English   Publishing type:Research paper (international conference proceedings)  

    DOI: 10.1109/BMEiCON47515.2019.8990310

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  • Nanopore-spanning lipid bilayer formed by self-spreading method

    Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    BMEiCON 2018 - 11th Biomedical Engineering International Conference   139 ( 10 )   1146 - 1152   2019.1

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    DOI: 10.1109/BMEiCON.2018.8609982

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  • Effect of the amount of carbon nanotubes introduced into liposomes on membrane permeability

    Shoichiro Kanno, Zugui Peng, Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    13TH BIOMEDICAL ENGINEERING INTERNATIONAL CONFERENCE (BMEICON 2021)   2018

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    DOI: 10.1109/BMEiCON53485.2021.9745234

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  • Hydrogel-supported bilayers for studying membrane protein functions Reviewed

    Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    BMEiCON 2017 - 10th Biomedical Engineering International Conference   2017-   1 - 4   2017.12

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    DOI: 10.1109/BMEiCON.2017.8229152

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  • Enhanced Adipogenic Differentiation of Human Adipose-Derived Stem Cells in an In Vitro Microenvironment: The Preparation of Adipose-Like Microtissues Using a Three-Dimensional Culture. Reviewed International journal

    Yoshitaka Miyamoto, Masashi Ikeuchi, Hirofumi Noguchi, Tohru Yagi, Shuji Hayashi

    Cell medicine   9 ( 1-2 )   35 - 44   2017.1

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    The application of stem cells for cell therapy has been extensively studied in recent years. Among the various types of stem cells, human adipose tissue-derived stem cells (ASCs) can be obtained in large quantities with relatively few passages, and they possess a stable quality. ASCs can differentiate into a number of cell types, such as adipose cells and ectodermal cells. We therefore focused on the in vitro microenvironment required for such differentiation and attempted to induce the differentiation of human stem cells into microtissues using a microelectromechanical system. We first evaluated the adipogenic differentiation of human ASC spheroids in a three-dimensional (3D) culture. We then created the in vitro microenvironment using a 3D combinatorial TASCL device and attempted to induce the adipogenic differentiation of human ASCs. The differentiation of human ASC spheroids cultured in maintenance medium and those cultured in adipocyte differentiation medium was evaluated via Oil red O staining using lipid droplets based on the quantity of accumulated triglycerides. The differentiation was confirmed in both media, but the human ASCs in the 3D cultures contained higher amounts of triglycerides than those in the 2D cultures. In the short culture period, greater adipogenic differentiation was observed in the 3D cultures than in the 2D cultures. The 3D culture using the TASCL device with adipogenic differentiation medium promoted greater differentiation of human ASCs into adipogenic lineages than either a 2D culture or a culture using a maintenance medium. In summary, the TASCL device created a hospitable in vitro microenvironment and may therefore be a useful tool for the induction of differentiation in 3D culture. The resultant human ASC spheroids were "adipose-like microtissues" that formed spherical aggregation perfectly and are expected to be applicable in regenerative medicine as well as cell transplantation.

    DOI: 10.3727/215517916X693096

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  • Self-spreading method for forming lipid bilayer on a patterned agarose gel: Toward precise lipid bilayer patterning. Reviewed International journal

    Kenta Shimba, Kazuma Shoji, Yoshitaka Miyamoto, Tohru Yagi

    Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS   2017   1877 - 1880   2017

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    DOI: 10.1109/EMBC.2017.8037213

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    Other Link: https://dblp.uni-trier.de/conf/embc/2017

  • Development of a method for patterning hydrogel-supported bilayer

    Shimba Kenta, Shoji Kazuma, Miyamoto Yoshitaka, Yagi Tohru

    Transactions of Japanese Society for Medical and Biological Engineering   55 ( 5 )   449 - 449   2017

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    Language:Japanese   Publisher:Japanese Society for Medical and Biological Engineering  

    <p>Membrane proteins are major targets for drug development. Since membrane proteins must be inserted into lipid bilayers for functional evaluation, a number of method for lipid bilayer formation has been developed. However, there is a lack of efficient method for forming hydrogel-supported bilayer. Here, we aimed to develop a method for patterning a lipid bilayer on hydrogel with a large area. We applied self-spreading method for hydrogel-supported bilayer, which was originally developed for solid-supported bilayer. Agarose gel was patterned with a stripe manner, and then lipid bilayer composed of DPhPC and fluorescein-eggPC was formed on the gel. Bilayer formation was examined with fluorescence imaging and FRAP method. As a result, it is suggested that lipid bilayer was formed on the hydrogel pattern.</p>

    DOI: 10.11239/jsmbe.55Annual.449

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  • Mobile Lipid Bilayer on Agar-Coated Electrode Toward modeling cellular communication via gap junction Reviewed

    Kenta Shimba, Yoshitaka Miyamoto, Tohru Yagi

    2016 9TH BIOMEDICAL ENGINEERING INTERNATIONAL CONFERENCE (BMEICON)   2016

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  • Spheroid Formation and Evaluation of Hepatic Cells in a Three-Dimensional Culture Device. Reviewed International journal

    Yoshitaka Miyamoto, Masashi Ikeuchi, Hirofumi Noguchi, Tohru Yagi, Shuji Hayashi

    Cell medicine   8 ( 1-2 )   47 - 56   2015.12

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    In drug discovery, it is very important to evaluate liver cells within an organism. Compared to 2D culture methods, the development of 3D culture techniques for liver cells has been successful in maintaining long-term liver functionality with the formation of a hepatic-specific structure. The key to performing drug testing is the establishment of a stable in vitro evaluation system. In this article, we report a Tapered Stencil for Cluster Culture (TASCL) device developed to create liver spheroids in vitro. The TASCL device will be applied as a toxicity evaluation system for drug discovery. The TASCL device was created with an overall size of 10 mm × 10 mm, containing 400 microwells with a top aperture (500 µm × 500 µm) and a bottom aperture (300 µm diameter circular) per microwell. We evaluated the formation, recovery, and size of HepG2 spheroids in the TASCL device. The formation and recovery were both nearly 100%, and the size of the HepG2 spheroids increased with an increase in the initial cell seeding density. There were no significant differences in the sizes of the spheroids among the microwells. In addition, the HepG2 spheroids obtained using the TASCL device were alive and produced albumin. The morphology of the HepG2 spheroids was investigated using FE-SEM. The spheroids in the microwells exhibited perfectly spherical aggregation. In this report, by adjusting the size of the microwells of the TASCL device, uniform HepG2 spheroids were created, and the device facilitated more precise measurements of the liver function per HepG2 spheroid. Our TASCL device will be useful for application as a toxicity evaluation system for drug testing.

    DOI: 10.3727/215517915X689056

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  • Three-Dimensional In Vitro Hepatic Constructs Formed Using Combinatorial Tapered Stencil for Cluster Culture (TASCL) Device. Reviewed International journal

    Yoshitaka Miyamoto, Masashi Ikeuchi, Hirofumi Noguchi, Tohru Yagi, Shuji Hayashi

    Cell medicine   7 ( 2 )   67 - 74   2015.2

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    Language:English   Publishing type:Research paper (scientific journal)  

    Attempts to create artificial liver tissue from various cells have been reported as an alternative method for liver transplantation and pharmaceutical testing. In the construction of artificial liver tissue, the selection of the cell source is the most important factor. However, if an appropriate environment (in vitro/in vivo) cannot be provided for various cells, it is not possible to obtain artificial liver tissue with the desired function. Therefore, we focused on the in vitro environment and produced liver tissues using MEMS technology. In the present study, we report a combinatorial TASCL device to prepare 3D cell constructs in vitro. The TASCL device was fabricated with an overall size of 10 mm × 10 mm with microwells and a top aperture (400 µm × 400 µm, 600 µm × 600 µm, 800 µm × 800 µm) and bottom aperture (40 µm × 40 µm, 80 µm × 80 µm, 160 µm × 160 µm) per microwell. The TASCL device can be easily installed on various culture dishes with tweezers. Using plastic dishes as the bottom surface of the combinatorial TASCL device, 3D hepatocyte constructs of uniform sizes (about ɸ 100 μm-ɸ 200 μm) were produced by increasing the seeding cell density of primary mouse hepatocytes. The 3D hepatocyte constructs obtained using the TASCL device were alive and secreted albumin. On the other hand, partially adhered primary mouse hepatocytes exhibited a cobblestone morphology on the collagen-coated bottom of the individual microwells using the combinatorial TASCL device. By changing the bottom substrate of the TASCL device, the culture environment of the cell constructs was easily changed to a 3D environment. The combinatorial TASCL device described in this report can be used quickly and simply. This device will be useful for preparing hepatocyte constructs for application in drug screening and cell medicine.

    DOI: 10.3727/215517914X685187

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  • Permeability of tubular membrane protein Reviewed

    Atsushi Hattori, Tohru Yagi, Yoshitaka Miyamoto

    BMEiCON 2013 - 6th Biomedical Engineering International Conference   2013

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    DOI: 10.1109/BMEiCon.2013.6687700

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  • Saccade-related EEG signals by ICA algorithms Reviewed

    Arao Funase, Motoaki Mouri, Yagi Tohru, Andrzej Cichocki, Ichi Takumi

    2008 INTERNATIONAL SYMPOSIUM ON INFORMATION THEORY AND ITS APPLICATIONS, VOLS 1-3   961 - +   2008

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  • Study on Mental Stress Using Near-Infrared Spectroscopy, Electroencephalography, and Peripheral Arterial Tonometry Reviewed

    Yoshikazu Ishii, Hajime Ogata, Hidenori Takano, Hidenori Ohnishi, Toshiharu Mukai, Tohru Yagi

    2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8   2008   4992 - +   2008

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    DOI: 10.1109/IEMBS.2008.4650335

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  • A study on the primary motor cortex performing motor imagery task for the development of a brain-computer interface Reviewed

    Yoshikazu Ishii, Toshiharu Mukai, Tohru Yagi

    2007 IEEE INTERNATIONAL CONFERENCE ON SYSTEMS, MAN AND CYBERNETICS, VOLS 1-8   3393 - +   2007

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  • Research for estimating direction of saccadic eye movements by single trial processing

    Arao Funase, Tetsuro Hashimoto, Tohru Yagi, Allan K. Barros, Andrzej Cichocki, Ichi Takumi

    Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings   4723 - 4726   2007

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    DOI: 10.1109/IEMBS.2007.4353394

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  • Single trial analysis on saccade-related EEG signal

    Arao Funase, Tohru Yagi, Allan K. Barros, Andrzej Cichocki, Ichi Takumi

    Proceedings of the 3rd International IEEE EMBS Conference on Neural Engineering   371 - 374   2007

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    DOI: 10.1109/CNE.2007.369687

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  • Drifting and blinking compensation in electro-oculography (EOG) eye-gaze interface

    Tohru Yagi, Yoshiaki Kuno, Kazuo Koga, Toshiharu Mukai

    Conference Proceedings - IEEE International Conference on Systems, Man and Cybernetics   4   3222 - 3226   2006

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    Language:English   Publishing type:Research paper (international conference proceedings)   Publisher:Institute of Electrical and Electronics Engineers Inc.  

    DOI: 10.1109/ICSMC.2006.384613

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  • Single trial method for brain-computer interface

    Arao Funase, Tohru Yagi, Allan K. Barros, Andrzej Cichocki, Ichi Takumi

    Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings   5277 - 5281   2006

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    DOI: 10.1109/IEMBS.2006.259741

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  • Comparison of saccade-related EEG signal with saccade-related independent component

    Arao Funase, Tohru Yagi, Allan K. Barros, Andrzej Cichocki, Ichi Takumi

    Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings   7   7060 - 7063   2005

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    Language:English   Publishing type:Research paper (international conference proceedings)   Publisher:Institute of Electrical and Electronics Engineers Inc.  

    DOI: 10.1109/iembs.2005.1616132

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  • Biohybrid retinal implant: Research and development update in 2005

    Tohru Yagi, Masami Watanabe, Yasushi Ohnishi, Shigeru Okuma, Toshiharu Mukai

    2nd International IEEE EMBS Conference on Neural Engineering   2005   248 - 251   2005

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    Language:English   Publishing type:Research paper (international conference proceedings)  

    DOI: 10.1109/CNE.2005.1419603

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  • Fundamental research for EEG interface: EEG and auditory/visual stimulus during eye-movements

    Arao Funase, Tohru Yagi, Yoshiaki Kuno, Yoshiki Uchikawa

    Proceedings of the IEEE International Conference on Systems, Man and Cybernetics   2   1999

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Books

  • ブレイン-マシン・インタフェース最前線

    株式会社 工業調査会  2007 

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  • 光技術動向調査報告書XIX

    財団法人光産業技術振興協会  2003 

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  • マイクロマシン

    産業技術サービスセンター  2002 

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  • Intelligent Robots and Systems

    Elsevier  1995 

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  • Intelligent Robots and Systems

    Elsevier  1995 

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MISC

  • A study on regular hexagonal culture substrates for separation of cells

    佐藤颯, 下村裕哉, 菅野翔一朗, 榛葉健太, 宮本義孝, 八木透

    電気学会研究会資料(Web)   ( MBE-24-001-026 )   2024

  • Preparation of iris muscle-like tissue using mesh cell sheets

    岡安悠杜, 榛葉健太, 宮本義孝, 八木透

    電気学会研究会資料(Web)   ( MBE-24-001-026 )   2024

  • A study on the change of shrinkage by culture days about cultured muscle actuators

    豊浦達貴, 岡安悠杜, 下村裕哉, 菅野翔一朗, 榛葉健太, 宮本義孝, 八木透

    電気学会研究会資料(Web)   ( MBE-24-001-026 )   2024

  • Research on culture substrates for cell position control

    下村裕哉, 佐藤颯, 菅野翔一朗, 榛葉健太, 宮本義孝, 八木透

    電気学会研究会資料(Web)   ( MBE-24-001-026 )   2024

  • Creation of sphincter muscle tissue by controlling myofiber orientation using pillars

    岡安悠杜, 下村裕哉, 榛葉健太, 宮本義孝, 八木透

    電気学会電子・情報・システム部門大会(Web)   2023   2023

  • Development of a method for migration of adherent cells using magnetic particles

    下村裕哉, 榛葉健太, 宮本義孝, 八木透

    電気学会電子・情報・システム部門大会(Web)   2023   2023

  • コンピュータ外科の新展開 次世代のキーテクノロジー 神経インタフェースの現状と将来

    八木 透, 宮本 義孝, 菅原 路子, 中谷 裕教

    日本コンピュータ外科学会誌   17 ( 3 )   157 - 157   2015.10

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  • 創造性教育のための電気回路実習

    高橋秀智, 八木透

    設計工学   Vol. ( No. )   18,22   2007

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  • 人工眼

    八木透

    細胞   37 ( 2 )   18 - 21   2005

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  • Transretinal electrical stimulation with a suprachoroidal multichannel electrode in rabbit eyes

    Hirokazu Sakaguchi, Takashi Fujikado, Xiaoyun Fang, Hiroyuki Kanda, Makoto Osanai, Kazuaki Nakauchi, Yasushi Ikuno, Motohiro Kamei, Tohru Yagi, Shigeru Nishimura, Masahito Ohji, Tetsuya Yagi, Yasuo Tano

    Japanese Journal of Ophthalmology   48 ( 3 )   256 - 261   2004.5

  • ハイブリッド型人工網膜

    八木透

    応用物理   73 ( 8 )   1095 - 1100   2004

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  • 視覚神経刺激による視覚機能代行-人工眼(人工視覚)

    八木透

    BME   18 ( 4 )   36 - 42   2004

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    Language:Japanese   Publisher:Japanese Society for Medical and Biological Engineering  

    DOI: 10.11239/jsmbe1987.18.4_36

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    Other Link: http://search.jamas.or.jp/link/ui/2005058274

  • 人工網膜による機能再建

    八木透

    月刊眼科診療プラクティス   91   74 - 77   2003

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  • 人工眼(人工視覚)

    八木透

    現代医療の最前線(後編):人工臓器とメディカル・エンジニアリングの進歩   42 - 51   2003

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  • 人工網膜とその情報処理

    八木透

    脳型コンピュータの実現に向けて:脳を知り、脳を創る   78 - 73   2003

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  • 失明を克服するテクノロジー:人工眼

    八木透

    眼薬理   17   5 - 11   2003

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  • 人工視覚研究の現状-工学的立場から

    八木透

    脳21   6 ( 4 )   81 - 84   2003

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  • Analysis of EEG Related Saccadic Eye Movement

    Shigeru Okuma, Arao Funase, Yoshiaki Kuno, Tohru Yagi

    IEEJ Transactions on Electronics, Information and Systems   123 ( 1 )   93 - 99   2003

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  • 衝動性眼球運動(サッケード)関連脳波に対する独立成分解析

    船瀬新王, AllanK.Barros, 大熊繁, AndrejCichocki 八木透

    生体医工学   41 ( 4 )   342 - 351   2003

  • 導電性高分子のマイクロパターン作製

    伊藤雄一郎, 大西保志, 木内一壽, 八木透

    電気学会論文誌   122-C ( 9 )   1441 - 1446   2002

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  • 人工眼の開発:夢への挑戦

    八木透

    画像ラボ   13 ( 7 )   32 - 35   2002

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    Language:Japanese   Publisher:日本工業出版  

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  • 仮想的に再現された人工眼視覚のもとでの読書能力の定量的評価

    寺澤靖雄, 八木

    電気学会論文誌   122-C ( 7 )   1104 - 1109   2002

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  • Analysis on saccade-related EEG with independent component analysis

    A Funase, T Yagi, AK Barros, Y Kuno, Y Uchikawa

    INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS   14 ( 1-4 )   353 - 358   2001

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  • A study on conductive polymer electrodes for stimulating the nervous system

    Y Ito, T Yagi, Y Ohnishi, K Kiuchi, Y Uchikawa

    INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS   14 ( 1-4 )   347 - 352   2001

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  • Effect of pulse parameters on visual nervous system

    H Kanda, M Watanabe, T Fujikado, T Yagi

    INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS   14 ( 1-4 )   337 - 340   2001

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  • Simulation of visual prosthesis in virtual space

    Y Terasawa, T Fujikado, T Yagi

    INTERNATIONAL JOURNAL OF APPLIED ELECTROMAGNETICS AND MECHANICS   15 ( 1-4 )   431 - 436   2001

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  • Toward visual prosthesis: Electrical stimulation on the central nervous system

    H Kanda, T Yagi, Y Ito, S Tanaka, M Watanabe, Y Uchikawa

    NON-LINEAR ELECTROMAGNETIC SYSTEMS - ISEM '99   713 - 716   2000

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  • System for position detection and communication with image sensor

    Y Kuno, T Yagi, S Suzuki, Y Uchikawa

    NON-LINEAR ELECTROMAGNETIC SYSTEMS - ISEM '99   695 - 698   2000

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  • A study on Electro-Encephalogram (EEG) in eye movements

    A Funase, T Yagi, Y Kuno, Y Uchikawa

    NON-LINEAR ELECTROMAGNETIC SYSTEMS - ISEM '99   709 - 712   2000

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  • Distinct mechanisms for expression of Fos-like immunoreactivity and synaptic potentiation in telencephalic hyperstriatum of the quail chick

    S. Yanagihara, T. Yagi, T. Matsushima

    Brain Research   779 ( 1-2 )   240 - 253   1998.1

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  • Distinct mechanisms for expression of Fos-like immunoreactivity and synaptic potentiation in telencephalic hyperstriatum of the quail chick

    S Yanagihara, T Yagi, T Matsushima

    BRAIN RESEARCH   779 ( 1-2 )   240 - 253   1998.1

  • EOGを用いた視線入力インタフェースの開発

    久野悦章, 藤井一幸, 八木透, 内川嘉樹

    情報処理学会論文誌   39 ( 5 )   1455 - 1462   1998

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  • Hybrid retinal implant

    UCHIKAWA Yoshiki, YAGI Tohru

    Journal of the Japanese Society for Artificial Organs and Tissues   27 ( 5 )   703 - 707   1998

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    Language:Japanese   Publisher:JAPANESE SOCIETY FOR ARTIFICIAL ORGANS  

    DOI: 10.11392/jsao1972.27.5_703

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    Other Link: http://search.jamas.or.jp/link/ui/1999145710

  • Active vision inspired by mammalian fixation mechanism

    Yagi, T. Asano, N. Makita, S. Uchikawa

    Intelligent Robots and Systems   39 - 47   1995

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  • Active vision inspired by mammalian fixation mechanism

    Yagi, T. Asano, N. Makita, S. Uchikawa

    Intelligent Robots and Systems   39 - 47   1995

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  • Active Vision System Inspired by Biological Fixation Mechanism

    YAGI Tohru, ASANO Nobuhisa, MAKITA Shinji, UCHIKAWA Yoshiki

    Transactions of the Japan Society of Mechanical Engineers. Series C.   61 ( 591 )   4402 - 4409   1995

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    Language:Japanese   Publisher:The Japan Society of Mechanical Engineers  

    Focusing on the biological fixation mechanism, we propose a fixation technique, and implement it into an active vision system. In our technique, large and small camera movements are coordinated to detect an object precisely at the optical axis of the camera. Each type of movement is performed via two separate fixation methods : approximate fixation and adjustment fixation. In the former fixation, a preliminary fixation point is detected using the multi-resolution retina. After the optical axis of the camera is aligned in the direction of this point, the latter fixation method determines the precise fixation point by means of visual feedback control, which minimized the angle between the object's center and the optical axis of the camera. Experimental results show that the active vision system using our proposed technique succeded in fixating objects one after another in a scene, even if several objects are placed within it. According to these results, we have confirmed that bottom-up processing using primitive visual features is an effective technique for precise fixation.

    DOI: 10.1299/kikaic.61.4402

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  • An algorithm of eye movements in biological vision, Simulation and Design of Applied Electromagnetic Systems

    Yagi, T. Gouhara, K. Uchikawa

    Elsevier Studies in Applied Electromagnetics in Materials   5   415 - 418   1993

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  • An algorithm of eye movements in biological vision, Simulation and Design of Applied Electromagnetic Systems

    Yagi, T. Gouhara, K. Uchikawa

    Elsevier Studies in Applied Electromagnetics in Materials   5   415 - 418   1993

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Presentations

  • Biohybrid retinal implant: Research and development update in 2005

    2005 

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  • Biohybrid retinal implant: Research and development update in 2005

    2005 

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Awards

  • 計測自動制御学会SI部門奨励賞

    2005  

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    Country:Japan

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  • 計測自動制御学会システムインテグレーション部門SI2004 ベストセッション講演賞

    2004  

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  • 平成16年電気関係学会東海支部連合大会奨励賞

    2004  

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  • 平成10年度電気通信普及財団賞

    1998  

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Research Projects

  • Research and development of neural interface devices using nanotubes and artificial cell membranes

    Grant number:23K25191  2022.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

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  • Research and development of neural interface devices using nanotubes and artificial cell membranes

    Grant number:22H03937  2022.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

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  • Neural interface for biohybrid artificial limbs that realize sensory and motor functions

    Grant number:21H00323  2021.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

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    Grant amount:\11310000 ( Direct Cost: \8700000 、 Indirect Cost:\2610000 )

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  • Research and development of neural interface device composed of artificial cell membrane and membrane protein

    Grant number:18H03512  2018.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

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  • The visualization of microtissues using near-infrared fluorescence endoscope

    Grant number:16K12921  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Miyamoto Yoshitaka, CHIBA Toshio, IKEUCHI Masashi, NOGUCHI Hirofumi, SHIMBA Kenta, SUZUKI Satoshi, HAYASHI Shuji

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    Grant amount:\3510000 ( Direct Cost: \2700000 、 Indirect Cost:\810000 )

    Near-infrared fluorescence endoscope system with indocyanine green (ICG) is a powerful tool to observe the interior tissues and organs in surgery in real time. It is useful especially in a wide range of surgical fields. Since ICG has strong near-infrared fluorescence, it can be visualized while excluding the effect of autofluorescence of tissues. In this study, we successfully labeled microtissues with ICG and then visualized them in real time. The near-infrared fluorescence endoscope system was helpful to observe microtissues with different sizes at high sensitivity (about 100-10,000 cell clusters) in vitro (the surface of pig small intestine, etc). Although the noise was amplified with increasing the sensitivity, it can be reduced by adjusting the threshold level. Our system can contribute to improving the safety of transplantation in regenerative therapy and cell medicine, and its medical applications will be expanded more and more in the future.

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  • Development of cryopreservation system for cells and tissue constructs in regenerative medicine and transplantation

    Grant number:15H03039  2015.4 - 2018.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    MIYAMOTO Yoshitaka, MIYADO Kenji, YAGI Tohru, TERAMOTO Naozumi, NOGUCHI Hirofumi, IKUTA Koji, MIURA Takumi

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    Grant amount:\17030000 ( Direct Cost: \13100000 、 Indirect Cost:\3930000 )

    In this study, we developed a novel (1) DMSO-free cryopreservation solution, (2) culture device for cryopreservation, and (3) freezing system. (1) In order to safely freeze cells, it is necessary to solve the problems such as the cytotoxicity of DMSO, the antigenicity change of animal-derived materials and the possibility of contamination with pathogens. We found an optimal composition of cryopreservation solution without DMSO and serum for human cells. (2) 3D culture device TASCL was used to create a large amount of human tissue-derived stem cell constructs having a uniform size. In addition, we successfully determined a vitrified freezing condition based on the effective composition of the freezing solution. (3) In order to control cell freezing, we succeeded in developing a freezing system with a stirling engine and in optimizing freezing conditions. Consequently, a cryopreservation system of cell tissue construct for regeneration and transplantation medical care was established.

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  • Construction of a cytotoxicity and function evaluation system using combinatorial cell clusters with magnetic nanoparticles

    Grant number:25560248  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    MIYAMOTO Yoshitaka, IKEUCHI Masashi, NOGUCHI Hirofumi, YAGI Tohru, HAYASHI Shuji, SUZUKI Satoshi, IKUTA Koji

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    Grant amount:\3770000 ( Direct Cost: \2900000 、 Indirect Cost:\870000 )

    This study aims to construct an evaluation system by combinatorial cell clusters. The cell clusters with various sizes were successfully prepared efficiently on our developed micro-fabricated device in a one-cell seeding. Furthermore, commercially available MRI contrast agents and our magnetic nanoparticles for MRI imaging were assessed for toxicity and cell functions by combinatorial hepatocyte clusters formed on this device. As a result, resultant clusters were also successfully evaluated for cell viability, cell proliferation, cytotoxicity, and functions at the protein level. Furthermore, it was possible to confirm the reproducibility and efficacy of other cell types such as adipose-derived stem cells on their toxicity and functions.

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  • Development of Bio-stimulation Electrode Using Membrane Protein

    Grant number:22650103  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    YAGI Tohru

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    Grant amount:\3440000 ( Direct Cost: \2900000 、 Indirect Cost:\540000 )

    Tubular membrane protein’s ion permeation function is available for biomedical applications such as cell stimulation devices. However, when considering that those proteins stimulate the multiple cells in parallel, it is not easy to evaluate each function to the cell at the same time by electrical measurements. Therefore, we propose the use of ion sensor to evaluate the protein’s electrical properties on the basis of its fluorescence images. In this study, we introduced target proteins into an artificial lipid bilayer membrane where the ion concentration gradient exists. Then, we observe fluorescence images and record electrical properties of the membrane.

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  • Construction of nerve cell body on a 3-dimensional culture device

    Grant number:22650127  2010 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    MIYAMOTO Yoshitaka, IKEUCHI Masashi, KAJI Noritada, YAGI Tohru, HAYASHI Shuji

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    Grant amount:\3320000 ( Direct Cost: \2900000 、 Indirect Cost:\420000 )

    This study aims to develop a device for the construction of three dimensional cell assemblies of nerve-like cells. The device for cell patterning has enabled to generate cell assemblies with a controlled size in large numbers and to simultaneously evaluate their functions under various culture conditions. The size of the tissues was controlled for primary cells, tissue-derived stem cells, and induced plulipotent stem(iPS) cells. The cell assemblies on the device had their drug response, and protein level analysis revealed their some functions. The 2D culture of nerve-like cells also showed that a neural-like network was generated on the device and cyclic response to electric nerve stimulation was changed.

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  • Development of an Artificial Synapse using an Integrated Electrochemical Micropump

    Grant number:18300154  2006 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    YOSHIMI Yasuo, KANAMORI Toshiyuki, YAGI Tohru

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    Grant amount:\13300000 ( Direct Cost: \11800000 、 Indirect Cost:\1500000 )

    The final purpose of this project is a development of integrated micropumps working as an interface between electric circuits and neurons or an artificial synapse. We developed a chip of micropump with microvalve using electrodecomposition of water as a driving force. The chip can control the jetting with punctuality to the second. The pump could induce excitatory postsynaptic potential of Aplysia neuron by neurotransmitter administration. We developed also voltage imaging for central nerve system for evaluation of the ability of the interface. It has been difficult to detect the action potential of Aplysia neuron by voltage imaging. We succeeded in the detection of the action potential by prolonging by tetraethylammonium chloride as a potassium channel blocker. The technologies developed in the project will help the development of neuronal interface by neurotransmitter administration.

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  • Visual Prosthesis -Study of hybrid retinal implant-

    Grant number:12358016  2000 - 2003

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    MIYAKE Yuzo, KONDO Mineko, WATANABE Masami, ISHIGURO Akio, KONDO Nagako

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    Grant amount:\47730000 ( Direct Cost: \39600000 、 Indirect Cost:\8130000 )

    (1) Simulation of visual prosthesis in virtual system : It is essential to determine the specifications which meet the minimal needs in daily lives of patients. For this purpose, a prosthetic vision simulator was developed, which enables to experience prosthetic vision in the visual space. Experimental results suggested that the electric current intensity in simulation has small effects to the reading ability. (2) Imaging signal analysis : To get proper electrical stimulation to the retina, the special hardware was developed with a compact curcuit. We proved this device is essential for retinal prosthesis. (3) Evaluation of electrical stimulus to visual neuron : To investigate the most suitable stimulus condition of the electrical pulse to the retina, normal and retinal degenerated rats were used. We found that short wave stimuli are more effective than pulse waves. Using cats, the visual evoked response from the visual cortex were evaluated changing the pulse width, pulse intensity and distance of electrodes by putting the stimulus electrode array on the lateral geniculate. We found that the pulse intensity influences the response more than pulse width. (4) The modification of stimulus electrode for human retina : Several modifications were made for the retinal exoplant in human. The optical coherence tomography was found to be a good monitor to check the depth and location of the exoplant. (5) Survival and axonal regeneration of retinal ganglion cells in adult cats : We introduced several methods to rescure the axotomized cat retinal ganglion cells from apotosis and regulate their axons ; transplantation of the peripheral nerve, intraocular injections of neurotrophic factors, or an antiapotopic drug.

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  • 導電性高分子を用いたバイオ・シリコン融合素子に関する研究

    Grant number:12838006  2000 - 2002

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    内川 嘉樹, 大西 保志, 八木 透

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    Grant amount:\2300000 ( Direct Cost: \2300000 )

    半導体素子上に培養した神経細胞回路において問題となるのは、神経細胞と素子との親和性である。そこで本研究では、神経細胞と電極をつなぐインタフェースとして導電性高分子を使用し、生体との親和性を高めつつ、素子から神経細胞への信号伝達効率を下げないような、バイオ/シリコン融合素子の開発を目指す。導電性高分子は生体との親和性も高く、かつ導電性を持つことが特徴であるが、その加工方法には工夫を要する。導電性高分子の多くは、炭素-炭素共役二重結合がつながった分子構造をしているため、不融不溶であり、重合後に通常の高分子の熱加工方法などは適用できないと言う欠点を持っている。そこで本年度は、ポリビニルアルコールをマトリックスとする方法により、ポリピロールのマイクロパターン作製と、培養細胞を用いた生体適合性の評価を行なった。パターン作製には、酸化重合剤の光反応性を利用したフォトリソグラフィを用いた。その結果、マスクパターンの露光時間やピロールの重合時間を最適に設定すれば、最小線幅3μmのポリピロールパターンを作製できることが判明した。またポリピロール上に細胞を培養した結果、培養細胞は突起を伸展して成長し、4週間にわたって生存した。これらの結果より、電極アレイに適用可能な微小サイズまでポリピロールパターンを微小化できることが示された。またポリピロールは高い生体適合性を持つことが示された。

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  • 半導体素子上に培養した神経細胞の回路形成に関する研究

    Grant number:12019229  1999 - 2000

    日本学術振興会  科学研究費助成事業  特定領域研究(A)

    八木 透, 時田 義人, 児玉 哲司

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    Grant amount:\1900000 ( Direct Cost: \1900000 )

    半導体素子上に神経細胞を培養し、その軸索伸長を人工的に制御して神経回路を形成させる技術について研究を行う。そして将来は「神経インタフェース」や「バイオチッブ」の開発へと発展させる計画である。これまでITO(indium tin oxide)や白金など、生体適合性が比較的高いといわれる金属材料を用いて作製した微小電極アレイ上に神経細胞を培養し、その軸索誘導を試みてきた。しかし電極アレイ上に細胞を直接培養しようとすると、細胞が培養途中で死滅してしまうため、ポリリジンや細胞外マトリクス分子で電極アレイ表面をコーティングする必要があった。しかしコーティングはインピーダンスを増加させるため、細胞への電気刺激ならびに細胞からの電気記録には好ましくない。したがって生体組織との適合性および導電性の低下を同時に解決する必要がある。そこで我々は、導電性高分子の一つであるポリピロールを材料とすることにより、高い生体適合性と導電性を持つ電極アレイが作製できると考えた。
    そこで本年度は、ポリピロールのマイクロパターン作製と、培養細胞を用いた生体適合性の評価を行なった。パターン作製には、酸化重合剤の光反応性を利用したフォトリソグラフィを用いた。その結果、マスクパターンの露光時間やピロールの重合時間を最適に設定すれば、最小線幅3μmのポリピロールパターンを作製できることが判明した。またポリピロール上に細胞を培養した結果、培養細胞は突起を伸展して成長し4週間にわたって生存した。これらの結果より、電極アレイに適用可能な微小サイズまでポリピロールパターンを微小化できることが示された。またポリピロールは高い生体適合性を持つことが示された。

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  • 半導体素子上に培養した神経細胞の回路形成に関する研究

    Grant number:11132229  1999

    日本学術振興会  科学研究費助成事業  特定領域研究(A)

    八木 透, 時田 義人, 児玉 哲司

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    Grant amount:\2000000 ( Direct Cost: \2000000 )

    神経回路を人工的に作る方法として、1)軸索伸長に関係する各種タンパク分子の濃度勾配を人工的に作る、2)生体組織に親和性の高い物質で基盤上にパターンを作る、3)電界をつくる、4)軸索が伸長しやすいような溝(ガイドウェイ)を培養ディッシュ底につくる、などが考えられる。これらのうち今回は3)に着目して、電界と軸索伸長について調べる。
    まず、電極周辺にどのような電界が形成されるかについてコンピュータシミュレーションを行った。シミュレーションでは、正極と負極に1.5Vの電圧を加え、ポアソン方程式と有限要素法を用いて電界を計算している。なお電極周囲はリンガー液で満たされているものとした。図1は、電極周辺に形成される電界分布を色の濃淡で示したグラフで、左から正負電極間距離が100、200、300μmの場合を示している。同図の上段は電極を断面方向から眺めた場合の電界分布、下段は上方から眺めた場合の電界分布のうち長軸方向の半分の分布を表示している。容易に推測されるように、電極近傍で高い電界強度が観測されている。また正負極間の距離を変更すると電界分布が大きく変化することがわかる。また基盤内部に電界が形成されていることがわかるが、これはクロストークの原因になる可能性があり、さらには電極と神経組織との信号伝達効率を低下させる可能性があると考えられる。
    次に、市販の多点電極ディッシュ(ガラス基盤上にフォトリソグラフィでITOを用いてパターン化し、ポリイミドでコーティングをしたもので、電極部分が金でめっきされている)の上に、成ラットの後根神経節から採取した神経細胞を培養し、任意の電極を正極と負極に選び、1.5Vの直流電圧を加えて形成した静電界において、神経細胞の軸索伸長を観察した。なお基盤上への神経細胞の接着を良くする目的で接着分子を塗布した(ポリリジン、コンカナバリン、コラーゲンの3種について実施)。負極に向けて神経突起の伸展が観察されるのではないかと予想したが、今回の実験条件ではそのような傾向は見られず、またコントロールとの比較においても特定方向への突起伸展は観察できなかった。今後は、電界条件を変更して突起伸長との関係を検討する。

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  • 神経細胞を用いた生体信号計測システム「神経プローブ」に関する研究

    Grant number:11750367  1998 - 2000

    日本学術振興会  科学研究費助成事業  奨励研究(A)

    八木 透

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    Grant amount:\2200000 ( Direct Cost: \2200000 )

    半導体素子上に神経細胞を培養し、その軸索伸長を人工的に制御して神経回路を形成させる技術について研究を行う。これまでITO(indium tin oxide)や白金など、生体適合性が比較的高いといわれる金属材料を用いて作製した微小電極アレイ上に神経細胞を培養し、その軸索誘導を試みてきた。しかし電極アレイ上に細胞を直接培養しようとすると、細胞が培養途中で死滅してしまうため、ポリリジンや細胞外マトリクス分子で電極アレイ表面をコーティングする必要があった。しかしコーティングはインピーダンスを増加させるため、細胞への電気刺激ならびに細胞からの電気記録には好ましくない。したがって生体組織との適合性および導電性の低下を同時に解決する必要がある。そこで、導電性高分子の一つであるポリピロールを材料とすることにより、高い生体適合性と導電性を持つ電極アレイが作製できると考え、ポリピロールのマイクロパターン作製と、培養細胞を用いた生体適合性の評価を行なった。パターン作製には、酸化重合剤の光反応性を利用したフォトリソグラフィを用いた。その結果、マスクパターンの露光時間やピロールの重合時間を最適に設定すれば、最小線幅3μmのポリピロールパターンを作製できることが判明した。またポリピロール上に細胞を培養した結果、培養細胞は突起を伸展して成長し、4週間にわたって生存した。

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  • 培養細胞と半導体素子を用いたハイブリット型人工網膜に関する研究

    Grant number:10145105  1998

    日本学術振興会  科学研究費助成事業  特定領域研究(A)

    内川 嘉樹, 八木 透, 時田 義人, 児玉 哲司, 川瀬 和秀, 渡部 眞三

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    Grant amount:\2000000 ( Direct Cost: \2000000 )

    本研究では、培養神経細胞と光電素子を中心としたMEMS(Micro-Electro-MechanicalSystem)を組み合わせ、光覚回復を目的とした人工眼「ハイブリッド型人工網膜」の研究開発を行なっている。外部装置から光通信で送られたデータに基づき、埋め込んだ培養神経細胞を電気的に刺激する。なお末梢神経を用いて神経細胞と中枢の間を架橋することにより、その軸索を中枢へ導き、信号を伝達させようと考えている。従って提案する人工眼では、電極から培養神経細胞へ、さらに培養神経細胞から視覚中枢への伝達の安定的な再構成が、本質的な課題である。本年度は、「神経インターフェースの生体適合性と擬似神経パルスの評価」と、「外部装置から神経インターフェースへのデータ転送」について研究を行なった。
    1. 神経インターフェースの生体適合性と擬似神経パルスの評価
    動物の脳への電気刺激により、視覚野で生じる視覚誘発電位を測定した。まずは単一パルスに対する応答を記録した。パルス幅を数百μ秒から数ミリ秒まで、パルスの大きさを数μアンペアから数百μアンペアまで変化させ、電気刺激を行なったところ、パルス幅の変化よりもパルスの大きさの変化に視覚野の応答が影響されることが判明した。
    2. 外部装置から神経インターフェースへのデータ転送
    提案する人工網膜では、体外で取得した画像データ(アナログ信号)をデジタル信号へ符号化した後、光通信方式で神経インターフェースへ伝送し、神経インターフェース内の回路で擬似神経パルスを生成する必要がある。そこで赤外線LED、フォトダイオード、A/Dコンバータ、D/Aコンバータを用いて電子回路を作製し、通信の実験を行なった。その結果、比較的単純な回路でも十分にデータ転送が行なえることが判明した。

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  • A Study on Implantable Retinal Implant using Cell Culture Technique

    Grant number:08558097  1996 - 1998

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (A)

    UCHIKAWA Yoshiki, WATANABE Masami, YAGI Tohru, KODAMA Tetsuji, KAWASE Kazuhide

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    Grant amount:\16600000 ( Direct Cost: \16600000 )

    A hybrid retinal implant is a visual prosthesis to reconstruct visual sensation in the blind. It will consist of an outer apparatus and an implanted MBMS (micro-electro mechanical systems). In order to connect the MEMS with the CNS (central nervous systems) , several neurons will be cultured on the top of the MEMS.Then, their axons will be guided with the peripheral nerve fiber. After the axons reach towards the CNS, they will make the proper synaptic connection with the CNS neurons. Therefore, the adequate electrical stimulation will lead the neural cells to produce the action potential so that functional connection will be realized.
    The visual prosthesis "Hybrid Retinal Implant requires to facilitate a micro-electrode array for extracellular stimulation of nervous systems. This time, using micro-machine technology, we have fabricated a prototype of the array. In this array, aluminum cable leads are sandwiched with two dielectric layers ; silicon dioxyside and silicon nitride. First, a 400 mum thickness silicon wafer was oxidized to a thickness of 1 mum. Conductors of aluminum were next deposited to a thickness of 0.3 mum and patterned. Then, the upper dielectric layer (i.e. silicon nitride) was deposited. Using a reactive ion etching process, silicon nitride layer was partially exposed to make electrode sites. This array consists of nine channel bipolar electrodes. Two adjacent electrodes are facing each other to make nine anode/cathode pairs in a 3x3 lattice. Each electrode has 20x20 mum square shape. The distance of each pair is up to 320 mum ; therefore, the cross-talk between each pair will be reduced. Our previous computational analysis have revealed that this specification of the micro-electrode array leads to the efficient electrical stimulation to neurons. In order to evaluate its real performance, in-vivo/in-vitro extracellular stimulation experiments will be performed in our next study.
    For more information on this research, you may contact "http : //www. cmplx. cse. nagoya-u. ac. jp/research/retina/".

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