Tomokazu Matsue

Tohoku University, Miyagi, Japan

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Publications (360)1224.94 Total impact

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    ABSTRACT: We report on the effect of molecular structure and substrate material on amorphous carbon nitride (a-CN:H) electrode properties including film adhesion to the substrate and electrochemical properties. Films were prepared by neutral beam enhanced chemical vapor deposition on different substrate materials (p-type Si, Cu, Ti, and Pt) below room temperature. When depositing on Si, doping nitrogen into carbon improved the electrochemical properties despite weak adhesion to the substrate. Nitrogen in a-CN:H formed two different bonding configurations: incorporation into aromatic carbon rings and hydrogen nitride by infrared (IR) spectroscopy. Therefore, delocalization of π bonds by incorporation of nitrogen affected the electrochemical improvement of the a-CN:H electrode. For samples deposited on a different metal substrate, the adhesion to substrate increased as a function of decreasing oxygen concentration on the metal substrate surface; the Pt substrate performed well with no delamination in our evaluation. The electrochemical properties were improved only in the case of deposition on Pt. Moreover, Pt surface modification by hydrogen beam was also effective; consequently, the electrochemical property of the a-CN:H electrode was superior to the graphite electrode with high temperature annealing. The observed increases in IR spectra of aromatic clusters were in line with the electrochemical improvements of a-CN:H.
    Carbon 11/2015; 93. DOI:10.1016/j.carbon.2015.05.074 · 6.20 Impact Factor
  • Yuanshu Zhou · Kosuke Ino · Hitoshi Shiku · Tomokazu Matsue ·
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    ABSTRACT: Cellular senescence is a physiological phenomenon by which normal cells irreversibly lose their proliferative potential. Understanding the mechanisms of senescence may be helpful to elucidate the causes of ageing and for the development of anti-tumor drugs. As an indicator of senescent cells, the senescence-associated β-galactosidase (SA-β-Gal) activity at pH 6.0 has been used widely for fundamental senescence research. However, the conventional SA-β-Gal assay is not optimal for evaluating complex three-dimensional multicellular samples. We established a highly sensitive method for the direct quantification of the SA-β-Gal activity of individual multicellular spheroids within 6 min, based on scanning electrochemical microscopy (SECM). Using SECM, we successfully detected the differences in SA-β-Gal activity between MCF-7 spheroids undergoing all-trans retinoic acid (ATRA)-induced senescence and control spheroids. The SECM-based method demonstrated in this study may be widely applicable to characterize senescence processes involved in physiology and pathology.
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    ABSTRACT: This paper describes potentiometric bioimaging for enzyme activity using a large-scale integration (LSI)-based electrochemical device with 400 sensors. Potentiometric detection is useful for bioimaging because redox species are not consumed or produced during the detection process; therefore, there is no effect on cell activity and the detectable signal is sustained. In this study, the potentiometer mode of the LSI-based device was applied for the detection of glucose oxidase (GOx) and alkaline phosphatase (ALP) activity. The enzyme activities were quantitatively detected within the concentration ranges of 25-250μg/mL and 0.10-5.0ng/mL. In addition, GOx activity in hydrogels and the ALP activity of embryoid bodies (EBs) from embryonic stem (ES) cells were successfully imaged based on detection of the open circuit potentials of individual sensors in real time. To the best of our knowledge, this is the first report of potentiometric imaging using LSI-based electrochemical arrays to detect enzyme activity in ES cells. The LSI-based device is thus demonstrated to be a promising tool for bioimaging of enzyme activity.
    Biosensors & Bioelectronics 10/2015; 77:709-714. DOI:10.1016/j.bios.2015.10.021 · 6.41 Impact Factor
  • Yusuke Kanno · Kosuke Ino · Hitoshi Shiku · Tomokazu Matsue ·
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    ABSTRACT: An electrochemical device, which consists of electrode arrays, nanocavities, and microwells, was developed for multi-electrochemical detection with high sensitivity. A local redox cycling-based electrochemical (LRC-EC) system was used for multi-electrochemical detection and signal amplification. The LRC-EC system consists of n(2) sensors with only 2n bonding pads for external connection. The nanocavities fabricated in the sensor microwells enable significant improvement of the signal amplification compared with the previous devices we have developed. The present device was successfully applied for evaluation of embryoid bodies (EBs) from embryonic stem (ES) cells via electrochemical measurements of alkaline phosphatase (ALP) activity in the EBs. In addition, the EBs were successfully trapped in the sensor microwells of the device using dielectrophoresis (DEP) manipulation, which led to high-throughput cell analysis. This device is considered to be useful for multi-electrochemical detection and imaging for bioassays including cell analysis.
    Lab on a Chip 10/2015; DOI:10.1039/C5LC01016K · 6.12 Impact Factor
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    Kosuke INO · Hitoshi SHIKU · Tomokazu MATSUE ·
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    ABSTRACT: Electrochemical imaging has been dramatically developed. Electrochemical imaging can provide images of surface chemical kinetics, and its technique has been used for several applications, such as bioanalysis. Although several electrode array devices have been proposed for electrochemical imaging, it is difficult to incorporate many electrochemical sensors into a simple electrode array device due to the lack of spaces for electrodes. To solve this problem, we developed a novel electrochemical imaging system. In this system, redox cycling is based so as to incorporate many sensors in a chip device. In this review, our strategy of the detection system and device construction are described. Finally, electrochemical bioimaging using the device is described.
    Bunseki kagaku 10/2015; 64(9):669-678. DOI:10.2116/bunsekikagaku.64.669 · 0.27 Impact Factor
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    ABSTRACT: Hydrogels with tunable electrical and mechanical properties have a wide range of biological applications in tissue engineering, biosensing, and biorobotics. In this work, palladium-based metallic glass sub-micron wires (PdMGSMWs) were employed to enhance the conductivity and mechanical strength of gelatin methacryloyl (GelMA) gels. The values of electrical resistivity and stiffness of hybrid GelMA-PdMGSMW hydrogels were varied by the concentration of the sub-micron wires in the gels. Compared with pristine GelMA gels, hybrid GelMA-PdMGSMW gels were more efficient in regulating adhesion and spreading of C2C12 myoblasts. Formation, contractility, and metabolic activity of C2C12 myotubes in GelMA hydrogels also increased upon inclusion of the PdMGSMWs and applying electrical stimulation. The latter phenomenon is likely because of the electrical conductivity of hybrid GelMA gels.
    09/2015; DOI:10.1039/c5bm00215j
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    ABSTRACT: In nanotechnological devices, mass transport can be initiated by pressure driven flow, diffusion or by employing molecular motors. As the scale decreases, molecular motors can be helpful as they are not limited by increased viscous resistance. Moreover, molecular motors can move against diffusion gradients and are naturally fitted for nanoscale transportation. Among motor proteins, kinesin has particular potential for lab-on-a-chip applications. It can be used for sorting, concentrating or as a mechanical sensor. When bound to a surface, kinesin motors propel microtubules in random directions, depending on their landing orientation. In order to circumvent this complication, the microtubule motion should be confined or guided. To this end, dielectrophoretically aligned multi-walled-carbon nanotubes (MWCNT) can be employed as nanotracks. In order to control more precisely the spatial repartition of the MWCNTs, a screening method has been implemented and tested. Polygonal patterns have been fabricated with the aim of studying the guiding and the microtubule displacement between MWCNT segments. Microtubules are observed to transfer between MWCNT segments, a prerequisite for the guiding of microtubules in MWCNT circuit-based biodevices. The effect of the MWCNT organization (crenellated or hexagonal) on the MT travel distance has been investigated as well.
    Biomedical Microdevices 08/2015; 17(4):9978. DOI:10.1007/s10544-015-9978-1 · 2.88 Impact Factor
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    ABSTRACT: In the present study, we monitored the alkaline phosphatase (ALP) activity of embryoid bodies (EBs) of mouse embryonic stem (ES) cells using a large-scale integration (LSI)-based amperometric device with 400 sensors and a pitch of 250 μm. In addition, a simulation analysis was performed to reveal the positional relationship between the EBs and the sensor electrodes toward more precise measurements. The study shows that simulation analysis can be applied for precise electrochemical imaging of three-dimensionally cultured cells by normalization of the current signals.
    Analytical Sciences 07/2015; 31(7):715-9. DOI:10.2116/analsci.31.715 · 1.39 Impact Factor
  • Yuanshu Zhou · Ikuma Fujisawa · Kosuke Ino · Tomokazu Matsue · Hitoshi Shiku ·
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    ABSTRACT: Flk-1 (VEGF receptor 2) is a well-defined mesodermal progenitor marker and the Flk-1-positive (Flk-1(+)) cells derived from embryonic stem cells (ESCs) have been known to generate hemangioblasts and cardiovascular progenitor cells, which are formed in the early and late stages of differentiation, respectively. In this study, we separated Flk-1(+) and Flk-1(-) cells from spontaneously differentiating embryoid bodies (EBs) of mouse ESCs. We found cell aggregates derived from late stage Flk-1(+) cells had a relatively small size and low oxygen consumption rate (OCR) compared with those derived from Flk-1(-) cells. Furthermore, using single-cell comprehensive gene expression analysis, we found that both Flk-1(+) and Flk-1(-) cells could be categorized into subgroups with either low or high glucose metabolic activity. We observed that metabolic suppression occurs in cells expressing an intermediate level of both Nanog and Pou5f1. Taken together, our data suggested the temporary metabolic suppression is an intrinsic feature of mesodermal differentiation.
    Molecular BioSystems 07/2015; 11(9). DOI:10.1039/C5MB00340G · 3.21 Impact Factor
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    ABSTRACT: In the present study, we used a large-scale integration (LSI)-based amperometric sensor array system, designated Bio-LSI, to image dopamine release from three-dimensional (3D)-cultured PC12 cells (PC12 spheroids). The Bio-LSI device consists of 400 sensor electrodes with a pitch of 250 um for rapid electrochemical imaging of large areas. PC12 spheroids were stimulated with K+ to release dopamine. Post-stimulation dopamine release from the PC12 spheroids was electrochemically imaged using the Bio-LSI device. The Bio-LSI clearly showed the effects of the dopaminergic drugs L-3,4-dihydroxyphenylalanine (L-DOPA) and reserpine on K+-stimulated dopamine release from PC12 spheroids. Our results demonstrate that dopamine release from PC12 spheroids can be monitored using the device, suggesting that the Bio-LSI is a promising tool for use in evaluating 3D-cultured dopaminergic cells and the effects of dopaminergic drugs. To the best of our knowledge, this report is the first to describe electrochemical imaging of dopamine release by PC12 spheroids using LSI-based amperometric sensors.
    Analytical Chemistry 05/2015; 87(12). DOI:10.1021/acs.analchem.5b01307 · 5.64 Impact Factor
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    ABSTRACT: We fabricated a platinum-based double barrel probe for scanning electrochemical microscopy-scanning ion conductance microscopy (SECM-SICM) by electrodepositing platinum onto the carbon nanoelectrode of the double barrel probe. The deposition conditions were optimized to attain highly-sensitive electrochemical measurements and imaging. Simultaneous SECM-SICM imaging of electrochemical features and noncontact topography by using the optimized probe afforded high-resolution images of epidermal growth factor receptors (EGFR) on the membrane surface of A431 cells.
    Analytical Chemistry 02/2015; DOI:10.1021/acs.analchem.5b00027 · 5.64 Impact Factor
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    ABSTRACT: Scanning ion conductance microscopy (SICM) was applied to evaluate an unlabeled secretory protein in living cells. The target protein, von Willebrand factor (vWF), was released from human endothelial cells by adding phorbol-12-myristate-13-acetate (PMA). We confirmed that SICM could be used to clearly visualize the complex network of vWF and to detect strings with widths as low as 60 nm without any artifact. By acquiring the sequential SICM images of living cells, the protrusion and strings formation were observed. We also detected the opening and closing motions of a small pore (∼500 nm), which is difficult to visualize with fluorescence methods. The results clearly demonstrate that SICM is a powerful tool to examine the changes in living cells during exocytosis.
    Analytical Chemistry 02/2015; 87(5). DOI:10.1021/ac5046388 · 5.64 Impact Factor
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    ABSTRACT: We proposed a facile, low cost, and green approach to produce stable aqueous graphene dispersions from graphite through sonication in aqueous bovine serum albumin (BSA) solution for biomedical applications. The production of high quality graphene was confirmed using microscopy images, Raman spectroscopy, UV-vis spectroscopy, and XPS. In addition, ab initio calculations revealed molecular interactions between graphene and BSA. The processability of aqueous graphene dispersions was demonstrated by fabricating conductive and mechanically robust hydrogel-graphene materials.
    Nanoscale 01/2015; 7(15):-. DOI:10.1039/C4NR07569B · 7.39 Impact Factor
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    ABSTRACT: Feedback mode-based electrochemical imaging of conductivity and topography for large substrate surfaces is presented using a large-scale integration (LSI)-based amperometric chip device with 400 sensors at a pitch of 250 μm. The LSI-based chip device has enabled rapid electrochemical imaging of large substrate surfaces, compared to scanning electrochemical microscope (SECM). Substrates modified with conductive and insulating materials were placed onto the device to acquire electrochemical signals from the substrate surface using positive and negative feedback signals. The conductivity and topography of the substrate were successfully imaged, indicating that the feedback mode-based electrochemical imaging with such a device is useful to characterize large-area substrate surfaces.
    Journal of Electroanalytical Chemistry 01/2015; 741. DOI:10.1016/j.jelechem.2015.01.020 · 2.87 Impact Factor
  • Hiroki IDA · Yasufumi TAKAHASHI · Hitoshi SHIKU · Tomokazu MATSUE ·
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    ABSTRACT: Live cell imaging is important to understand the cell function such as membrane dynamics. Scanning probe microscopy (SPM) is used for evaluation of cell surface topography with nano-scale, but in most cases the measurement induced cell damage when probe contact with the cell surface. Scanning Ion Conductance Microscopy (SICM) uses ion current as a feedback signal for nanopipette probe-sample distance control. SICM allows non-contact live cell imaging and high-resolution characterization of dynamic changes of cell surface. Furthermore, SICM can combine with other analytical tool as distance control technique.
    Hyomen Kagaku 01/2015; 36(6):313-318. DOI:10.1380/jsssj.36.313
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    ABSTRACT: Abstract Gradient biomaterials have been developed and employed as an important tool in tissue engineering and biology research since the discovery that tissues and organs are non-homogeneous, exhibiting natural functional gradients in their structure or composition. Gradient biomaterials consist of relatively gradual continuous transitions in either compositional or mechanical properties. They have been used to study cellular responses such as cell adhesion, migration, proliferation, and differentiation, and may also be useful tools in drug discovery and development. Gradients made of hydrogels and nanofibers are widely used scaffolds in tissue engineering, which have aroused great interest owing to their tunable properties and analogy to the microenvironment of native tissues. In this chapter, we classify gradient biomaterials into two main cohorts, physical and chemical/biological gradients, and describe their features and applications, particularly as tooth or bone tissue scaffolds.
    01/2015: pages 175-186; Academic Press., ISBN: 9780123971579
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    ABSTRACT: We have developed a large-scale integrated (LSI) complementary metal-oxide semiconductor (CMOS)- based amperometric sensor array system called “Bio-LSI” as a platform for electrochemical bio-imaging and multi-point biosensing with 400 measurement points. In this study, we newly developed a Bio-LSI chip with a light-shield structure and a mode-selectable function with the aim of extending the application range of Bio-LSI. The light shield created by the top metal layer of the LSI chip significantly reduces the noise generated by the photocurrent, whose value is less than 1% of the previous Bio-LSI without the light shield. The mode-selectable function enables the individual operation of 400 electrodes in off, electrometer, V1, and V2 mode. The off-mode cuts the electrode from the electric circuit. The electrometer-mode reads out the electrode potential. The V1-mode and the V2-mode set the selected sensor electrode at two different independent voltages and read out the current. We demonstrated the usefulness of the Q4 mode-selectable function. First, we displayed a dot picture based on the redox reactions of 2.0 mM ferrocenemethanol at 400 electrodes by applying two different independent voltages using the V1 and V2 modes. Second, we carried out simultaneous O2 and H2O2 detection using the V1 and V2 modes. Third, we used the off and V1 modes for the modification of the osmium-polyvinylpyridine gel polymer containing horseradish peroxidase (Os-HRP) at the selected electrodes, which act as sensors for H2O2. These results confirm that the advanced version of Bio-LSI is a promising tool that can be applied to a wide range of analytical fields.
    Lab on a Chip 11/2014; 15(3). · 6.12 Impact Factor
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    ABSTRACT: Intercalation and deintercalation of lithium ions at electrode surfaces are central to the operation of lithium-ion batteries. Yet, on the most important composite cathode surfaces, this is a rather complex process involving spatially heterogeneous reactions that have proved difficult to resolve with existing techniques. Here we report a scanning electrochemical cell microscope based approach to define a mobile electrochemical cell that is used to quantitatively visualize electrochemical phenomena at the battery cathode material LiFePO4, with resolution of ~100 nm. The technique measures electrode topography and different electrochemical properties simultaneously, and the information can be combined with complementary microscopic techniques to reveal new perspectives on structure and activity. These electrodes exhibit highly spatially heterogeneous electrochemistry at the nanoscale, both within secondary particles and at individual primary nanoparticles, which is highly dependent on the local structure and composition.
    Nature Communications 11/2014; 5:5450. DOI:10.1038/ncomms6450 · 11.47 Impact Factor
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    ABSTRACT: Dielectrophoresis (DEP) approach was employed to achieve highly aligned multi-walled carbon nanotubes (MWCNTs) within the gelatin methacrylate (GelMA) hydrogels in a facile, rapid, inexpensive, and reproducible manner. This approach enabled us to make different CNTs alignments (e.g., vertical or horizontal alignments) within the GelMA hydrogel using different electrode designs or configurations. Anisotropically aligned GelMA-CNTs hydrogels showed considerably higher conductivity compared to randomly distributed CNTs dispersed in the GelMA hydrogel and the pristine and non-conductive GelMA hydrogel. Adding 0.3 mg/mL CNTs to the GelMA hydrogel led to a slight increase in the mechanical properties of the GelMA and made it to behave as a viscoelastic material. Therefore, it can be used as a suitable scaffold for soft tissues, such as skeletal muscle tissue. 3D microarrays of skeletal muscle myofibers were then fabricated based on the GelMA and GelMA-CNTs hydrogels and they were characterized in terms of gene expressions related to the muscle cell differentiation and contraction. Owing to high electrical conductivity of aligned GelMA-CNTs hydrogels, the engineered muscle tissues cultivated on these materials demonstrated superior maturation and functionality particularly after applying the electrical stimulation (voltage 8 V, frequency 1 Hz, and duration 10 ms for 2 days) compared to the corresponding tissues obtained on the pristine GelMA and randomly distributed CNTs within the GelMA hydrogel.
    MRS Online Proceeding Library 11/2014; 1621. DOI:10.1557/opl.2014.70
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    ABSTRACT: Engineered muscle tissues demonstrate properties far from native muscle tissue. Therefore, fabrication of muscle tissues with enhanced functionalities is required to enable their use in various applications. To improve the formation of mature muscle tissues with higher functionalities, we co-cultured C2C12 myoblasts and PC12 neural cells. While alignment of the myoblasts was obtained by culturing the cells in micropatterned methacrylated gelatin (GelMA) hydrogels, we studied the effects of the neural cells (PC12) on the formation and maturation of muscle tissues. Myoblasts cultured in the presence of neural cells showed improved differentiation, with enhanced myotube formation. Myotube alignment, length and coverage area were increased. In addition, the mRNA expression of muscle differentiation markers (Myf-5, myogenin, Mefc2, MLP), muscle maturation markers (MHC-IId/x, MHC-IIa, MHC-IIb, MHC-pn, α-actinin, sarcomeric actinin) and the neuromuscular markers (AChE, AChR-ε) were also upregulated. All these observations were amplified after further muscle tissue maturation under electrical stimulation. Our data suggest a synergistic effect on the C2C12 differentiation induced by PC12 cells, which could be useful for creating improved muscle tissue. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Tissue Engineering and Regenerative Medicine 11/2014; DOI:10.1002/term.1956 · 5.20 Impact Factor

Publication Stats

6k Citations
1,224.94 Total Impact Points


  • 1979-2015
    • Tohoku University
      • • Graduate School of Environmental Studies
      • • Department of Bioengineering and Robotics
      • • Department of Biomolecular Engineering
      • • Department of Chemical Engineering
      • • Department of Applied Chemistry
      Miyagi, Japan
  • 2011
    • National Institute for Environmental Studies
      Tsukuba, Ibaraki, Japan
  • 2009
    • University of Hyogo
      • Graduate School of Material Science
      Kōbe, Hyōgo, Japan
  • 1987
    • University of Delaware
      • Department of Chemistry and Biochemistry
      Ньюарк, Delaware, United States
  • 1984-1985
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States