Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10544-020-00505-4

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Other Link： http://link.springer.com/article/10.1007/s10544-020-00505-4/fulltext.html

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

A totally transparent subdural electrode was developed by embedding a conductive poly (vinyl alcohol) (PVA)-filled microchannel made of poly(dimethylsiloxane) (PDMS) into an another PVA hydrogel substrate. Tight bonding between the PVA substrate and the PDMS microchannel (salt bridge) was achieved by mechanical interlocking utilizing the microprotrusions formed on the microchannel. This simple method of bonding without the use of any additives such as silane molecules or nanofibers is very suitable for constructing biomedical devices. The salt bridge electrode (total thickness, ca. 1.5 mm) was sufficiently soft, and showed superior shape conformability that makes it an excellent choice as a subdural electrode used on the brain surface. In vivo measurement proved that the salt bridge electrode makes close contact to the exposed porcine brain and can record brain wave signals of frequencies 1 ~ 15 Hz. In addition, the high transparency of the electrode provided a clear view of the brain surface that would assist the effective surgical operation and optogenetic research.

DOI： 10.1007/s10544-020-00517-0

PubMed

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

DOI： 10.1021/acsaelm.9b00671

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

DOI： 10.1002/admt.201900889

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

A totally soft organic subdural electrode has been developed by embedding an array of poly(3,4-ethylenedioxythiophene)-modified carbon fabric (PEDOT-CF) into the polyvinyl alcohol (PVA) hydrogel substrate. The mesh structure of the stretchable PEDOT-CF allowed stable structural integration with the PVA substrate. The electrode performance for monitoring electrocorticography (ECoG) was evaluated in saline solution, on ex vivo brains, and in vivo animal experiments using rats and porcines. It was demonstrated that the large double-layer capacitance of the PEDOT-CF brings low impedance at the frequency of brain wave including epileptic seizures, and PVA hydrogel substrate minimized the contact impedance on the brain. The most important unique feature of the hydrogel-based ECoG electrode was its shape conformability to enable tight adhesion even to curved, grooved surface of brains by just being placed. In addition, since the hydrogel-based electrode is totally organic, the simultaneous ECoG-fMRI measurements could be conducted without image artifacts, avoiding problems induced by conventional metallic electrodes.

DOI： 10.1038/s41598-019-49772-z

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

DOI： 10.1371/journal.pone.0219198

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

DOI： 10.1115/1.4043522

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

A hydrogel-based microchamber with organic electrodes for efficient electrical stimulations of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is described. The microchamber is made from molecularly permeable, optically transparent, and electrically conductive polyvinyl alcohol (PVA) hydrogel and highly capacitive carbon electrode modified with poly(3,4-ethylenedioxythiophene) (PEDOT). Spheroids of hiPSC-CMs are cultured in microchambers, and electrically stimulated by the electrode for maturation. The large interfacial capacitance of the electrodes enables several days of electrical stimulation without generation of cytotoxic bubbles even when the electrodes are placed near the spheroids. The spheroids can be cultivated in the closed microchambers because of the permeated nutrients through the hydrogel, thus the spheroids are stably addressable and the culture medium around the sealed microchambers can be simply exchanged. Synchronized beating of the spheroids can be optically analyzed in situ, which makes it possible to selectively collect electrically responsive cells for further use. As the hydrogel is electrically conductive, the amount of electrical charge needed for maturing the spheroids can be reduced by configuring electrodes on the top and the bottom of the microchamber. The bioreactor will be useful for efficient production of matured hiPSC-CMs for regenerative medicine and drug screening.

DOI： 10.1002/mabi.201900060

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

This paper addresses a nanoengineering approach to create a fully three-dimensional (3D) network of living cells, providing an advanced solution to in vitro studies on either neuronal networks or artificial organs. The concept of our work relies on stackable scaffolds composed of microcontainers designed and dimensioned to favor the geometrically constrained growth of cells. The container geometry allows cells to communicate in the culture medium and freely grow their projections to form a 3D arrangement of living cells. Scaffolds are fabricated using two-photon polymerization of IP-L 780 photoresist and are coated with collagen. They are stacked by mechanical micromanipulation. Technical details of the proposed nanofabrication scheme and assembly of the modular culture environment are explained. Preliminary in vitro results using PC12 cells have shown that this structure provides a good basis for healthy cell growth for at least 16 days. Our approach is envisioned to provide tailor-made solutions of future 3D cell assemblies for potential applications in drug screening or creating artificial organs.

DOI： 10.1039/c8lc01240g

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

A totally organic and disposable electrochromic timer integrated with an enzymatic electrode and powered by biofuel cells is developed. The cathode of the self-powered electrochromic timer consists of a composite electrochromic film of poly(3,4-ethylenedioxythiophene) (PEDOT) and polyurethane (PU), while the anode is made up of a fructose dehydrogenase (FDH) enzymatic electrode. The electrochromic changes over time (up to 100 min) can be displayed in the device, and the speed of color change can be controlled by changing the resistance between the anode and the cathode. Automatic activation of the timer after placement on a skin is achieved by integrating a porous microneedle array. The electrochromic timer would be used along with a skin patch as a time-lapse display of medical and cosmetic treatments.

DOI： 10.1016/j.bios.2018.07.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MARY ANN LIEBERT, INC  

We propose a pneumatic bending actuator integrated with a low-melting-point alloy-based variable stiffness endoskeleton that can bend at multiple points and maintain its bent shape without power supply. Local stiffness of the soft actuator can be altered by melting or hardening the endoskeleton with electric heat applied through embedded metal wires. Bending points of the actuator can be changed by selecting different points of the endoskeleton to be melted, and the bending angle can be controlled by injected air pressure. The shape of the bent actuator is maintained by hardening the alloy even when pressure is reduced to the initial state. We demonstrate that the actuator can be bent differently with only one pneumatic actuation layer by combining multipoint bending and the shape retention function, and thus the actuator can be used for lifting, holding, and unloading an object. We believe that the simple machinery of the actuator will be useful in programming complicated motions of soft robotic fingers, fins, and tentacles.

DOI： 10.1089/soro.2017.0145

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

Engineering of neuronal network geometry by micropatterning technology is a key future technology for creating artificial brains on a chip. However, engineering of network geometry at the single-cell-level with functional morphology (axon/dendrite) and connectivity (synapses) is still challenging. Here, we describe a method for controlling the axon and dendrite morphology of single primary-cultured neurons and assembling a neural circuit using mobile microplates. The microplates enabled morphological control of neurons by their shapes and bringing their ends into contact caused the formation of physical connections. Functional synapse formation at the connection was indicated by immunostaining of synapse-related proteins and intracellular Ca2+ imaging of neural activity. We believe that the method will be useful in engineering neural circuits with selected neurons and defined morphology.

DOI： 10.3390/mi9050235

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Language：English  

Using traditional 2-D photolithographic methods, surface patterns are made on agarose and used to form lipid vesicles with controlled size and layout. Depending on the size and layout of the patterned structures, the lipid bilayer vesicle size can be tuned and placement can be predetermined. Vesicles formed on 2-D patterned surfaces can be harvested for further investigations or can be assayed directly on the patterned surface. Lipid vesicles on the patterned surface are assayed for unilamellarity and protein incorporation, and vesicles are indeed unilamellar as observed from outer leaflet fluorescence quenching. Vesicles successfully incorporate the integral membrane protein α-hemolysin and maintain its membrane transport function.

DOI： 10.1063/1.5002604

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

DOI： 10.1088/0960-1317/26/9/095017

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DOI： 10.1002/adhm.201500782

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/smll.201502968

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOP PUBLISHING LTD  

This paper describes a liquid-filled tunable lenticular lens for switching between two-dimensional (2D) and three-dimensional (3D) images in naked-eye 3D displays. Compared with previous 2D/3D switchable displays, this tunable lenticular lens that is directly attached to a smartphone display can project both a 2D image with the original resolution of the smartphone display and a 3D image with high brightness. This lens is simply composed of transparent poly(dimethylsiloxane) (PDMS) microchannels. While the thin top membrane on the microchannels is normally flat to transmit light without deflection for displaying 2D images, applying pressure to the microchannel deforms the membrane to acquire characteristics of lenticular lenses for 3D images. We successfully demonstrate the switching between the 2D and 3D modes. We believe that our lens can be applied as a part of a portable 2D/3D naked-eye 3D display.

DOI： 10.1088/0960-1317/25/3/035030

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DOI： 10.20965/ijat.2014.p0095

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

We compare the generalization characteristics of complex-valued and real-valued feedforward neural networks. We assume a task of function approximation with phase shift and/or amplitude change in signals having various coherence. Experiments demonstrate that complex-valued neural networks show smaller generalization error than real-valued networks having doubled input and output neurons in particular when the signals have high coherence, that is, high degree of wave nature. We also investigate the relationship between amplitude and phase errors. It is found in real-valued networks that abrupt change in amplitude is often accompanied by steep change in phase, which is a consequence of local minima in real-valued supervised learning.

DOI： 10.1007/s00521-012-0960-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC  

Applications of complex-valued neural networks (CVNNs) have expanded widely in recent years-in particular in radar and coherent imaging systems. In general, the most important merit of neural networks lies in their generalization ability. This paper compares the generalization characteristics of complex-valued and real-valued feedforward neural networks in terms of the coherence of the signals to be dealt with. We assume a task of function approximation such as interpolation of temporal signals. Simulation and real-world experiments demonstrate that CVNNs with amplitude-phase-type activation function show smaller generalization error than real-valued networks, such as bivariate and dual-univariate real-valued neural networks. Based on the results, we discuss how the generalization characteristics are influenced by the coherence of the signals depending on the degree of freedom in the learning and on the circularity in neural dynamics.

DOI： 10.1109/TNNLS.2012.2183613

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Language：English   Book type：Scholarly book

This paper introduces a new technique for patterning functionalization layers on substrates with hightopogra phy. The method is based on a parylene-C template shaped by a structured, sacrificial photoresist layer and attached to the substrate where functionalization is not intended. After photoresist removal and surface function ali za tion, the parylene layer is peeled off, leaving all areas initially covered by the sacrificial polymer functionalized. The technique has several advantages: （i） In contrast to microcontact printing, it allows surfaces with complex topographies to be functionalized; （ii） complex function al ization patterns are possible; （iii） the parylene structure can be reutilized. We successfully demonstrate the technique with the guided growth of neuron-like PC12 cells on honeycomb-shaped protein patterns on micro pillars and microwells. The range and limits of the technique are analyzed and discussed in detail.

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Language：Japanese   Presentation type：Poster presentation   Country：Japan  

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Event date： 2020 　 　

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Event date： 2019.10 　 　

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Event date： 2018.12 　 　

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Event date： 2018.11 　 　

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We propose a bioactuator driven by a chick embryo cardiomyocyte for the investigation of cardiomyocytes as alternatives of rodent cardiomyocytes driven actuator. Chick embryo cardiomyocytes are more accessible than rodent cardiomyocytes in terms of cost and ethics. Here, we cultured chick embryo cardiomyocytes on parylene films and observed that the edges of parylene films were autonomously lifted up and down by the contractile force of cardiomyocytes. Moreover, the frequency of flapping increased in response to the addition of isoproterenol, which promotes contraction of cardiac muscles. This bioactuator would reduce the cost of experiments and thus be expected to promote the study of contractile properties of cardiomyocytes.

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In this paper, we report a microfluidic device for pairing uniformly sized liposomes and fusing the paired liposomes. Our microfluidic device is composed of dynamic micro array for pairing liposomes and three-dimensional electrode for fusing liposomes. Electrodes should be located in proper position of a dynamic micro array for applying sufficient electric field to fuse liposomes. By using low melting point alloy, 3D electrodes were integrated in the dynamic microarray device to fuse the paired liposomes. Two uniformly sized liposomes were successfully paired in the dynamic micro array device and fused by the integrated 3D electrode. We believe that this dynamic micro array device will become a useful microfluidics device for vesicle fusion.

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This manuscript describes selective electrofusion of cell-sized liposomes using microfabricated dielectrophoretic tweezer. We fabricated round-tip dielectrophoretic tweezers by microfabrication techniques. We enabled selective manipulation of liposomes by applying alternate current to the tweezer. As we control the frequency of the current, we attract or repulse the liposomes. Liposomes were selectively manipulated one-by-one and paired by the tweezers. Finally we paired two cell-sized liposomes in a hand-made electrofusion chamber by using the tweezer. The paired liposomes were contact with each other by applying alternate current, then fused by pulses of direct current. We believe our technique will be useful in liposome and cell fusion study for artificial cell research.

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Event date： 2017.7 　 　

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In this paper, we developed a centrifugal emulsification device toward high-throughput generation of monodisperse liposomes. The device generated lipid vesicles in two steps, membrane emulsification by asymmetric through-holes on a plate, and transfer of the emulsions to a planar monolayer at an oil/water interface. As a result of centrifugation of the device in a microtube, we succeeded in collection of cell-sized lipid vesicle. Since a number of the asymmetric through-holes can be fabricated on the plate by standard photolithographic process, and the reservoir for inner solution has relatively large volume (40 μl), the proposed device will be a powerful tool for massive generation of liposomes.

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Event date： 2017.1 - 　

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Event date： 2016.1 　 　

We propose a method to assemble fiber-shaped tissues into a 3D network. In the method, we connected fiber-shaped tissues using micro pillar devices anchoring both ends of the tissues. The fibershaped tissues were assembled into heterogeneous and 3D network. We believe that this method will be useful for the analysis of cellular morphology and functions in a 3D network of tissues.

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Event date： 2016 　 　

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This paper reports a system enabling cell detection, fluorescence light detection and single cell retrieval. It consists of a device combining a microplate technology, allowing single cell seeding on individual cell-sized paiylene plates, and a CMOS imaging sensor placed on the right bottom of the microplate chip with glass substrate. By using such a system, we succeeded to visualize individual cells, to detect fluorescence light emission and to retrieve a single cell by using a micromanipulator. We believe that the proposed system will be useful for the point of care analysis on the level of single cell analysis.

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Event date： 2014.1 　 　

© 14CBMS. We describe a centrifuge-based dynamic microarray system for trapping an array of single cells from small amount of suspension. We optimized microchannel designs and centrifugal force for minimizing sample volumes and maximizing trapping efficiencies, and achieved single-cell trapping by introducing only 5 μl of cell suspension with the centrifugal force of 70 G. Trapping of cells stained with DAPI shows that single cells were trapped at desired trapping spots. This system will be applicable for single cell assays using rare or expensive cells.

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Event date： 2013.11 　 　

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Event date： 2013.11 　 　

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We achieved three-dimensional (3D) fabrication of heterogeneous microstructures using an in situ photo-polymerization method, vertical continuous flow lithography (VCFL). Utilizing a projection system including a Digital Mirror Device, 3D microstructures were fabricated in a layer-by-layer fashion with the thickness of each layer controlled by UV absorber and exposure time. In addition, VCFL fabricated heterogeneous microstructures by exposing light patterns to multiple laminar flows. We demonstrated three-layered structures and long fibers whose cross-sectional geometries were changed. We also fabricated two-layered Janus structures. We believe that VCFL will be applicable to making anisotropic microparticles for material science and bottom up tissue engineering.

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Event date： 2013 　 　

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This paper describes a tunable lenticular lens to switch high-resolution two-dimensional (2D) / three-dimensional (3D) images in naked-eye stereoscopic displays. This lens is simply composed of transparent poly(dimethylsiloxane) (PDMS) microchannels and pumps to realizes two states: (A) flat surface for light transmissions without deflection
(B) cylindrically deformed surface for light deflection. This lens has three advantages: (i) switchable optical characteristics without patterned electrode, (ii) adjustable focal length by the pressure-driven deformation, (iii) simple fabrication and low-cost experimental setup. By using this device put on a Smart Phone display, we successfully observed 3D images and two different images depending on view angle. Moreover, we obtained clear 2D images without decrease in the horizontal resolution. We believe that this device can be applied to a portable and high luminance naked-eye stereoscopic display by the combination with various types of commercially available portable displays. © 2013 IEEE.

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This paper compares the generalization characteristics of complex-valued and real-valued feedforward neural networks in terms of coherence of signals to be dealt with. We assume a task of function approximation such as interpolation of temporal signals. Simulation and real-world experiments demonstrate that complex-valued neural networks with amplitude-phase-type activation function show smaller generalization error than real-valued networks such as bivariate and dual-univariate real-valued neural networks. Based on the results, we discuss how the generalization characteristics are influenced by the coherence of the signals depending on the degree of freedom in the learning and on the circularity in neural dynamics.

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