Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

The present study was performed to establish a novel ocular surgery simulator for training in peeling of the inner limited membrane (ILM). This simulator included a next-generation artificial ILM with mechanical properties similar to the natural ILM that could be peeled underwater in the same manner as in actual surgery. An artificial eye consisting of a fundus and eyeball parts was fabricated. The artificial eye was installed in the eye surgery simulator. The fundus part was mounted in the eyeball, which consisted of an artificial sclera, retina, and ILM. To measure the thickness of the fabricated ILM on the artificial retina, we calculated the distance of the step height as the thickness of the artificial ILM. Two experienced ophthalmologists then assessed the fabricated ILM by sensory evaluation. The minimum thickness of the artificial ILM was 1.9 ± 0.3 μm (n = 3). We were able to perform the peeling task with the ILM in water. Based on the sensory evaluation, an ILM with a minimum thickness and 1000 degrees of polymerization was suitable for training. We installed the eye model on an ocular surgery simulator, which allowed for the performance of a sequence of operations similar to ILM peeling. In conclusion, we developed a novel ocular surgery simulator for ILM peeling. The artificial ILM was peeled underwater in the same manner as in an actual operation.

DOI： 10.1371/journal.pone.0196131

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

We propose a novel on-chip 3D cell rotation method based on a vibration-induced flow. When circular vibration is applied to a microchip with micropillar patterns, a highly localized whirling flow is induced around the micropillars. The direction and velocity of this flow can be controlled by changing the direction and amplitude of the applied vibration. Furthermore, this flow can be induced on an open chip structure. In this study, we adopted a microchip with three micropillars arranged in a triangular configuration and an xyz piezoelectric actuator to apply the circular vibration. At the centre of the micropillars, the interference of the vibration- induced flows originating from the individual micropillars induces rotational flow. Consequently, a biological cell placed at this centre rotates under the influence of the flow. Under three-plane circular vibrations in the xy, xz or yz plane, the cell can rotate in both the focal and vertical planes of the microscope. Applying this 3D cell rotation method, we measured the rotational speeds of mouse oocytes in the focal and vertical planes as 63.7 +/- 4.0 degrees s(-1) and 3.5 +/- 2.1 degrees s(-1), respectively. Furthermore, we demonstrated the transportation and rotation of the mouse oocytes and re-positioned their nuclei into a position observable by microscope.

DOI： 10.1038/micronano.2015.1

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

Cell manipulations and cell surgeries are key techniques in biotechnology today. Micro/nanorobots integrated on a microfluidic chip (on-chip robot) are a promising technology for cell manipulations and cell surgeries because of their operator skill independency and robustness for external environments. These features enable high-throughput cell manipulations and cell surgeries on a microfluidic chip. However, it is difficult to apply previous on-chip robots for small cells of order approximate to 10 mu m because the manipulation or surgery probes of those robots are a few micrometers in size. This size has been restricted by their fabrication, employing a standard mask lithography process. We fabricated on-chip robots of nanometer size by femtosecond laser exposure (nanorobots). The processing resolutions were 270 nm (linewidth) and 600 nm (thickness). Furthermore, our fabrication technique enabled the nanorobot to have a hybrid structure integrating functional nanomaterials (hybrid nanorobot). By integrating the various functional nanomaterials on the nanorobot, we can create a new function for the nanorobot. In this study, we fabricated a hybrid nanorobot with carbon nanotubes (CNTs) of high photothermal efficiency. We demonstrated a single-cell puncture with this nanorobot by irradiating the CNTs with an infrared laser and generating heat at that point. Additionally, we demonstrated an optical manipulation of the nanorobot that makes it possible to perform a cell puncture with high spatial flexibility and high positioning accuracy.

DOI： 10.1109/TRO.2013.2284402

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

Enhanced mixing in microfluidic systems is necessary in many applications such as chemical processing, biological assays, and diagnosis. We are developing a microfluidic system to efficiently mix minute reagents (down to several microliters) using vibration-induced flow (VIF), in which a net flow is generated around a micropillar by applying periodic vibration. In this study, we numerically investigate the enhancement in chaotic mixing using the VIF technique and periodic switching of vibrations. By extending our previous numerical simulation model, we investigate the flow field and trajectories of fluid particles in three-dimensional space. We demonstrate that chaotic advection characteristics can be observed by periodically switching the vibrational direction of a substrate using simple cylindrical pillars. In addition, using an appropriate interval for switching the vibration axes yields better mixing performance. The extent of chaotic advection is evaluated quantitatively using the Lyapunov exponent considering various vibration parameters, such as the vibration amplitude, separation distance between each pillar and pillar shape. The flow field induced by a large-amplitude and sharp-edged wall pillar provides excellent mixing results. Thus, VIF is successfully applied to obtain an efficient mixing strategy with the aid of the chaotic theory.

DOI： 10.1063/5.0192387

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

Vibration-induced flow (VIF), in which a mean flow is induced around a microstructure by applying periodic vibrations, is increasingly used as an active flow-control technique at the microscale. In this study, we have developed a microdevice that actively controls the VIF patterns using elastic membrane protrusions (microballoons) actuated by pneumatic pressure. This device enables on-demand spatial and temporal fluid manipulation using a single device that cannot be achieved using a conventional fixed-structure arrangement. We successfully demonstrated that the device achieved displacements of up to 38 µm using the device within a pressure range of 0 to 30 kPa, indicating the suitability of the device for microfluidic applications. Using this active microballoon array, we demonstrated that the device can actively manipulate the flow field and induce swirling flows. Furthermore, we achieved selective actuation of the microballoon using this system. By applying air pressure from a multi-input channel system through a connection tube, the microballoons corresponding to each air channel can be selectively actuated. This enabled precise control of the flow field and periodic switching of the flow patterns using a single chip. In summary, the proposed microdevice provides active control of VIF patterns and has potential applications in advanced microfluidics, such as fluid mixing and particle manipulation.

DOI： 10.3390/mi14112010

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/sii55687.2023.10039404

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/mems49605.2023.10052379

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/mems49605.2023.10052310

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society of Mechanical Engineers  

DOI： 10.1299/mej.22-00223

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE COMPUTER SOC  

In this study, we fabricated three-dimensional (3D) DEA made of an organogel and drove it out-of-plane direction using an experimental system that applied pre-stretch with water pressure. Organogels have a lower Young's modulus and higher relative permittivity than elastomer materials used in conventional DEA such as PDMS. Therefore, fabrication of DEAs using organogel is expected to increase the displacement of DEAs. Thus, we fabricated a dielectric gel that is a kind of organogel with high dielectric constant and excellent elasticity. We evaluated static characteristics and frequency response of water-pre-stretched DEA made of dielectric gel. We also fabricated three-dimensional dielectric gel for a 3D shaped DEA. From a driving experiment, it was confirmed that this 3D DEA can generate 10 times larger displacement than that of PDMS.

DOI： 10.1109/SII55687.2023.10039186

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE COMPUTER SOC  

In this paper, we analyzed dynamic characteristics of a balloon-type dielectric elastomer actuator (DEA) prestretched by water pressure. We derived an analytical solution for dynamic characteristics of this DEA based on a physical model of this experimental system. This experimental system consists of an elastomer attached on an acrylic pipe and a water reservoir connected to the acrylic pipe with a hose. Therefore, by changing parameters of these equipment, dynamic characteristics will be changed. We analyzed frequency response of the DEA when we changed these parameters and compared experimental values with theoretical values. Also, we analyzed dynamic responses when various electric voltages were applied to the DEA. The analytical solution can predict frequency responses and dynamic response. In addition, we conducted open loop control of displacement of the DEA. Deformations of DEA was able to be controlled according to desired displacement with the constructed model.

DOI： 10.1109/SII55687.2023.10039139

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/mhs56725.2022.10092047

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/mhs56725.2022.10091984

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/mhs56725.2022.10092187

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

We present a microgripper actuated by a soft microactuator for manipulating a single living cell. Soft actuators have attracted attention in recent years because their compliance which can adapt to soft targets. In this study, we propose a microgripper actuated by soft thermoresponsive hydrogels. The thermoresponsive gel swells in water when the temperature is low and shrinks when the temperature is high. Therefore, the microgripper can be driven by controlling the temperature of the thermoresponsive gel. The gels are actuated by irradiating with infrared (IR) laser to localize heating. The actuation characteristics of the gripper were theoretically analyzed and we designed a gripper that gripped a ≈10 µm size cell. Additionally, we succeeded in actuating the fabricated microgripper with laser irradiation and gripping a single living cell.

DOI： 10.3390/mi13050794

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

DOI： 10.1109/nems54180.2022.9791090

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer  

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Authorship：Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本ロボット学会  

Soft robots have been attracting a lot of attentions in recent years because they have completely different characteristics from conventional robots having rigid structures. We have proposed a soft microrobot using a thermoresponsive gel as a soft actuator. This robot can be driven by being irradiated with light for controlling its temperature. In this study, we drive a robot having three gel actuators with a straight shape with peristaltic motion by scanning the robot with a laser. We evaluated actuation timing of each actuator and a displacement of the robot during the peristaltic motion.

DOI： 10.7210/jrsj.40.83

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本ロボット学会  

On-chip actuator is an essential component to realize single cell analysis in microfluidic device. Previously, we proposed a light-driven gel actuator for single cell manipulations. The advantage of this drive method is it enables local heating for integration of large number of actuators on a microfluidic chip. In this study, we present multiple cell manipulations system by using integrated light-driven gel actuators. We construct the microscope to irradiate patterned light by using digital mirror device. Therefore, we can drive multiple gel actuators selectively. Finally, we demonstrate an example of cell manipulations by using integrated gel actuators and the constructed system.

DOI： 10.7210/jrsj.39.673

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Authorship：Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本ロボット学会  

Previously, we proposed new light irradiation-based drive method of on-chip gel actuator. In our method, on-chip gel actuators are fixed on a glass substrate with light absorbers. Therefore, deformation of the gel is constricted with fixed part and anisotropically deforms in three dimensions. In this study, we evaluate the three-dimensional shapes and drive characteristics of on-chip gel actuator. Furthermore, we evaluate changes of drive characteristics of the actuators with respect to surface area to volume ratio. From this result, we show the possibilities of control of gel deformation and drive characteristics by changing the design of the proposed gel actuator.

DOI： 10.7210/jrsj.39.565

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer  

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We present a micro-gelrobot driven by irradiation of a laser. The proposed micro-gelrobot mimics living organisms and moves by peristaltic motion. In this paper, we show the micro-gelrobot has multiple soft structures and rigid structures. The soft structures work as actuators like muscles and rigid strictures work as supporting bodies like skeletons. As rigid structures, SU-8 which is hard photoresist is used. As soft actuators, bioresist which is a photo-patternable temperature-responsive gel is used. Bioresist swells by absorbing water at lower temperature than 32 degrees C and shrinks by releasing water at higher temperature than 32 degrees C. Thus, we use this changing volume as a displacement of an actuator. In addition, we mixed bioresist with graphene as light absorber to actuate this gel actuator by near infrared laser irradiation. The proposed micro-gelrobot is fabricated by using photolithography which is a common MEMS fabrication process. Additionally, fabrication process of the proposed micro-gelrobot include release process of the robot from the glass substrate. For release of micro-gelrobot, we use sacrificial layer made of dextran which is a kind of polysaccharide. We use digital mirror device (DMD) to irradiate patterned light to actuate multiple gel actuators. We succeeded in driving the proposed micro-gelrobot using laser scanning. In addition, we evaluate a displacement of the peristaltic motion. The proposed micro-gelrobot can move forward by performing a peristaltic motion.

DOI： 10.1109/ieeeconf49454.2021.9382636

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We propose drive method of on-chip gel actuator using light irradiation for massive integration of gel actuators. The gel actuator is made of temperature responsive gel and patterned on a chip with light absorbing material. Thus, it can be driven by irradiation of light to control its temperature. By using this method, we can selectively drive an actuator among massively integrated actuators by irradiating patterned light and it can be applied to high-throughput cell manipulations. In this study, we demonstrated an example of cell manipulation by using this method. We made a flow channel for cell transportation by irradiating light. We succeeded in making straight channel by irradiating actuators with sheet laser. In this channel, we observed that motile cells moved and we succeeded in trapping the motile cells by turning off the laser and swelling the actuators.

DOI： 10.1109/mems46641.2020.9056395

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Language：English  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41596-019-0252-5

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGERNATURE  

<jats:title>Abstract</jats:title>
<jats:p>This paper presents fabrication and actuation methods for a soft microrobot with a hybrid structure composed of soft microactuators and a rigid supporting body. This hybrid structure enables actuation of the microrobot with independent driving of multiple actuators to provide complex movement like that of living microorganisms. We use the temperature-responsive hydrogel poly(<jats:italic>N</jats:italic>-isopropylacrylamide) (PNIPAAm) as a soft microactuator. PNIPAAm swells with water at low temperature but shrinks at high temperature. This volume change thus allows PNIPAAm to be used as an actuator by controlling its temperature. We successfully fabricated the microrobot with its soft-rigid hybrid structure composed of PNIPAAm and rigid photoresist using a multilayered microfabrication process. In addition, we used a sacrificial layer process to release the fabricated microrobot from the substrate to allow it to move freely. To actuate the microrobot, we mixed PNIPAAm with graphene, which has a high photothermal conversion efficiency. The temperature of the soft actuator when mixed with graphene can be increased by irradiating it with light. Therefore, actuation of the microrobot is achieved by sequentially irradiating the microactuators with focused light. We present the fabrication, release and partial actuation of the microrobot to demonstrate the feasibility of the proposed microrobot with the soft-rigid hybrid structure in this paper.</jats:p>

DOI： 10.1186/s40648-019-0140-3

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

<p>We demonstrate an on-chip microparticle sorter with an ultrashort switching window using femtosecond laser pulses to overcome the fundamental limitation of the sorting performance described by Poisson statistics.</p>

DOI： 10.1039/c9lc00324j

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

Intelligent image-activated cell sorting (iIACS) is a machine-intelligence technology that performs real-time intelligent image-based sorting of single cells with high throughput. iIACS extends beyond the capabilities of fluorescence-activated cell sorting (FACS) from fluorescence intensity profiles of cells to multidimensional images, thereby enabling high-content sorting of cells or cell clusters with unique spatial chemical and morphological traits. Therefore, iIACS serves as an integral part of holistic single-cell analysis by enabling direct links between population-level analysis (flow cytometry), cell-level analysis (microscopy), and gene-level analysis (sequencing). Specifically, iIACS is based on a seamless integration of high-throughput cell microscopy (e.g., multicolor fluorescence imaging, bright-field imaging), cell focusing, cell sorting, and deep learning on a hybrid software-hardware data management infrastructure, enabling real-time automated operation for data acquisition, data processing, intelligent decision making, and actuation. Here, we provide a practical guide to iIACS that describes how to design, build, characterize, and use an iIACS machine. The guide includes the consideration of several important design parameters, such as throughput, sensitivity, dynamic range, image quality, sort purity, and sort yield; the development and integration of optical, microfluidic, electrical, computational, and mechanical components; and the characterization and practical usage of the integrated system. Assuming that all components are readily available, a team of several researchers experienced in optics, electronics, digital signal processing, microfluidics, mechatronics, and flow cytometry can complete this protocol in ~3 months.

DOI： 10.1038/s41596-019-0183-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATL ACAD SCIENCES  

Combining the strength of flow cytometry with fluorescence imaging and digital image analysis, imaging flow cytometry is a powerful tool in diverse fields including cancer biology, immunology, drug discovery, microbiology, and metabolic engineering. It enables measurements and statistical analyses of chemical, structural, and morphological phenotypes of numerous living cells to provide systematic insights into biological processes. However, its utility is constrained by its requirement of fluorescent labeling for phenotyping. Here we present label-free chemical imaging flow cytometry to overcome the issue. It builds on a pulse pair-resolved wavelength-switchable Stokes laser for the fastest-to-date multicolor stimulated Raman scattering (SRS) microscopy of fast flowing cells on a 3D acoustic focusing microfluidic chip, enabling an unprecedented throughput of up to similar to 140 cells/s. To show its broad utility, we use the SRS imaging flow cytometry with the aid of deep learning to study the metabolic heterogeneity of microalgal cells and perform marker-free cancer detection in blood.

DOI： 10.1073/pnas.1902322116

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

In recent years, soft robots are attracting attention. The important point of fabrication of soft robot is mimicking soft-rigid hybrid structures like living organisms. Most of soft robots reported are in macro-scale, but soft microrobot has not been reported much. To realize soft microrobot, we propose micro-gel robots having a soft-rigid hybrid structure in this study. The soft parts are made from thermoresponsive gel actuator and it can be actuated by irradiating laser on it. The rigid parts are made of SU-8 that supports entire body of the micro-gel robot. This hybrid structure of the soft and rigid materials can realize complicated motion like living organisms. We succeeded in fabrication of the proposed micro-gel robot by using sacrificial layer process. Furthermore, we performed proof of concept of the actuation of the robot with laser irradiation.

DOI： 10.1109/transducers.2019.8808823

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC ADVANCEMENT SCIENCE  

Flow cytometry is an indispensable tool in biology for counting and analyzing single cells in large heterogeneous populations. However, it predominantly relies on fluorescent labeling to differentiate cells and, hence, comes with several fundamental drawbacks. Here, we present a high-throughput Raman flow cytometer on a microfluidic chip that chemically probes single live cells in a label-free manner. It is based on a rapid-scan Fourier-transform coherent anti-Stokes Raman scattering spectrometer as an optical interrogator, enabling us to obtain the broadband molecular vibrational spectrum of every single cell in the fingerprint region (400 to 1600 cm(-1)) with a record--high throughput of similar to 2000 events/s. As a practical application of the method not feasible with conventional flow cytometry, we demonstrate high-throughput label-free single-cell analysis of the astaxanthin productivity and photosynthetic dynamics of Haematococcus lacustris.

DOI： 10.1126/sciadv.aau0241

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

We demonstrated the applicability of the vibration-induced flow, in which a mean flow is induced around a micro-pillar by applying small circulating vibration (Figure 1), for capturing small particles by larger capture beads. The current approach is advantageous in handling a small amount of liquid of down to several \\mu \\mathrm{L} because it does not require an external pump. A set of capturing experiments implemented with a simple cylindrical pillar showed that the capturing-rate of small particles depends on the vibration parameters. Since the binding energy (affinity) of biological samples is often weak, there exists the optimal condition to achieve a high capturing rate.

DOI： 10.1109/memsys.2019.8870689

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Chemical and Biological Microsystems Society  

In this study, we propose driving method of on-chip gel actuator by using light irradiation. The proposed method enables local heating of temperature responsive gel actuators and independent driving of a single actuator above multiple actuators. Therefore, the proposed method realizes to put multiple actuators at short distance. In this study, we demonstrated trapping and mechanical stimulation to Euglena as an example of cell manipulations. The proposed driving method will realize high-throughput and various single cell manipulations on a chip.

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Chemical and Biological Microsystems Society  

We propose on-chip micromixer with low dead volume based on vibration-induced flow. Vibration-induced flow is the local flow which is induced around a microstructure by applying high-speed vibration to the structure. The important characteristic of this flow is it can be induced without external pumps. Therefore, dead volume existing in the tube connection parts of conventional micromixer can be omitted. Thus, the proposed method is suitable for mixing of rare samples, such as expensive fluorescent reagent or antibodies. In this study, we quantitatively evaluated mixing performance of the proposed method by using variance of microparticle distance.

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

The steady streaming (SS) phenomenon is gaining increased attention in the microfluidics community, because it can generate net mass flow from zero-mean vibration. We developed numerical simulation and experimental measurement tools to analyze this vibration-induced flow, which has been challenging due to its unsteady nature. The validity of these analysis methods is confirmed by comparing the three-dimensional (3D) flow field and the resulting particle trajectories induced around a cylindrical micro-pillar under circular vibration. In the numerical modeling, we directly solved the flow in the Lagrangian frame so that the substrate with a micro-pillar becomes stationary, and the results were converted to a stationary Eulerian frame to compare with the experimental results. The present approach enables us to avoid the introduction of a moving boundary or infinitesimal perturbation approximation. The flow field obtained by the micron-resolution particle image velocimetry (micro-PIV) measurement supported the three-dimensionality observed in the numerical results, which could be important for controlling the mass transport and manipulating particulate objects in microfluidic systems.

DOI： 10.3390/mi9120668

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

In recent years, soft robots attracting large attention. We aim to realize a microrobot capable of complicated movement mimicking living microorganisms. In this study, we propose a soft microgel robot that can perform peristaltic motion driven by light irradiation.

DOI： 10.1109/mhs.2018.8887065

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/mhs.2018.8886934

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OPTICAL SOC AMER  

Label-free particle analysis is a powerful tool in chemical, pharmaceutical, and cosmetic industries as well as in basic sciences, but its throughput is significantly lower than that of fluorescence-based counterparts. Here we present a label-free single-particle analyzer based on broadband dual-comb coherent Raman scattering spectroscopy operating at a spectroscopic scan rate of 10 kHz. As a proof-of-concept demonstration, we perform broadband coherent anti-Stokes Raman scattering measurements of polystyrene microparticles flowing on an acoustofluidic chip at a high throughput of >1000 particles per second. This high-throughput label-free particle analyzer has the potential for high-precision statistical analysis of a large number of microparticles including biological cells. (C) 2018 Optical Society of America

DOI： 10.1364/OL.43.004057

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Berlin Heidelberg  

DOI： 10.1007/s10404-018-2062-4

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

DOI： 10.3390/s18020345

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Although researchers have proposed various methods of on-chip cell sorting, high-throughput sorting of large cells remains hampered by the difficulty of controlling high-speed flow over a wide sorting area. To overcome this problem, we proposed high-speed local-flow control using dual membrane pumps driven by piezoelectric actuators placed on the outside of a microfluidic chip in this paper. We evaluated the controllability of shifting the flow profile by the local-flow. The results indicated that we could sort large cells up to approximately 150 mu m in size with an equivalent throughput of 31 kHz. Because our method can control the flow profiles, it is applicable not only to large cells but also to small cells. The cell-sorting efficacy of the proposed method was experimentally evaluated on Euglena gracilis NIES-48 (E. gracilis) cells as large target cells and GCIY-EGFP (GCIY) cells derived from a gastric cancer cell line as small target cells. In E. gracilis cells sorting, the throughput is 23 kHz with a 92.8% success rate, 95.8% purity, and 90.8% cell viability. In GCIY sorting, the throughput is 11 kHz with a 97.8% success rate, 98.9% purity, and 90.7% cell viability. These results confirm that the proposed method sorts differently sized cells with high throughput and hence, overcomes the throughput-size trade-off that exists in conventional on-chip cell sorters.

DOI： 10.1039/c7lc00536a

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

DOI： 10.1109/icra.2017.7989783

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We propose an on-chip cell manipulation method for a parallel trapping of single motile cells. The proposed method enables a parallel trapping of large (&gt;= 50 mu m) motile cells, that is difficult to be achieved with conventional cell manipulation methods. We realize the trapping method by using a vibration-induced flow which is induced by applying a vibration to a microfluidic chip having microstructures on its surface. By applying a rectilinear vibration to a chip with a micropillar array, a localized flow pattern to trap single motile cells are generated around the micropillars. We succeeded in a parallel trapping of single Euglena (size is approximately 50-100 mu m) by using the proposed method. Furthermore, we demonstrated one application of the method for an evaluation of motility of motile cells with a single cell level.

DOI： 10.1109/memsys.2017.7863652

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER INST PHYSICS  

We propose a laser-driven hybrid gel microtool for stable single-cell manipulation. The microtool is made of a microbead dyed with multiwalled carbon nanotubes (MWNT) and thermosensitive poly (N-isopropylacrylamide) gel coating. The gel adheres to cells at high temperatures but not at low temperatures. We can manipulate single cells without direct laser irradiation by adhering the cells to the gel on the microtool using the cell-adhesion property of the gel. The microtool is heated by trapping it with optical tweezers to make its surface cell-adhesive during the manipulation. Furthermore, we can control the optical heating property of the microtool by dyeing the microbeads with MWNT ink. The laser-heating-induced temperature increase of the microtool can be controlled from 4.2 degrees C to 23.5 degrees C by varying the concentration of MWNT ink. We succeeded in fabricating the proposed microtool and demonstrated single-cell transportation using the microtool without direct laser irradiation of the cell. Published by AIP Publishing.

DOI： 10.1063/1.4971827

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

DOI： 10.1109/mhs.2016.7824208

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

We constructed high-speed on-chip local flow control system. The system consists of a microfluidic chip and piezoelectric actuators. The microfluidic chip has microchannels and two membrane pumps. The piezoelectric actuators are set on the membrane pumps, and we can sort cells upward and downward with synchronized actuation of piezo-driven dual membrane pumps. In this research, we demonstrate the on-chip sorting using microbeads.

DOI： 10.1109/mhs.2016.7824192

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

This paper presents the 3D vessel model having a temperature Indicator for evaluating thermal damage during surgery. The materials of model are polydimethylsiloxane (PDMS) and thermochromic dye which indicates color change according to temperature increase. The vessel model is fabricated by dip coating on 3D wax model and lost wax method. However, acetone for removing wax prevents the temperature responsive function of the material. Thus, the surface of the model is coated with protective layer of polyvinyl alcohol (PVA).

DOI： 10.1109/mhs.2016.7824170

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

DOI： 10.1186/s40648-016-0059-x

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Other Link： http://link.springer.com/article/10.1186/s40648-016-0059-x/fulltext.html

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

This paper reports on a training system for internal limiting membrane (ILM) peeling. ILM peeling task is difficult even for skilled surgeons, because ILM is a quite thin film on retina and there is a risk to damage the retina at peeling. In order to obtain the skill of ILM peeling and even evaluate newly developed medical devices, the surgical model that can be used for quantitative evaluation is highly demanded. Therefore, here we propose a surgical model for eye surgery named "Bionic-eye". Fundus of Bionic-eye has artificial ILM and retina. In addition, we assembled Bionic-eye on a whole body surgical model of human named "Bionic-humanoid".

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

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

DOI： 10.1109/mhs.2015.7438271

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

DOI： 10.1109/mhs.2015.7438320

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We present a novel cell manipulation method based on vibration-induced flow in open-chip environment. By applying circular vibration to a chip having micropillar patterns on its surface, local whirling flow is induced around the micropillars. Therefore, by patterning micropillar array on a chip and applying the circular vibration to the chip, we can achieve cell transportation along the array in an open chip environment. We theoretically analyzed this phenomenon with a single micropillar, and experimentally evaluated behaviours of manipulated microbeads with two micropillars. We confirm there are different manipulation modes according to the pitch of micropillars. We designed the micropillar array for an oocyte transportation based on these evaluations. We succeeded in the transportation of oocytes with up to 35.6 mu m/s and confirmed that the velocity can be changed by changing the frequency and amplitude of the applied vibration.

DOI： 10.1109/iros.2015.7353552

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

We proposed novel optically-driven microtool which can control cell adhesion on its surface by laser heating. The microtool is made of polystyrene microbead coated with thermo-responsive hydrogel, Poly (N-isopropylacrylamide) (PNIPAAm). Target cells adhere to the surface of the microtool at the temperature higher than Lower Critical Solution Temperature (LCST) and do not adhere at the temperature lower than LCST. Thus, the microtool can transport target cell by controlling adhesion of the cell on its surface by changing the temperature. The microtool is heated by irradiation of infrared laser used for optical tweezers and the temperature is controlled by regulating laser power and environmental temperature. First, relationship between temperature and cell adhesion rate of PNIPAAm was evaluated. Second, we experimentally measured the controllability of the temperature by temperature-sensitive fluorescent reagent. We confirmed that the temperature of the tool was increased 7.5 degrees C by irradiating the laser. Finally, we demonstrated adhesion and transportation of the single Synechocystis SPP. 6803 by irradiating laser with 65 mW.

DOI： 10.1109/nano.2015.7388730

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

We propose a system that transports oocytes and measures their mechanical characteristics in an open environment using a robot integrated microfluidic chip (chip). The cells are transported through a micropillar array in the chip, and their characteristics are measured by a mechanical probe and a force sensor. Because the chip has an open microchannel, important cells such as oocytes are easily introduced and collected without the risk for losing them. In addition, any bubbles trapped in the chip, which degrade the measurement precision, are easily removed. To transport the oocytes through the open microchannel, we adopt a transportation technique based on a vibration-induced flow. Under this flow, oocytes arrive at the measurement point, where their mechanical characteristics are determined. We demonstrate the introduction, transportation, measurement of mechanical characteristics, and collection of oocytes using this system.

DOI： 10.3390/mi6050648

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We present a novel cell manipulation method using vibration-induced local flow in open chip environment. By applying circular vibration to micropillars on a chip, local whirling flow is induced around the micropillars. From the observation of this unique phenomenon, we propose the concept of cell manipulation in open chip environment. We analyze this phenomenon theoretically, and evaluate the effect of the frequency and the amplitude of applied vibration. We design the micropillar array according to the analysis for transportation for oocytes. We apply the proposed method to transportation of mouse oocytes and confirm that the velocity of transportation is approximately 25 mu m/s.

DOI： 10.1109/memsys.2015.7050921

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We present a cell manipulation method by using vibration induced whirling flow. The local flow is induced just around a micropillar by applying circular vibration to the micropillar. By patterning a micropillar array on a chip and applying circular vibration to the chip, flow for cell transport can be generated along the array. As an application, we demonstrate a single cell extraction using the vibration-induced flow and single cell catcher made by thermo-responsive gel. Target cells are transported to the single cell catcher by vibration induced flow and caught by the single cell catcher. We tried 30 times single cell extraction, succeeded in 100% single cell catch and 60% extraction to external culture well.

DOI： 10.1109/mhs.2014.7006136

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

We propose a single cell extraction chip with an open structure, which utilizes vibration-induced whirling flow and a single cell catcher. By applying a circular vibration to a micropillar array spiral pattern, a whirling flow is induced around the micropillars, and target cells are transported towards the single cell catcher placed at the center of the spiral. The single cell catcher is composed of a single-cell-sized hole pattern of thermo-responsive gel. The gel swells at low temperatures (less than or similar to 32 degrees C) and shrinks at high temperatures (greater than or similar to 32 degrees C), therefore, its volume expansion can be controlled by an integrated microheater. When the microheater is turned on, a single cell is trapped by the hole pattern of the single cell catcher. Then, when the microheater is turned off, the single cell catcher is cooled by the ambient temperature. The gel swells at this temperature, and the hole closes to catch the single cell. The caught cell can then be released into culture wells on a microtiter plate by heating the gel again. We conducted single cell extraction with the proposed chip and achieved a 60% success rate, of which 61% cells yielded live cells.

DOI： 10.3390/mi5030681

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

Here we proposed a novel device named CACS (Convective Accumulation-based Cell Separator) system that is composed of a cell-trapper unit with accessible (open-structured) microfluidic device and a cell-picker device with high aspect ratio PDMS pillars. Utilizing this systematic instrument, we demonstrated proof-of-concept for cell separation through the process of (1) single cell trap in a well (2) single cell picking by pillar-based tweezers and (3) cell recovery. The optimized system for mammalian cells had enabled us to trap-in and pick-up target cells in 100% efficiency as far as tested. Moreover, picked cells showed 74.5% viability, as a result of a less-invasive cell separation technique. Furthermore, a series of different PDMS pillars indicated their varied efficiency in pick-up and recovery steps. We also found out that the aspect ratio of PDMS pillar is critical for tweezing a cell of interest. To improve on the performance of CACS system, further tuning is necessary, especially on the recovery unit for achieving an efficient and damage-free separation. Though CACS system shows low-throughput at this moment, its simplicity is applicable for any cell type by optimizing each pipeline.

DOI： 10.1109/memsys.2014.6765821

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We proposed hybrid nanorobot that can be manipulated by optical tweezers and has hybrid structure integrating functional nanomaterials. We employed femtosecond laser exposure for fabrication of the nanorobot having 3D structure with nanometric size and integrating functional nanomaterials. We succeeded in fabricating nanorobot with carbon nanotubes (CNTs) that has a high photothermal efficiency. We demonstrated single cell puncture with the nanorobot by irradiating infrared (IR) laser to CNT and generating heat on that point. The puncture shape was dependent on irradiated lase power. Furthermore, we evaluated optical manipulation characteristics of the nanorobot.

DOI： 10.1109/mhs.2013.6710426

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Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

Single cell analysis is attracting large attention because that makes possible more quantitative and detailed analysis compared to conventional cell analysis. In this study, we proposed single cell temperature measurement devise by using high thermal conductive nano pillars and temperature sensitive fluorescent reagent. We fabricated the temperature measurement device and performed temperature calibration, finite element analysis and cell incubation on the device.

DOI： 10.1109/mhs.2012.6492500

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC APPLIED PHYSICS  

We report a theoretical study on the electronic structures and photo-assisted transport properties of three types of impurity-doped carbon nanotubes: boron or nitrogen substituted and pyridine-like nitrogen-doped. The pyridine-like nitrogen-doped carbon nanotubes exhibit a nearly flat impurity band between the valence and the conduction bands, whereas the boron- and nitrogen-substituted nanotubes show dispersive impurity bands overlapping the valence and the conduction bands, respectively. Due to the existence of the flat band, the pyridine-like nitrogen-doped carbon nanotubes show unipolar transport and their conductances are enhanced by increasing the power and frequency of the light. (C) 2009 The Japan Society of Applied Physics

DOI： 10.1143/JJAP.48.08JB02

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Event date： 2019.11 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.11 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.11 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.10 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2019.10 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2019.10 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2019.10 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2019.9 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.9 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.9 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.7 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2019.6 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2019.6 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2019.1 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2018.12 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2018.12 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2018.12 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2018.11 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2018.11 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2018.10 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2018.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2018.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2018.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2018.6 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2018.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2017.10 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2017.5 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2017.5 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2017.5 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2017.5 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2017.5 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2017.3 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2017.1 - 　

Language：English   Presentation type：Poster presentation  

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Event date： 2016.12 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2016.11 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2016.11 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2016.11 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2016.11 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2016.11 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2016.10 - 　

Language：English   Presentation type：Oral presentation (general)  

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Event date： 2016.9 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2016.9 - 　

Language：Japanese   Presentation type：Oral presentation (general)  

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Event date： 2016.9 - 　

Language：Japanese   Presentation type：Poster presentation  

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Event date： 2016.6 - 　

Language：Japanese   Presentation type：Poster presentation