Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Institute of Physics  

In this article, we present a proof-of-concept for microfluidic systems with high functional variability using reinforcement learning. By mathematically defining the objective of tasks, we demonstrate that the system can autonomously learn to behave according to its objectives. We applied Q-learning to a peristaltic micropump and showed that two different tasks can be performed on the same platform: adjusting the flow rate of the pump and manipulating the position of the particles. First, we performed typical micropumping with flow rate control. In this task, the system is rewarded according to the deviation between the average flow rate generated by the micropump and the target value. Therefore, the objective of the system is to maintain the target flow rate via an operation of the pump. Next, we demonstrate the micromanipulation of a small object (microbead) on the same platform. The objective was to manipulate the microbead position to the target area, and the system was rewarded for the success of the task. These results confirmed that the system learned to control the flow rate and manipulate the microbead to any randomly chosen target position. In particular, the manipulation technique is a new technology that does not require the use of structures such as wells or weirs. Therefore, this concept not only adds flexibility to the system but also contributes to the development of novel control methods to realize highly versatile microfluidic systems.

DOI： 10.1063/5.0087079

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MYU K.K.  

DOI： 10.18494/sam.2021.3613

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

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

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Institute of Physics  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Institute of Physics  

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

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

Human hepatitis B virus (HBV) infection remains a serious health problem worldwide. However, the mechanism for the maintenance of HBV in a latent state within host cells remains unclear. Here, using single-cell RNA sequencing analysis, we identified four genes linked to the maintenance of HBV in a liver cell line expressing HBV RNA at a low frequency. These genes included DOCK11 and DENND2A, which encode small GTPase regulators. In primary human hepatocytes infected with HBV, knockdown of these two genes decreased the amount of both HBV DNA and covalently closed circular DNA to below the limit of detection. Our findings reveal a role for DOCK11 and DENND2A in the maintenance of HBV.

DOI： 10.1371/journal.pone.0246313

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MYU, SCIENTIFIC PUBLISHING DIVISION  

We report a reflow process for forming rounded channels of submillimeter height. In this method, a hot-melt glue comprising primarily of an ethylene-vinyl acetate (EVA) copolymer is patterned onto a substrate via vacuum-assisted micromolding (VAM) in capillaries using polydimethylsiloxane (PDMS) molds. This method enables a submillimeter channel structure to be fabricated using a thermoplastic resin. Subsequently, by heating the mold, rounded crosssectional channels with a height of 100 mu m order can be fabricated, which is difficult to achieve in the conventional reflow process using positive resists. By observing the cross-sectional shape of the reflowed mold, it is confirmed that the cross-sectional shape of the channels can be controlled by changing the heating time. In addition, the method offers flexibility in terms of the channel layout. As an application to microfluidic devices, we fabricate and evaluate a microperistaltic pump comprising three microvalves using a typical hot plate and a small vacuum pump. In addition, the PDMS mold and fabricated glue mold can be used repeatedly. In general, the proposed process is a simple and inexpensive means of fabricating micropumps and valves that can handle large objects such as cell tissues.

DOI： 10.18494/SAM.2021.3379

Web of Science

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

DOI： 10.1073/pnas.2009634118

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

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry  

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

<p>In this paper, we report on the demonstration of a portable immunoassay system consisting of a small centrifugal microfluidic device driver (bento box) and a centrifugal microfluidic device made of polypropylene and fabricated by injection molding.</p>

DOI： 10.1039/d0ay01459a

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier  

DOI： 10.1016/j.mne.2020.100055

Web of Science

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

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

Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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

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

J-GLOBAL

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

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

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

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Japan Society of Applied Physics  

Development of micromanipulation technology such as atomic force microscopy has allowed us to analyze force interactions at single-molecule level. However, conventional methods have limited throughput of the analysis due to their complicated operations. Here, we propose a novel method to achieve the high-throughput analysis of force interactions between biological molecules using the centrifugal force. This method utilizes a tensile force applied to biomolecule attached to microbeads by rotating a substrate after bonding a plurality of microbeads. In order to conduct the experiment, we developed an antibody-immobilized substrate on which an anti-mouse IgG antibody is immobilized on a glass substrate. Analysis of the binding force was also conducted by introducing analytical methods developed for the specific antigen-antibody reaction and nonspecific adsorption of the beads. We have succeeded in taking force interactions between the bead and the substrate.

DOI： 10.7567/1347-4065/ab1b5e

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

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

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

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

This paper reports on the development of an autonomous centrifugal microfluidic device, which automatically executes an enzyme-linked immunosorbent assay (ELISA) on a steady rotational frequency. The device was designed on the principles of CLOCK (Control of Liquid Operation on Centrifugal hydroKinetics) to achieve autonomous centrifugal microfluidics. These demonstrations confirmed that the device achieves accurate flow control of an automated ELISA with fluctuations of the interval time for implementation of each unit (antigen-antibody reaction, wash and injection of detection substrate) being less than 5%. The most optimal method for the immobilization of primary antibodies was investigated for the developed platform. We compared three methods of antibody immobilization on the developed platform, by using polystyrene microbeads, a polyurethane foam structure, and direct immobilization to the reaction chamber. We chose the use of polyurethane foam as the best immobilization method based on reaction efficiency and the convenient handling of the immobilized antibody on the solid phase. Measurement of human albumin was demonstrated using the developed device, and a calibration curve of human albumin detection was successfully prepared with an overall assay operation time of 18 min. The limit of detection (LOD) was estimated to be 0.516 ng/ml, which is comparable with the LOD of 0.707 ng/ml obtained by the assay on a conventional titer plate assay platform.

DOI： 10.1016/j.snb.2018.01.150

Scopus

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

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

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

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

J-GLOBAL

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

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

We have developed a three-dimensional (3D) Lab-on-a-CD immunosensor based on a competitive/noncompetitive assay for small endocrine disruptors and biomolecules. To improve the sensitivity of the 3D Lab-on-a-CD immunosensor, an immobilizing method of capturing-type antibody on the sensor surface was investigated. The method is based on the introduction of a highly reactive amino group to a P(MMA/CEMA) copolymer surface having chlorine, and utilizing a biotin-streptavidin system. The functionality of the 3D Lab-on-a-CD immunosensor was evaluated by measuring mouse IgG. The detection limit was found to be 3 f g/assay (3 x 10(-12) g/assay). After further modification, the 3D Lab-on-a-CD immunosensor, having some characteristics such as a substrate with highly integrated antibodies, is expected to be applicable for highly sensitive immunoassay.

DOI： 10.1002/ecj.12023

Web of Science

Language：Japanese  

J-GLOBAL

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

Language：Japanese   Publisher：Institute of Electrical Engineers of Japan  

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

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

Single cell transcriptome analysis of a cancer tissue can provide objective assessment of subtype population or the activation of each of various microenvironment component cells. In this study, we applied our newly developed technique of single cell analysis to the myometrial infiltration side (M-side) and the endometrial side (E-side) of a human endometrioid adenocarcinoma with squamous differentiation tissues. We also analyzed spherogenic cultures derived from the same tissue to identify putative regulators of stemness in vivo. Cancer cells in the E-side were highly malignant compared with those in the M-side. Many cells on the E-side were positive for spheroid-specific tumorigenesis-related markers including SOX2. In addition, there were higher numbers of epithelial-to-mesenchymal transition (EMT) cells in the E-side compared with the M-side. This study identified a site containing cells with high malignant potential such as EMT and cancer stem-like cells in cancer tissues. Finally, we demonstrate that established endometrioid adenocarcinoma subtype classifiers were variably expressed across individual cells within a tumor. Thus, such intratumoral heterogeneity may be related to prognostic implications.

DOI： 10.1038/s41598-017-14676-3

Web of Science

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

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

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

Centrifugal microfluidics has been recognized as a promising pumping method in microfluidics because of its simplicity, easiness of automation, and parallel processing. However, the patterning of stripe flow in centrifugal microfluidics is challenging because a fluid is significantly affected by the Coriolis force, which produces an intrinsic secondary flow. This paper reports a technical and design strategy for centrifugal microfluidics called "density-gradient-assisted centrifugal microfluidics." The flow behavior is observed with the presence of a density gradient and without a density gradient in two concentrically traveling phase flows. As a result, clear stripe flow pattern is observed with a density difference of 0.05 g/cm(3) between water and a percoll solution at a flow rate of 11.8 mu l/s (7 ml/10 min) and spinning speed of 3000 rpm. In contrast, without a density gradient, it is necessary to reduce the flow rate and spinning speed to 0.1 mu l/s and 1000 rpm, respectively. This paper also presents the use of a density gradient to assist in focusing resin (polystyrene) particles on the boundary of a stripe flow pattern that consists of water and percoll with different densities. Moreover, the density-based separation and sorting of particles in a mixed particle suspension is demonstrated. Polystyrene is selectively focused on the boundary, but silica particles are separated from the focused trajectory due to a difference in density. The separated particles are continuously sorted into different reservoirs with polystyrene and silica separation efficiencies of 96.5% and 98.5%, respectively. The pumping, stripe flow pattern formation, particle concentration, and sorting are simultaneously realized by applying a density gradient and centrifugal force. Therefore, this principle can realize a very simple technique for label-free particle separation by just spinning a disk device and can be applied in other applications by the use of the density-gradient assistance.

DOI： 10.1007/s10544-017-0158-3

Web of Science

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

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

This study demonstrates a novel autonomous flow-control technique using siphon-shaped microchannels on a steadily rotating centrifugal microfluidic device. We also develop a simple microfluidic device, which comprises simple casted polydimethylsiloxane, capable of implementing a multistep, timely flow injection, and the replacement of the liquid present in a chamber, without requiring external triggers to switch the flow operation modes. We demonstrate the multistep, timely flow injection system with the steadily rotating, disk-shaped, microfluidic device and the four steps of flow injection. We investigate the effect of surface tension, which affects the liquid replacement error, on the extent of the remaining liquid plug in a siphon-shaped microchannel to realize a stable liquid replacement. We also investigate the liquid behavior in the siphon-shaped microchannels and develop a suitable design to realize autonomous liquid replacement in the reaction chamber, which is required in automatic chemical processes. Moreover, we develop a device capable of implementing the three-step liquid injection process and the liquid replacement in a liquid reservoir, which are potentially applied with a chemical analysis process, such as the enzyme-linked immunosorbent assay.

DOI： 10.1039/c7ra03721j

Web of Science

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

We have developed a 3D Lab-on-a-CD immunosensor based on a competitive/non-competitive assay for small endocrine disruptors and biomolecules. To improve the sensitivity of the 3D Lab-on-a-CD immunosensor, an immobilizing method of capturing-type antibody on the sensor surface was investigated. The method is based on the introduction of a highly reactive amino group to a P(MMA/CEMA) copolymer surface having chlorine, and utilizing a biotin-streptavidin system. The functionality of the 3D Lab-on-a-CD immunosensor was evaluated by measuring mouse IgG. The detection limit was found to be 3 f g/assay (3×10-12 g/assay). After further modification, the 3D Lab-on-a-CD immunosensor, having some characteristics such as a substrate with highly integrated antibodies, is expected to be applicable for highly sensitive immunoassay.

DOI： 10.1541/ieejeiss.137.418

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：MYU, SCIENTIFIC PUBLISHING DIVISION  

In this paper, we present the demonstration of a size-encoded bead-based multiplexed immunoassay with image cytometric decoding and readout. Antibodies were immobilized on polystyrene microspheres by physical adsorption and employed for the demonstration of this duplexed immunoassay. First, we carried out a duplexed immunoassay with a mouse and rat IgG detection system and discussed the problem of cross-reactivity inherent to these immunoreaction systems. We then carried out a duplexed immunoassay with a mouse IgG and human albumin detection system, which was less cross-reactive. We subsequently demonstrated the application of size-encoded image cytometric decoding and the detection of mouse IgG and human albumin using this duplexed immunoassay system.

DOI： 10.18494/SAM.2017.1559

Web of Science

Language：Japanese   Publisher：Institute of Electrical Engineers of Japan  

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

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Institute of Physics  

This paper presents strategies that attempt to solve two key problems facing the commercialization of microfluidics: cost reduction in microfluidic chip manufacturing and microfluidic device driver development. To reduce the cost of microfluidic chip manufacturing, we propose to use of three-dimensional (3D) printers for direct digital manufacturing (DDM). An evaluation of 3D micro-scale structure printing using several 3D printers is reported, and some of the technical issues to be addressed in the future are suggested. To evaluate micro-scale printing, three types of 3D printers, with the ability to print structures on the scale of several hundred meters, were selected by first screening six 3D printers. Line and space patterns with line widths of 100–500 µm and an aspect ratio of one were printed and evaluated. The estimated critical dimension was around 200 µm. The manufacturing of a monolithic microfluidic chip with embedded channels was also demonstrated. Monolithic microfluidic chips with embedded microchannels having 500 × 500 and 250 × 250 µm²cross sections and 2–20 mm lengths were printed, and the fidelity of the channel shape, residual supporting material, and flow of liquid water were evaluated. The liquid flow evaluation showed that liquid water could flow through all of the microchannels with the 500 × 500 µm²cross section, whereas this was not possible through some of the channels with the 250 × 250 µm²cross section because of the residual resin or supporting material. To reduce the device-driver cost, we propose to use of the centrifugal microfluidic concept. An autonomous microfluidic device that could implement sequential flow control under a steadily rotating condition was printed. Four-step flow injection under a steadily rotating condition at 1500 rpm was successfully demonstrated without any external triggering such as changing the rotational speed.

DOI： 10.7567/JJAP.55.06GN02

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

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

We developed a process for micromachining polytetrafluoroethylene (PTFE): anisotropic pyrochemical microetching induced by synchrotron X-ray irradiation. X-ray irradiation was performed at room temperature. Upon heating, the irradiated PTFE substrates exhibited high-precision features. Both the X-ray diffraction peak and Raman signal from the irradiated areas of the substrate decreased with increasing irradiation dose. The etching mechanism is speculated as follows: X-ray irradiation caused chain scission, which decreased the number-average degree of polymerization. The melting temperature of irradiated PTFE decreased as the polymer chain length decreased, enabling the treated regions to melt at a lower temperature. The anisotropic pyrochemical etching process enabled the fabrication of PTFE microstructures with higher precision than simultaneously heating and irradiating the sample. (C) 2016 AIP Publishing LLC.

DOI： 10.1063/1.4941668

Web of Science

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

This study reports the first demonstration of an enzyme-linked immunosorbent assay (ELISA) using a microfluidic device that was fabricated in a three-dimensional (3D) printer. The centrifugal microfluidic device is driven by a mini-centrifuge realized fluidic control for the ELISA, including the injection of a reagent, incubation and reaction, and washing and draining of the reagent, by simply applying the reagent and spinning the device. The analysis of the reaction was accomplished by smartphone-based colorimetric measurements using a free application, and the results suggest that the microfluidic device followed by the use of the smartphone application showed a detection limit (0.89 ng ml-1) that was comparable with conventional absorbance measurements (0.96 ng ml-1) using a plate reader. Therefore, our results suggest that widely available equipment, such as mini-centrifuges, smartphones, and, in the near future, 3D printers, can potentially contribute to the commercialization of the microfluidic immunoassay system.

DOI： 10.1039/c5ay01969a

Scopus

Language：Japanese  

J-GLOBAL

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

© 2015 Elsevier B.V. Liquid electrode plasma (LEP) optical emission spectrometry (OES) is a novel elemental analysis method that utilizes discharged microplasma in a liquid sample as an excitation source to detect metal ions. LEP-OES has been commercialized as a handy device that uses disposable microfluidic chips. To improve the sensitivity, integration of a solid phase extraction (SPE) column into the LEP chip as preconcentrator was proposed with the use of an external syringe pump for fluid actuation. However, poor control of the external pump at low pumping volumes and high back-pressures caused poor analytical performance of the integrated system. In this study, a simply designed internal pneumatic injection pump was redeveloped and employed as a fluid actuator. The internal pump can be easily operated by an automated pneumatic pressure controller and is capable of injecting a reproducible amount of eluent for each measurement cycle of SPE-LEP. Additionally, the pump acted as a valve to stop the backflow caused by the high pressure created by plasma generation. More precise flow control by the internal pump helped improve the precision of the measurements. For data processing, exponentially modified Gaussian model was utilized to describe the elution peaks. The limit of detection for lead (0.4. ng/mL) was 50 times improved in comparison with conventional LEP. The proposed method and data processing model can be used to develop on-chip detection applications for methods that utilize pulsed microplasma sources.

DOI： 10.1016/j.snb.2015.07.117

Scopus

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

In this paper, we report the demonstration of a flow sequencing method in a centrifugal microfluidic device rotated at a constant speed. The simple poly-dimethylsioxiane chip, which consists of microchannels, chambers, and vent holes, was integrated in a compact disk substrate, and multistep flow sequencing was executed by simply spinning the device at a constant rotational speed. All the triggers were controlled by a water clock using the liquid meniscus as the clock hand. The flow modes to the sample chambers were switched by switching the air supply to the sample chambers, depending of on whether the meniscus water clock was inside the channel connection (disabling air supply) or outside it (enabling air supply). A four-step flow sequence was successfully executed using two different connections of the chambers, namely, parallel connection and serial connection. Highly reproducible autonomous trigger timing with a typical error of less than 3% was achieved. Delicate adjustment of the flow sequencing by varying the channel geometry was also demonstrated. The time-scaling of the flow sequencing was accomplished by changing the viscosity of the fluid in the water clock. Additionally, a four-step flow sequencing involving a flow injection chain was successfully demonstrated by serial connection. Through combinations and further variations of these concepts, it is expected that the proposed method would be used to realize higher-order flow programs in steadily spinning centrifugal microfluidic devices.

DOI： 10.1016/j.snb.2015.05.051

Web of Science

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：M Y U Scientific Publishing Division  

In this paper, we report on the development of a mini-centrifuge-compatible microfluidic device that implements multistep liquid handling to realize bioassay protocols including enzymatic amplification steps such as enzyme-linked immunosorbent assay (ELISA). A device was developed by considering the geometry of the fluidic channel, the wettability of the microchannel, the volume and position of the chambers, and the entire assay process. The assay process includes injection of the sample into the reaction chamber, washing of the chamber, injection of the substrate, and injection of the stop buffer by two-mode (spin and stop) control that can be accomplished with an affordable minicentrifuge. During the assay protocol, both injection of the liquid into a chamber and draining of the liquid from the chamber are realized at a constant rotational speed, which is a key function for enzymatic amplification using a siphon-shaped channel. The injected liquid is held in the reaction chamber, both in the presence and absence of centrifugal force, then the liquid is drained once a liquid exceeding the critical volume is injected into the chamber. The reaction chamber was prepared for enzymatic amplification. The device was then applied to assay the avidin-biotin system, and the resulting assay performance was demonstrated to be comparable to or better than the conventional titer plate assay performance.

DOI： 10.18494/SAM.2015.1078

Scopus

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

Compared to the conventional silicon-based technology, the solution process appears to be a revolution in the field of micro/nanofabrication due to its advantages of high efficiency in material and energy consumption and the use of low cost material. In this paper, we introduce a new approach to fabricate BioMEMS devices using this novel technology to make microcavity. Zirconium oxide patterns were formed on the silicon substrate simply by spin coating its precursor and thermal imprinting technique. We used poly-propylene carbonate (PPC) for the sacrificial material due to its unique pyrolysis property. The PPC was coated on the ZrO patterns and excess film was etched by oxygen plasma but retaining PPC structure between the lines of ZrO pattern. Then another ZrO layer was coated to encapsulate the PPC. The final microcavity structures were obtained by just baking the substrate by pyrolyzing the PPC. The obtained results show the approach's prospect of becoming an ideal alternative for the current BioMEMS micro/nanofabrication technologies

DOI： 10.1088/2043-6262/5/3/035003

Web of Science

Other Link： http://orcid.org/0000-0001-5329-7387

Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society  

An on-chip pulse-heating ionization source for protein samples was developed for the realization of miniaturized mass spectrometry. A protein analyte was ionized on a chip by applying only thermal energy to the solid phase sample without a laser, high voltage, or heated ambient gases. A fabricated ionization source consisting of a Pt/Cr microheater (width: 30 μm
length: 100 μm) on a silicon substrate was coupled with a time-of-flight mass filter to analyze a protein sample of bovine serum albumin (BSA, M = 66 kDa). A singly charged BSA ion and other multiply charged BSA ions were generated in the presence of 2,5-dihydroxybenzoic acid as a matrix. To detect the singly charged BSA ion, the required surface energy density of 1.65 × 10-2 μJ/μm2 was applied to the microheater for 500 ns. The use of the 2,5-dihydroxyacetophenone matrix resulted in the generation of the multiply charged protein analyte, while the use of the sinapic acid matrix showed abundant peaks in the low m/z region. © 2014 American Chemical Society.

DOI： 10.1021/ac501407c

Scopus

Language：English  

Language：English  

Language：English  

Language：Japanese  

Language：Japanese  

Language：English  

Language：Japanese  

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

A miniaturized solid-phase peptide synthesis (SPPS) system was developed aiming a novel concept of programmable biosensor that can flexibly change the target on-site and on-demand. Oligopeptides, utilized as probes for the biosensor, were synthesized by the on-chip SPPS on a single bead trapped at the center of a micro channel. After the completion of probe synthesis, a sample solution containing target was exposed to the beads. The selective bindings of targets and the synthesized oligopeptide probes were optically measured. As examples of sensing, YOYO1 label DNA binding with three probe sequences RHKS, EDED (hydrophilic), LAGV (hydrophobic), and also Ni binding with His-tag were investigated. Sequence-dependent different affinity and selectively bindings of these targets were confirmed. These results demonstrated the concept of a programmable biosensor. © 2013 Elsevier B.V.

DOI： 10.1016/j.snb.2013.10.086

Scopus

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

This paper reports the development of fully automated miniaturized immunoassay system. The system consist of postage stamp sized microchip and compact (post card sized foot print) microchip driver. To realize easy sample loading into the microchip, surface modification of polydimethylsiloxane (PDMS) was developed, and life time of the modified surface up to 9 days is confirmed. The microchip just consumes a droplet of blood (2 μl) and the loading and metering of the sample is realized by capillary action, therefore the microchip is compatible with blood collection method by using lancet needle. Fully automated immunoassay protocol in the system is demonstrated within 15 min using whole blood sample. Finally, fully automated detection of antigen (insulin) was successfully demonstrated in the developed system. © 2013 Springer-Verlag Berlin Heidelberg.

DOI： 10.1007/s00542-013-1772-5

Scopus

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

Fluorescence microscopy has been greatly contributed to the development of new science and technology in the field of microfluidics. In the case of centrifugal microfluidics, a microscale fluidic system is constructed on a spinning disk-shaped substrate
however, while microscopic stroboscopes have been developed, fluorescence imaging has not yet been demonstrated. This paper reports on the development of the first imaging technique that can observe small (micrometer) fluorescent objects on a spinning fluidic system. This technology is based on the combination of a Xe bulb strobe, a coaxial optics microscope, and a fluorescent optical filter. The observation of small particles on a spinning disk was demonstrated at both the bright field setting and the fluorescence setting. The system successfully demonstrates the observation of fluorescence particles on a spinning disk (at 3,000 rpm) and the sedimentation of particles in a suspension flow.

DOI： 10.1007/s10404-014-1426-7

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Japan Society of Applied Physics  

This paper reports the application of liquid electrode plasma atomic emission spectrometry (LEP AES) integrated with on-chip solid phase extraction (SPE) for determination of lead (Pb). LEP AES is a novel elemental analysis method employing micro-plasma in the sample solution as excitation source. The integration of SPE to LEP chip shows high potential of application with several merits because on-chip SPE enables the effective use of sample. In the work an improved LEP chip integrated with SPE was developed for trace lead detection. Chip design and pulse voltage were proposed to eliminate the ash generation and minimize the channel expansion. Some analytical parameters were optimized. With sample volume of 1 mL calibration curve in the range of 0-100ng/mL the correlation coefficient of 0.992 and limit of detection (LOD) of 0.64ng/mL were obtained. With the support of SPE, LOD was improved about 30 times. © 2014 The Japan Society of Applied Physics.

DOI： 10.7567/JJAP.53.05FS01

Scopus

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Japan Society of Applied Physics  

Due to constant outbreak of deadly microbial pathogens and threats of bio-warfare or -terrorism, developing of novel diagnostic device is highly necessary. In spite of the high selectivity, high accuracy and high sensitivity of conventional biosensors, they could not meet the situations that require the changing of analytical target. Thus programmable biosensor is proposed here to flexibly change the target analyte by changing sensing probe molecule on-site and on-demand. We propose to synthesize short peptide as probe molecule on-chip following traditional Fmoc-solid phase peptide synthesis strategy. Linear hepta-peptide probe (-NH-PPGQPHH-NH2) is synthesised on-chip (optimized conditions of 15min coupling time and 5μl/min of flow rate) and successfully performed in situ detection of the target biomolecule (streptavidin) on the same microchip. © 2014 The Japan Society of Applied Physics.

DOI： 10.7567/JJAP.53.05FA09

Scopus

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

This paper reports a fundamental study of the stripe laminar flow pattern on a centrifugal microfluidic device with the goal of realizing a sedimentation-based, continuous mode particle separation technique. Microfluidic channels were designed with a concentrically integrated microchannel, and the patterning of the flow in the channel was investigated. A significant secondary flow was observed as a preliminary result. We conclude that the origin of this secondary flow was not the Dean force, because it was observed in a straight microchannel, but was not observed in curved channel during the spinning of the system at rest. The transition of the pattern was investigated using a simulation and experiment, and the flow pattern's dependence on the rotational speed was determined, which suggested that the origin of the secondary flow was the Coriolis force. The significance of the secondary flow was controlled by adjusting the rotational speed of the disk, and the flow rate and laminar flow patterns were controlled by the stripe flow pattern. © Springer-Verlag Berlin Heidelberg 2013.

DOI： 10.1007/s10404-013-1194-9

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER ADVANCED TECHNOLOGY  

A new sensitive gold-linked electrochemical immunoassay (GLEIA) for the detection of the pregnancy marker human chorionic gonadotropin (hCG) has been developed using the direct electrochemical detection of Au nanoparticles. We utilized single-walled carbon nanotube (SWCNT) microelectrodes; 24 SWCNT microelectrodes were arrayed on a single Si substrate 25 x 30 mm(2) in size, for the development of a new GLEIA (SWCNT-GLEIA). This SWCNT-GLEIA provided convenient and cost-effective tests with the required antibody and antigen sample volumes as small as 2.0 mu L for a group of 4 SWCNT microelectrodes. In addition, this assay also exhibited properties of high sensitivity and selectivity benefitting from the intrinsic extraordinary features of SWCNTs. Using scanning electron microscopy, we also observed Au nanoparticle-labeled antigen-antibody complexes immobilized on the surface of the SWCNT microelectrodes. The concentration of the pregnancy marker (hCG) showed a linear relationship with the current intensity obtained from differential pulse voltammetry measurements with a limit of detection (LOD) of 2.4 pg/mL (0.024 mIU/mL) hCG. This LOD is 15 times more sensitive than a previous GLEIA, which used screen-printed carbon electrodes. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bios.2012.11.017

Web of Science

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

To the best of our knowledge, this is the first report on paper-based devices for automating the sequential multistep procedures of a sandwich-type enzyme-linked immunosorbent assay (ELISA) that require only a single-step application of the sample solution. The device was based on a piece of nitrocellulose (NC) membrane with specially designed channels, where all the reagents are applied at different locations in order to control the fluid travel to the detection region. The inkjet printing method, a simple and low-cost process, was used to create the flow channel and device barrier patterns. The fabricated barrier was found to be an efficient boundary for the liquid along the printed design in the NC membrane, enabling direct control of the reagent flow time. ELISA results were obtained with a single-step sample application. The developed devices (so-called automated paper-based devices) provided a simple procedure for the sandwich ELISA, while reducing assay time and reagent consumption. Colorimetric results were measured using digital camera imaging with software processing. The capability of the method developed herein was successfully used to determine the levels of human chorionic gonadotropin (hCG) by ELISA. © The Royal Society of Chemistry.

DOI： 10.1039/c2lc40690j

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

Liquid electrode plasma - Atomic emission spectrometry (LEP-AES) is a novel elemental analysis method where a liquid sample is filled in a micro channel that has a narrow part at the center. High voltage is applied to the solution at the both ends of the channel, and consequently microplasma is generated in the channel. The microplasma is an excitation source for atomic emission spectrometry. The method is suitable for heavy metal detection. In this work, to improve detection limit, we integrated a solid phase extraction (SPE) column on a liquid electrode plasma chip (LEP chip) to improve the sensitivity of this method for lead (Pb) detection. The chip design and flow control technique was proposed based on the point of reducing the necessary eluent for one measurement. Chip pattern was made by Polydimethylsiloxane (PDMS) employing negative photolithography. The integrated chip was successful in detecting 10 ppb Pb in solution. Detection limit for Pb of LEP method is improved. © 2013 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.mee.2013.02.086

Scopus

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

In this paper we report the improvement of sensitivity for liquid electrode plasma atomic emission spectrometry (LEP- AES) by combination with solid phase extraction (SPE) and constant volume pneumatic membrane micropump. The micropump can provide a steady volume of liquid for elution process of SPE, enabling us to reduce eluent more reliably and/or to use the analyte more effectively. The chip can detect Pb of 10 ng (1 ppb with 10 mL sample and 10 ppb with 1 mL sample). Copyright © (2013) by the Chemical and Biological Microsystems Society All rights reserved.

Scopus

Language：English   Publishing type：Research paper (scientific journal)   Publisher：The Institute of Electrical Engineers of Japan  

With the aim of developing compact and sensitive immunoassay devices for point-of-care testing, we studied an electrochemical method by using continuous flow in a microchannel gold-linked electrochemical immunoassay (GLEIA) on a screen-printed carbon electrode. Conventional GLEIA is a useful method to detect low-level antigen in real samples, but it requires a long incubation time (∼1h) and milliliter-order reagent volumes for measurement. In this study, a screen-printed electrode was put into a microfluidic channel to study the microchannel effect on GLEIA. By limiting the diffusion volume during the pre-oxidation to oxidation step of GLEIA, we found that the sensitivity increased. Owing to the continuous flow in a microchannel, the antigen-antibody reaction was accelerated, resulting in a 10 min detection time. It was also effective in reducing the minimum volume of washing buffer required.

DOI： 10.1541/ieejsmas.133.344

CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JALC/10026198759?from=CiNii

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE SA  

A stacked-type centrifugal microfluidic device with three-dimensional (3D) microchannel networks and multifunctional capillary bundle structures is developed, and an immunoassay for the detection of immunoglobulin G (IgG) is demonstrated. The device consists of multiple layers of disk-like chips with conventional planar microchannels and vertical capillary bundle structures that are constructed on disks of poly(dimethylsiloxane) and poly(methyl methacrylate). The integration of multiple reactors up to 10 reactors on a disk with 8cm in diameter is realized by reducing the area of reservoir but increasing the thickness. Moreover the thick optical detection reservoir is also realized for absorption spectroscopy in the 3D centrifugal microfluidics. 3D liquid valving on the vertical capillary bundle structures and liquid transportation through these structures are successfully demonstrated. The results show the successful control of the multistep liquid injection without problems such as blockage of capillary bundle by bubbles that expected to be caused due to 3D structure. The results of the immunoassay show clear response to analyte concentration suggesting successful unit operations in developed 3D centrifugal microfluidic device for immunoassay. Finally, the advantages and impact of the 3D design for the development of high-performance centrifugal microfluidic systems are summarized. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.snb.2012.03.028

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE SA  

In this paper, we developed on-chip vacuum generation technique using gas-liquid phase transition. Fabricated quartz chip was composed simply of a structural vacuum chamber and a diaphragm for pressure measurement by laser displacement meter. Efficient reduction of pressure in the chamber was accomplished by the phase transition with the simple design of the fabricated chip. The pressure was reduced by decreasing the temperature of low boiling point liquid filled into the chamber after closing its valve. The lowest pressure attained to 50.8 kPa (diethyl ether) or 23.2 kPa (water) at 7 min from atmospheric pressure by using diethyl ether and water, respectively. The highest performance of micro vacuum pump was achieved. The absolute pressure below 25 kPa was maintained about 20 min due to low leakage of the fabricated chip. (C) 2011 Elsevier B.V.All rights reserved.

DOI： 10.1016/j.sna.2011.12.003

Web of Science

Other Link： http://orcid.org/0000-0001-5329-7387

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

In this paper, we describe two simple different ways to fabricate an array of single-walled carbon nanotubes (SWCNT) microelectrodes from SWCNT network, grown on Si substrate, through micro-fabrication process. Two kinds of material, photoresist - organic compound and sputtered SiO2, were used as an insulator layer for these arrays of SWCNT microelectrodes. The SWCNT microelectrodes were characterized by scanning electron microscopy (SEM), Raman spectroscopy, and electrochemical measurements. The SWCNT microelectrodes with sputtered SiO2 as an insulator exhibit some prior advances to these used photoresist layer as insulator such as much stable in harsh condition (high active organic solvents) and high current density (24.94 mu A mm(-2) compared to 2.69 mu A mm(-2), respectively). In addition, the well-defined geometry of SWCNT microelectrodes is not only useful for investigating kinetics of electron transfer, but also promising candidate in electrochemical sensors application. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.talanta.2012.01.023

Web of Science

Other Link： http://orcid.org/0000-0001-5329-7387

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

We report the use of liquid electrode plasma-atomic emission spectrometry (LEP-AES) in protein sensing studies employing Ag nanoparticle labeling. LEP-AES requires no plasma gas and no high-power source and is suitable for onsite portable analysis. Human chorionic gonadotropin (hCG) was used as a model target protein, and the immunoreaction in which hCG is sandwiched between two antibodies, one of which is immobilized on the microwell and the second is labeled with Ag nanoparticles, was performed. Sensing occurs at the narrow pass in the center of a quartz chip following oxidative dissolution of the Ag nanoparticles by nitric acid. hCG was analyzed in the range from 10 pg/mL to 1 ng/mL, and the detection limit for hCG was estimated at 1.3 pg/mL (22.8 fM). The proposed detection method has a wide variety of promising applications in metal-nanoparticle-labeled biomolecule detection. © 2011 American Chemical Society.

DOI： 10.1021/ac202782b

Scopus

PubMed

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

This paper describes the development of a highly sensitive liquid-electrode plasma atomic emission spectrometry (LEP-AES) by combination of quartz glass chip and sample flow system. LEP-AES is an ultracompact elemental analysis method, in which the electroconductive sample solution is put into a microfluidic channel whose center is made narrower (similar to 100 mu m in width). When high voltage pulses (1500 V) are applied at both ends of the channel, the sample evaporates locally at the narrow part and generates plasma. By the emission from the plasma, elemental concentration is analyzed In this paper, the limits of detection (LODs) were investigated in various conditions of accumulation time, material of the chip, and the sample flow. It was found that the long accumulation using the quartz chip with sample flow was effective to improve LOD. Authors suggested that this was because bubbles remaining after each plasma pulse were removed from the narrow channel by sample flow, resulting in highly reproducible plasma generation, to enable a high accumulation effect. Finally, LODs were calculated from a calibration curve, to be 0.52 mu g/L for Cd and 19.0 mu g/L for Pb at optimized condition. Sub-ppb level LOD was achieved for Cd.

DOI： 10.1021/ac2020646

Web of Science

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

In this work, a sensitive label-free impedimetric hCG-immunosensor was constructed by using a commercial screen-printing carbon ink electrode (namely disposable electrochemical printed chip) as the basis. The carbon ink electrode of DEP chip is modified first by deposition of polypyrrole-pyrole-2-carboxylic acid copolymer and thence hCG antibody immobilization via the COOH groups of pyrrole-2-carboxylic acid, which can serve as a linker for covalent biomolecular immobilization. The experimental results exposed that the designed immunosensor is more sensitive than other previously reported immunosensors, in the case of detection limit and linear range for antigen detection. With optimal fabrication parameters, the detection limit for α-hCG was 2.3 pg/mL in 10 mM phosphate buffer saline (PBS) solution containing 1% bovine serum albumine (BSA). Moreover, the use of inexpensive DEP chip as a basis for these immunosensors will allow for simple instrumentation, disposable and portable at low cost. This work also demonstrates a new approach to develop a sensitive and label-free impedimetric immunosensor based on screen-printed electrode for applications in clinical diagnosis. © 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.talanta.2011.08.018

Scopus

PubMed

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

A novel micromixer was proposed, fabricated and verified. The new concept of the micromixer is to cross-link many capillaries in a three-dimensional structure. The characteristic flow behaviors were simulated by using the "FLUENT" computational fluid dynamics (CFD) software. The results of the CFD showed unique mixing behavior in three-dimensionally cross-linked capillaries. The mixing performance of the micromixer is strongly influenced by controlling the three-dimensional crossing conditions. The micromixer was fabricated by deep X-ray lithography with multistep exposure. The cross-linked capillary structures were successfully fabricated while controlling the cross-link conditions. The performance of the micromixer was evaluated by using an enzyme reaction. By comparing the mixtures produced with a cross-linked fluid filter and with a fluid filter without cross-linked capillaries, we found that the reaction was accelerated by using the new micromixer. © 2011 Wiley Periodicals, Inc.

DOI： 10.1002/eej.21157

Scopus

Language：English   Publisher：OMICS Publishing  

DOI： 10.4172/2155-6210.1000107

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

A novel recognition element, made of electroactive glycopolymer-modified gold nanoparticles (GM-GNPs), was synthesized and used in an electrochemical assay of saccharide-protein interactions for the detection of concanavalin A (Con A). The electroactivity of the mannose-based GM-GNPs was investigated, and an electrochemical Con A assay system with a disposable screen printed carbon strips was proposed. A complex containing GM-GNPs was formed by a recognition reaction between the mannose-based glycopolymer and Con A. The complex was detected by the pre-oxidation of the GNPs and following reduction scans using differential pulse voltammetry (DPV). Under optimal conditions, a linear relationship between the DPV peak current intensity and Con A concentration was shown within an analytical range of 10-10,000 ng/mL. Our proposed new electric approach provides an interesting tool for the analysis of saccharide-protein interactions. (C) 2011 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.elecom.2011.05.014

Web of Science

Other Link： http://orcid.org/0000-0001-5329-7387

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

This paper describes the first demonstration of DNA trapping in a stacked three-dimensional (3D) microchannel. To carry out the 3D trapping of DNA by using electric force and hydrodrag force, a 3D microchip with a stacked structure is fabricated by the conventional rapid prototyping process and SU-8 peel-off process. Experimental results show that DNA trapping is observed on the application of electric potential with continuous pumping of DNA, but it is not observed in the absence of an electric potential. Further, the results suggest that the trapping throughput of DNA clearly depends on the capillary diameter but not on the flow rate. Thus, we conclude that, for a constant trapping area, reduction in the size of capillary structures with a high density results in an increase in the efficiency of DNA trapping. © 2011 The Japan Society of Applied Physics.

DOI： 10.1143/JJAP.50.06GL13

Scopus

Language：English  

This paper presents high-sensitivity detection of poly-chrolinatedbiphnenil in three-dimensional lab-on-a-CD, which consist of multiple disks with three-dimensional microchannel networks. To perform the automatic sequencing of competitive protocol, capillary barrier type passive valves with vertically embedded capillary valve is designed and fabricated. Even it has three dimensional microchannel network, the performance and reliability of the device for the automatic liquid sequencing is indeed good. Finally we successfully demonstrated the detection of poly-chrolinatedbiphenil. It is notable that the reproducibility of the detection is strongly depending on the quality of scaffold and it is suggested that detection with concentration of sample down to 0.01ng/ml is possible.

Scopus

Language：English  

This paper reports a new type of lab-on-a-CD device with three-dimensional microchannel networks and vertical capillary bundle structures. The device consist of the multiple lab-on-a-CD chips with conventional planer microchannels and vertical microchannels which constructred on the disks made of poly-dimethylsiloxane (PDMS) and poly-methylmethacrilrate (PMMA). Three dimensioanl liquid transportation through vertical capillary bundle structure is suggested by computational fluid dynamics and it is successfully demonstrated by using fabricated chips. Detection of im-munogroblin G(IgG) from mouse is successfully demonstarated in the three-dimensional devices and it is notable that the result suggests quite high-sensitive implying detection limit down to few ng/ml by primitive result.

Scopus

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

This paper reports the first application of poly-tetrafluoroethylene (PTFE) microstructure, which fabricated by synchrotron radiation induced photo-evaporation process, to enzyme-linked immunosorbent assay. The advantages of PTFE microstructure for the development of lab-on-a-chip due to the extremely high-aspect ratio microstructure and chemical stability of PTFE is discussed. The results of immunoassay shows the successful detection of analyte (mouse IgG) with detection range with 0-100 ng/ml. This result suggests the successful immobilization of antibody (anti-mouse IgG goat antibody) onto the X-ray exposed surface of PTFE microstructure and successful demonstration of antigen-antibody reaction in the PTFE microstructure. We also demonstrated the detection of polychlorinated biphenyl (PCB). As the result of demonstration, we successfully detected PCB with ranging analyte concentration of 0.1-10 ng/ml.

DOI： 10.1007/s00542-010-1063-3

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCRIPTA TECHNICA-JOHN WILEY & SONS  

Micro reactors and micro total analysis systems (mu TAS) are recognized as powerful tools for genomics, proteonomics, clinical diagnostics, and environmental testing. In this paper, we describe an enzyme-linked immunosorbent assay (ELISA) using a new micro reactor with a vertical fluid flow operation. This micro reactor is composed of two reaction vessels stacked along the vertical through PMMA fluid filters (circle divide 3 mm). The fluid filters, constructed by deep X-ray lithography, have 2100 pores (circle divide 40 mu m), and possess valve functions, making it possible to maintain the liquid layers in each reaction vessel. In addition, the liquid can be selectively transferred by air pressure from the upper vessel to the lower, and vice versa. As a model of ELISA using the micro reactor, we undertook to detect mouse immunoglobulin (IgG). We bound goat anti-IgG antibody to the surface of the PMMA filters and assayed the IgG by ELISA using an anti-IgG antibody/peroxidase conjugate. We found that the mouse IgG (100 ng/ml) was quantitatively detected within 45 minutes of the analytical period, or about one-third of the period required for the conventional method using micro titer plates. (C) 2010 Wiley Periodicals, Inc. Electron Comm Jpn, 93(4): 50-57, 2010; Published online in Wiley Inter Science (www.interscience.wiley.com). DOI 10.1002/ecj.10137

DOI： 10.1002/ecj.10137

Web of Science

Language：Japanese   Publisher：The Institute of Electrical Engineers of Japan  

The use of three-dimensional (3D) microstructures is becoming essential attempt to develop next generations' microdevices, to integrate many modules and various functions, and enhance the performance of device. In this paper, we present a new concept for lab on a chip using 3D structure and centrifugal force for high-throughput screening system, which has stacked multiple structures with 3D-interconnection.

DOI： 10.1541/ieejeiss.130.1811

CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JALC/00356625681?from=CiNii

Language：Japanese  

CiNii Books

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

We succeeded in making a Si stencil mask for deep X-ray lithography (DXL) by using MEMS fabrication technologies. In order to make this mask, a 200 mu m thick Si wafer was etched through its entire thickness where the remaining silicon served as the absorber for the mask. The minimum line width on the mask was 20 mu m. DXL experiments were executed by using this Si stencil mask on the beamline BL2 at the NewSUBARU SR facility of the Laboratory of Advanced Science and Technology for Industry, University of Hyogo. In our experiment we succeeded in the X-ray exposure of PMMA sheets through their entire thicknesses of 0.5 and 1 mm. This means a success in line/space patterning with 20 mu m line width that can lead to the fabrication of PMMA structure of maximum aspect ratio of 50. Moreover, the sticking was prevented by substituting water with hydrofluoroether employed for after-develop wash operation This Si stencil mask enabled a transcript of more precise pattern using the beamline BL2 at the NewSUBARU SR facility as compared with results from a stainless stencil mask and an Au/polyimide mask.

DOI： 10.1007/s00542-007-0513-z

Web of Science

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

Microfluid filters were fabricated, which possessed 2,100 cylindrical through-bores (psi 40 microm) in 200 microm-thickness polymethylmethacrylate (PMMA) sheets (psi 3 mm), by deep X-ray lithography using synchrotron radiation. To evaluate the microfluid filters as a device for an immunoassay, we bound the goat anti-mouse immunoglobulin G (IgG) antibody to the surface of the filters, and set the filters between reaction vessels stacked vertically in a microreactor. An enzyme-linked immunosorbent assay (ELISA) of mouse IgG using the goat anti-mouse IgG/horseradish-peroxidase (HRP) conjugate indicated that mouse IgG could be quantitatively detected in the range of 0-100 ng/ml, demonstrating the applicability of vertical microfluidic operation to the immunoassay.

PubMed

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

We developed an enzyme-linked immunosorbent assay for an endocrine disrupter, nonylphenol, using a microreactor composed of two reaction vessels stacked vertically through a microfluid filter. The filters constructed by deep X-ray lithography possessed 2100 through-bores (phi40 x 200 microm) in polymethylmethacrylate sheets (phi3 mm), which are appropriate for biochemical reactions. Through the optimization of the immunoassay, nonylphenol was quantitatively detected at the range of 0.1-10 ng/ml.

PubMed

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

DOI： 10.1007/s00542-006-0218-8

Event date： 2023.11

Language：English   Presentation type：Oral presentation(invited, special)  

Venue：Phan Thiet   Country：Viet Nam  

Event date： 2023.11

Language：Japanese   Presentation type：Poster presentation  

Event date： 2023.11

Language：Japanese   Presentation type：Poster presentation  

Event date： 2023.11

Language：Japanese   Presentation type：Poster presentation  

Event date： 2023.11

Language：Japanese   Presentation type：Poster presentation  

Event date： 2023.10

Language：English   Presentation type：Poster presentation  

Country：Poland  

Event date： 2023.10

Language：English   Presentation type：Poster presentation  

Country：Poland  

Event date： 2023.10

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Event date： 2023.6

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2023.5

Language：Japanese   Presentation type：Poster presentation  

Event date： 2023.5

Language：Japanese   Presentation type：Poster presentation  

Event date： 2022.12

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2022.12

Language：Japanese   Presentation type：Poster presentation  

Event date： 2022.11

Language：Japanese   Presentation type：Poster presentation  

Venue：アスティとくしま  

Event date： 2022.11

Language：Japanese   Presentation type：Poster presentation  

Event date： 2022.11

Language：Japanese   Presentation type：Poster presentation  

Venue：アスティとくしま  

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：富山大学五福キャンパス  

Event date： 2022.9

Language：Japanese   Presentation type：Poster presentation  

Venue：富山大学五福キャンパス  

Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：山梨大学（ハイブリッド）  

Event date： 2022.8

Language：Japanese   Presentation type：Poster presentation  

Venue：オンライン  

Event date： 2022.8

Language：English   Presentation type：Oral presentation(general)  

Event date： 2022.7

Language：English   Presentation type：Oral presentation(invited, special)  

Language：English   Presentation type：Oral presentation(invited, special)  

Event date： 2022.3

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：オンライン  

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Venue：オンライン  

Event date： 2021.7

Language：English   Presentation type：Oral presentation(invited, special)  

Language：English   Presentation type：Oral presentation(invited, special)  

Event date： 2021.7

Language：English   Presentation type：Poster presentation  

Language：English   Presentation type：Poster presentation  

Event date： 2020.12

Language：English   Presentation type：Oral presentation(invited, special)  

Venue：on-line  

Language：English   Presentation type：Oral presentation(invited, special)  

Venue：on-line  

Event date： 2020.11

Language：English   Presentation type：Oral presentation(general)  

Language：English   Presentation type：Oral presentation(general)  

Venue：オンライン  

Event date： 2020.3

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2020.3

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：上智大学　四谷キャンパス  

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：上智大学 四谷キャンパス  

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2020.3

Language：Japanese   Presentation type：Poster presentation  

Venue：上智大学　四谷キャンパス  

Event date： 2020.3

Language：Japanese   Presentation type：Poster presentation  

Venue：上智大学　四谷キャンパス  

Event date： 2020.3

Language：Japanese   Presentation type：Poster presentation  

Venue：上智大学　四谷キャンパス  

Language：Japanese   Presentation type：Poster presentation  

Venue：上智大学 四谷キャンパス  

Language：Japanese   Presentation type：Poster presentation  

Venue：上智大学 四谷キャンパス  

Language：Japanese   Presentation type：Poster presentation  

Venue：上智大学 四谷キャンパス  

Event date： 2019.10

Language：English   Presentation type：Poster presentation  

Venue：Basel, SWITZERLAND  

Event date： 2019.10

Language：English   Presentation type：Poster presentation  

Venue：Basel, SWITZERLAND  

Language：English   Presentation type：Poster presentation  

Venue：Basel, SWITZERLAND  

Language：English   Presentation type：Poster presentation  

Venue：Basel, SWITZERLAND  

Event date： 2019.9

Language：English   Presentation type：Poster presentation  

Venue：Rhodes Greece  

Language：English   Presentation type：Poster presentation  

Venue：Rhodes Greece  

Event date： 2019.5

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学　宝町・鶴間キャンパス 十全講堂  

本発表は、高スループット分子間相互作用解析技術の開発に関する発表であり、本手法に用いる生体分子固定化基板の表面設計に関する報告である。特に生体分子固定化の足場となるアミンの密度に対する生体分子間相互作用の力学測定結果の依存性を報告した。

Event date： 2019.5

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学　宝町・鶴間キャンパス 十全講堂  

本発表は、安価な部品から構成される自立制御型マイクロ流体システムの制御装置を開発し、この免疫測定への適用を評価したものである。

Event date： 2019.5

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学　宝町・鶴間キャンパス 十全講堂  

本発表は、自立制御型マイクロ流体デバイスによる血球分離プロセスにおいて、BOYCOTT効果を導入することにより、分離速度の向上を試みた研究の成果を報告したものである。

Event date： 2019.5

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学　宝町・鶴間キャンパス 十全講堂  

本発表は、自立制御型マイクロ流体デバイスに置いて両面成形プロセスを適用することで３次元交差マイクロ流路ネットを形成したデバイスに関するものである。特に、試薬分注機構の高精度化に焦点を当てた成果報告であり、両面成形プロセスを使用しない場合との精度比較結果を報告したものである。

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学 宝町・鶴間キャンパス 十全講堂  

本発表は、自立制御型マイクロ流体デバイスによる血球分離プロセスにおいて、BOYCOTT効果を導入することにより、分離速度の向上を試みた研究の成果を報告したものである。

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学 宝町・鶴間キャンパス 十全講堂  

本発表は、自立制御型マイクロ流体デバイスに置いて両面成形プロセスを適用することで３次元交差マイクロ流路ネットを形成したデバイスに関するものである。特に、試薬分注機構の高精度化に焦点を当てた成果報告であり、両面成形プロセスを使用しない場合との精度比較結果を報告したものである。

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学 宝町・鶴間キャンパス 十全講堂  

本発表は、安価な部品から構成される自立制御型マイクロ流体システムの制御装置を開発し、この免疫測定への適用を評価したものである。

Language：Japanese   Presentation type：Poster presentation  

Venue：金沢大学 宝町・鶴間キャンパス 十全講堂  

本発表は、高スループット分子間相互作用解析技術の開発に関する発表であり、本手法に用いる生体分子固定化基板の表面設計に関する報告である。特に生体分子固定化の足場となるアミンの密度に対する生体分子間相互作用の力学測定結果の依存性を報告した。

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Oral presentation(general)  

Language：Japanese   Presentation type：Poster presentation  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Event date： 2019.3

Language：English  

Event date： 2019.3

Language：English  

Language：English  

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Language：English  

Event date： 2019.1

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Language：Japanese   Presentation type：Oral presentation(invited, special)  

Event date： 2018.11

Language：English   Presentation type：Poster presentation  

Venue：Taiwan  

Event date： 2018.11

Language：English   Presentation type：Poster presentation  

Venue：Taiwan  

Language：English   Presentation type：Poster presentation  

Venue：Taiwan  

Language：English   Presentation type：Poster presentation  

Venue：Taiwan  

Event date： 2018.10

Language：English   Presentation type：Poster presentation  

Venue：Sendai  

Language：English   Presentation type：Poster presentation  

Venue：Sendai  

Event date： 2018.9

Language：Japanese   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Poster presentation  

Application no：特願2019-551166 

Patent/Registration no：CN111247433  Date registered：2023.5