We developed a microfluidic device that enables selective droplet extraction from multiple droplet-trapping pockets based on dielectrophoresis. The device consists of a main microchannel, five droplet-trapping pockets with side channels, and drive electrode pairs appropriately located around the trapping pockets. Agarose droplets capable of encapsulating biological samples were successfully trapped in the trapping pockets due to the difference in flow resistance between the main and side channels. Target droplets were selectively extracted from the pockets by the dielectrophoretic force generated between the electrodes under an applied voltage of 500 V. During their extraction from the trapping pockets, the droplets and their contents were exposed to an electric field for 400–800 ms. To evaluate whether the applied voltage could potentially damage the biological samples, the growth rates of Escherichia coli cells in the droplets, with and without a voltage applied, were compared. No significant difference in the growth rate was observed. The developed device enables the screening of encapsulated single cells and the selective extraction of target droplets.

We have developed an efficient, stable device for generating single-micrometer-scale (1-2 mu m) droplets based on the fragmentation of droplet tails by tailing. The device, created by a simple soft lithography process, induced continuous droplet fragmentation by branched channels under low-flow conditions (1-10 mu L/min). The flow rate and surfactant concentration were also important factors for droplet fragmentation. Examining 10 combinations of flow rate and surfactant concentration revealed the optimal conditions, which produced droplets less than 2 mu m in size at a generation rate of 61.1%. With this method, we efficiently encapsulated cell-mimicking microbeads into passively generated single-micrometer-scale microdroplets.

For high throughput size controllable micro droplet generation, a three step half and half size/volume division of source droplet device using three stage cascade channel is introduced. Passive and active size/volume ratio controllable source droplet division devises are reported next. Finally, two types of microdroplet (daughter) generation devices using hydrodynamic droplet breakup of source droplet (mother) are described.

In recent years, research on the application of microdroplets in the fields of biotechnology and chemistry has made remarkable progress, but the technology for the stable generation of single-micrometer-scale microdroplets has not yet been established. In this paper, we developed an efficient and stable single-micrometer-scale droplet generation device based on the fragmentation of droplet tails, called “tail thread mode”, that appears under moderate flow conditions. This method can efficiently encapsulate microbeads that mimic cells and chemical products in passively generated single-micrometer-scale microdroplets. The device has a simple 2D structure; a T-junction is used for droplet generation; and in the downstream, multi-branch channels are designed for droplet deformation into the tail. Several 1–2 µm droplets were successfully produced by the tail’s fragmentation; this continuous splitting was induced by the branch channels. We examined a wide range of experimental conditions and found the optimal flow rate condition can be reduced to one-tenth compared to the conventional tip-streaming method. A mold was fabricated by simple soft lithography, and a polydimethylsiloxane (PDMS) device was fabricated using the mold. Based on the 15 patterns of experimental conditions and the results, the key factors for the generation of microdroplets in this device were examined. In the most efficient condition, 61.1% of the total droplets generated were smaller than 2 μm.

We fabricated a microfluidic device with a three-dimensional (3D) structure and verified its droplet-generation performance for the stable production of droplets of around 10 μm in size. We compared the performance of the 3D device with that of conventional simple T-junction and cross-junction structures. The continuous phase sheared the dispersed phase into droplets from eight directions in the 3D device, compared with only one direction in the T-junction device and two in the cross-junction device. Droplets were produced efficiently over a wide range of fluid properties and flow conditions with the 3D device, unlike with the two conventional planar devices. Fluidic experiments were conducted using mineral oil with a surfactant as the continuous phase, deionized (DI) water as the dispersed phase, and DI water with glycerin to change the viscosity of the dispersed phase. The minimum droplet length was 47.2 μm in the T-junction device, 39.0 μm in the cross-junction device, and 22.4 μm in the 3D device when using a water and glycerin mixture with a viscosity of 9.0 mPa·s. Compared with the conventional devices, smaller droplets were produced using our 3D device, indicating that it has excellent droplet-generation performance.

This study uses vacuum ultraviolet (VUV) light with a wavelength of 172 nm as a surface treatment to enhance the adsorption capacity of wood-based activated carbon (AC). The AC surface treatment is performed under three O2 partial pressure conditions—5.0 × 104 Pa, where ozone (O3) effects dominate; 6.3 × 10−6 Pa, where VUV effects dominate; and 1.9 × 103 Pa for a balanced condition. For the O3-dominant condition, only graphene edge defects are etched (no aromatic carbon bonds are etched), resulting in increased surface roughness. When the VUV effects dominate, aromatic carbon bonds are cleaved, which then reacted with O2 or water adsorbed inside the pores. This increased both the number and size of the mesopores. Under the balanced conditions, the water adsorption capacity was enhanced by 45.5%, which is higher than that obtained before VUV exposure or with VUV under other conditions. This is because the surface roughness increased, as well as the pore sizes and numbers under the balanced condition. These results indicate that we can control VUV-based AC surface treatments via O2 partial pressure.

Fish-derived collagen is considered a promising material for oral mucosa tissue engineering because it is free from risk of transmissible infectious diseases. We developed a novel fish scale collagen scaffold with micropatterns on which oral keratinocytes are cultured to create a tissue-engineered oral mucosa. Anisotropic and isotropic etching were used to fabricate negative patterns on the Si substrate and soft lithography was used to translate the patterns to PDMS and fish scale collagen. The histological evaluation of the tissue-engineered oral mucosa confirmed the successful formation of the epithelial layer mimicking oral mucosa in vivo. This study suggests that our novel approach for fabricating biomimetic scaffold is promising and will make a huge contribution to the field of oral mucosa regeneration.

We developed an RGB microfluidic quantum dots light-emitting diode (QLED). All emitter and luminophores were liquid materials, including liquid organic semiconductor (LOS) as a backlight and quantum dots (QDs) solutions for high-color-purity luminophores. A deep-blue LOS backlight was used to excite QDs solutions. RGB lights were achieved with narrow full width at half maximum (FWHM) of 26.2 nm (green) and 25.0 nm (red), and were close to the boundary of CIE color space. The color purity of the RGB microfluidic QLED was the highest in that of ever reported LOS based devices. The proposed device is expected to provide future flexible displays with high-color-purity.

This work describes an on-chip mixer for post-column derivatization after liquid chromatography (LC) separation. The mixer was developed as a microchannel filled with a diamond-shaped pillar array (pillar array mixer, PA-mixer), which simultaneously enhanced the derivatization reaction and prevented the diffusion of the separated analytes. By utilizing the LC chip with a PA-mixer, neurotransmitters that are otherwise undetectable without derivatization could be separated, derivatized with a fluorogenic reagent, and detected within 15 s. In this manner, an automated bioanalytical method for point-of-care diagnosis was made possible by using the LC chip.

We have developed a deformability-based microfluidic microdroplet method for screening microbial cells secreting macromolecule-degrading enzymes. In this method, microbial cells are encapsulated as single cells in water-in-oil (W/O) microdroplets with macromolecule, whose shape becomes deformable as the macromolecule is progressively degraded into smaller molecules. Screening is achieved using a microfluidic device that passively sorts the deformed W/O microdroplets. Using this method, we successfully sorted agarose-containing microdroplets encapsulating single bacterial cells that hydrolyze agarose.

We proposed microfluidic quantum dots light-emitting diodes using a liquid organic semiconductor (LOS) and quantum dots (QDs) solutions. LOS and QDs solutions were used as a backlight and a luminophore, respectively. Channels for the QDs solutions were stacked on the LOS backlight. With applying voltage, red photoluminescence (PL) emissions of the QDs solution excited by the LOS backlight, was observed. The full width at half maximum of the red-PL emission was 29.8 nm, which is narrower than that of the LOS backlight by 40%. The proposed device is expected to provide highly-bright flexible displays with high-color-purity.

Recently, we developed Cu-Cu quasi-direct bonding with Pt intermediate layer deposited by atomic layer deposition (ALD). In this report, we study about a role of inserted Pt layer deposited by ALD. The improvement of bonding strength by quasi direct bonding was explained by two kinds of mechanisms.

A low temperature Cu-Cu bonding technique using an atomically thin-Pt intermediate layer deposited by atomic layer deposition (ALD) was recently reported. In this study, we investigated the characteristic of the Cu-Cu quasi-direct bonding using different metal intermediate layers. A thin-Pt or Au intermediate layer were deposited on the Cu surface by ALD in angstrom level. Both the thin-Pt and the Au intermediate layer successfully improved the Cu-Cu bonding strength compared with that without thin-metal intermediate layer. Although Au is widely used as a thick-intermediate layer in conventional Cu-Cu bonding methods, the Cu-Cu quasi-direct bonding with thin-Pt layer obtained three times lager bonding strength (9.52 MPa) than that with thin-Au layer (3.20 MPa). These results are essential for developing low temperature Cu-Cu bonding for highly integrated 3D IC chips.

We propose a low temperature bonding technique using an ultrathin intermediate layer deposited by atomic layer deposition. The ultrathin Pt film is selectively deposited on Cu surfaces without any masks. In order to reduce a deterioration of a reliability caused by impurities in the bonding interface, quasi-direct bonding was realized by thinning Pt intermediate layer. The shear strength of Cu-Cu bonding with the Pt intermediate layer achieved 9.5 MPa, which was five times higher than that without the Pt intermediate layer. We expect that the proposed bonding technique has a high potential to low temperature packaging technologies.

We developed a fabrication method of high-aspect-ratio fine vias with a build-up resin. The build-up resin composed of a thermosetting resin and silica fillers has low coefficient of thermal expansion and low dielectric constant. Thermal imprint was performed to form the high-aspect-ratio fine via holes on the build-up resin. The imprint mold with high-aspect-ratio fine pillar patterns was fabricated by photolithography and deep reactive ion etching. The residual layer consisted of the thermosetting resin and the silica filler was removed by O2/CHF3 plasma etching. The via of 1.2 μm in diameter with aspect ratio of 5.5, and 5.0 μm in pitch was successfully fabricated followed by Au electroplating. The proposed fabrication method is applicable for high-density 3-dimensional and 2.5-dimensional integration technologies.

We proposed an efficient and high throughput formation process for single-micron order droplets using breakup of droplet tail. Droplet tail was induced by multi-branch channel, and several daughter droplets about 1-2 μm in diameter were continuously generated by splitting of the tail at the branch channel. An effect of chemical assistances on the tail and daughter droplet formation was evaluated, as well as influence of fluidic conditions.

In this study, microdroplets are regarded as a “small laboratory”, and complex chemical azo compound was firstly synthesis. The synthesis of azo compounds requires accurate pH control. Furthermore, the reaction is accompanied by heat generation. Synthesis applying microdroplets has advantages over temperature control (ice cold→room temperature (23℃)), pH reagent concentration (5.62 molL-1→0.50 molL-1), synthesis time (3,600 sec→4 sec), and recrystallization work was not necessary. The microdroplet rapidly released heat and no side reaction due to heat occurred. The microdroplet method enables accurate pH control and enables highly pure synthesis.

This research presents a sequential formation method of microdroplets whose volumes are uniform or arithmetically distributed. Side flow into bypass channel allows fine breakup of daughter droplets and volumes of the droplets are controlled via dimension of the bypass channels. Rejoining of the bypass channel with main channel provides uniform initial condition before all situation of droplet breakup. Therefore, the two types of channel design achieves precise formation of multiple daughter droplets continuously.

We developed a water-electrokinetic energy harvester using a flexible woody carbon film (FWCF). The proposed device induced streaming current/voltage by water-vapor flow and thermal-evaporation flow in natural microchannels of wood, which called tracheid. In addition, high specific area of the FWCF can improve the output. The fabricated device showed a streaming voltage of about 9.7\\ \\mu \\mathrm{V} with the water-vapor flow. Moreover, the output of the device were enhanced by thermal-evaporation flow. The maximum output voltage was 421.3\\ \\mu \\mathrm{V}. After stabilization, 217.8\\ \\mu \\mathrm{V} was continuously observed over 30 minutes at 80 °C. These results indicate that the proposed FWCF based water-electrokinetic power generation device has a high potential in power sources for Internet of things society.

This paper reports design optimization of vibration based energy harvest device fabricated by simple printing and laminating process using polymeric piezoelectric material (VDF/TrFE). Modified trapezoidal design increased the output voltage and energy dramatically by adhesion strength as well as improvement of internal stress distribution of the device. The process guaranteed simple (fast and low cost) fabrication of energy harvest device and the new design achieved 277 V and 1014 nJ outputs which is about 3 times higher than that of our previous device. Furthermore, by stacking the devices and connecting them in parallel, we increased the output energy into about 2.58μ J.

Immune cells communicate with each other to regulate their activity. Cytokines are humoral proteins secreted and received by specific cells as one of the communication media. Although several single-cell techniques to measure the cytokine secretion have been reported, it is still hard to simultaneously monitor the secretion activity and motility of individual cells composing a cell community. Previously, we have developed the platform of wide-field LCI-S (live-cell imaging for secretion activity) with the open-spaced cell culture chamber on the optical waveguide. We have monitored type2 cytokine secretion and motility from hundreds of ILC2s (Group 2 innate lymphoid cells). Here, we conducted a detailed analysis of the obtained data to reveal the relevance between cell migration patterns and cytokine secretion dynamics of migrating cells. We tracked each cell on bright field images and found two types of cell migration features: directional and random motilities. We also estimated the production amount of the secreted cytokine at each time point by calculating the serial cumulative images of secreted cytokine. By combining these data, we succeeded in examining the relationship between motility and secretion activity. These results demonstrated that wide-field LCI-S has the potential to elucidate immune cells' behavior as a cell population that is regulated by cell-To-cell communication via humoral factors.

We developed highly bendable transparent indium tin oxide (ITO) electrodes with a mesh pattern for use in flexible electronic devices. The mesh patterns lowered tensile stress and hindered propagation of cracks. Simulations using the finite element method confirmed that the mesh patterns decreased tensile stress by over 10% because of the escaped strain to the flexible film when the electrodes were bent. The proposed patterned ITO electrodes were simply fabricated by photolithography and wet etching. The resistance increase ratio of a mesh-patterned ITO electrode after bending 1000 times was at least two orders of magnitude lower than that of a planar ITO electrode. In addition, crack propagation was stopped by the mesh pattern of the patterned ITO electrode. A mesh-patterned ITO electrode was used in a liquid-based organic light-emitting diode (OLED). The OLED displayed the same current density-voltage-luminance (J-V-L) curves before and after bending 100 times. These results indicate that the developed mesh-patterned ITO electrodes are attractive for use in flexible electronic devices.

We developed a novel naphthalene derivative to function as a wide-energy-gap liquid organic semiconductor (LOS) host material for the limited range of liquid deep-blue light-emitting materials that have been developed to date. The naphthalene derivative 1-naphthaleneacetic acid 2-ethylhexyl ester (NLQ), which shows a low viscosity of 20 mPa·s at 25 °C, was synthesized as a LOS by introducing an ethylhexyl group into naphthalene. We doped 9,10-diphenylanthracene (DPA) into NLQ as a guest deep-blue dye. The highest occupied molecular orbital (HOMO) energy level of NLQ was estimated to be − 6.40 eV from photoelectron spectroscopy measurements in air. The energy gap of NLQ was estimated to be 4.08 eV from its absorption spectrum, indicating that NLQ has the widest energy gap of any such host material to date. The lowest unoccupied molecular orbital energy level of NLQ was calculated to be − 2.31 eV. Deep-blue electroluminescence emission in a liquid state was obtained by doping DPA into NLQ. Light emission could be achieved by a combination of Förster resonance energy transfer and direct recombination of trapped holes and electrons because the energy gap of DPA is straddled by the wider energy gap of NLQ.

Copper-copper (Cu-Cu) direct bonding assisted by direct immersion gold (DIG) was demonstrated. Cu-Cu direct bonding is a critical technology for inductively coupled memory interconnections. To solve the problems of conventional methods of Cu-Cu direct bonding, a plating process using DIG to form an intermediate layer was selected. The concept of the developed bonding process is to use deformation of DIG to compensate for the surface roughness of the Cu substrates during application of pressure and annealing. Using this method, precise surface flattening of Cu substrates is not necessary. Bonding can be achieved even in an air atmosphere. A sample bonded at a temperature of 350°C failed within the chip in a shear test. It was found that bonding can be achieved when the gold (Au) thickness is greater than the half of the surface roughness of Cu at the bonding temperature. Transmission electron microscopy-energy-dispersive x-ray spectroscopy revealed that Au diffused into Cu during bonding. The diffusion constant of Au into Cu was investigated through a numerical calculation. The obtained results showed good agreement with the literature values.

This paper presents mechanically reinforced low-concentration alginate fibers by embedding inner cores of high-concentration alginate. 3D structures by stacking multiple polydimethylsiloxane (PDMS) layers allow the microfluidic formation and control of the isolated cores in the continuous flow. The alginate hydrogel fibers are simply spun, and the compartments, central core, surrounding cores, and outer shell layer are successfully verified. The results demonstrate the great potential for the development of complex fibrous materials, particularly for biological applications, which require specific morphology and composition of the fibers.

A direct bonding of poly(oxymethylene) (POM) was feasible at 100 °C by using self-assembled monolayer (SAM) as a surface modification method. (3-aminopropyl)triethoxysilane (APTES) and (3-glycidyloxypropyl)trimethoxysilane (GOPTS) were used in our work. X-ray photoelectron spectroscopy showed that both APTES and GOPTS modified the POM surface successfully. Bonding strength evaluation revealed that surface modification was affected by pretreatment (VUV/O3) process time. In addition, the bonding condition with highest strength had an average strength of 372 kPa. This technology is expected to be used in packaging for micro-/nano-electromechanical systems, such as biomedical devices.

We developed an oil-in-water droplet formation method in a 3D stacked PDMS device without hydrophilic treatment using structural feature only. Three-dimensional junction shape of oil-water phase injection channels suppressed contact and spreading of oil on the wall surface which was critical problem of droplet formation for unfavourable wetting condition. Dimension of droplets formed under various flow conditions was provided and effects of each channel's shape on the droplet formation results were evaluated. The proposed structure can be used as a droplet generator and element for droplet based researches employing various materials.

Direct heterogeneous bonding between polyether ether ketone (PEEK) and Pt was realized at the temperatures lower than 150 C-omicron. In order to create sufficient bondability to diverse materials, the surface was modified by vacuum ultraviolet (VUV) irradiation, which formed hydrate bridges. For comparison, direct bonding between surfaces atomically cleaned via Ar fast atom bombardment (FAB) was conducted in a vacuum. The VUV irradiation was found to be effective for creating an ultrathin hydrate bridge layer from the residual water molecules in the chamber. Tight bonds were formed through dehydration of the hydrate bridges by heating at 150 C-omicron, which also contributed to enhancing interdiffusion across the interface. The VUV-modified surfaces showed bondability as good as that of the FAB-treated surfaces, and the VUV-modified samples had shear strengths at the same level as those of FAB-treated surfaces. This technology will be of practical use in the packaging of lightweight, flexible biomedical devices. (C) 2017 Elsevier B.V. All rights reserved.

An ex vivo brain lactic acid (LA) monitoring system for investigating brain activity at the organ level was constructed and tested in continuous LA monitoring. Our system consists of a micro-fluidic dual-analyte (LA and glucose) biosensor and a special brain chamber that is suitable for organ level experiments. The biosensor utilizes the redox reactions of osmium-wired horseradish peroxidase (Os-HRP) to detect hydrogen peroxide produced by enzyme reactions. The sensor had sufficient sensitivity (LA: ∼ 0.01 mM, glucose: ∼ 0.01 mM) and selectivity for assessment of extracellular LA. The ex vivo monitoring of brain LA was performed using the proposed system. As a result, the change in extracellular LA was successfully monitored continuously, and the change in the LA level was considered the result of metabolic activity of the sample. Our system is expected to be useful not only for ex vivo brain monitoring, but also for monitoring other organs.

A fully passive volume-dependent droplet sorter is presented in this research. Repeated and multiple on-rail transfer of microdroplets in a cascade channel resulted in high resolution sorting of droplet-phase samples. Microdroplets with volumes of 0.89-3.26 nl were successfully sorted in eight steps, and a maximum sorting resolution of about 0.21 nl was obtained over three transfer stages. Line rails and dot rails employed in the cascading channels allowed volume-dependent droplet transfer, and shape recovery of the transferred droplet for the repeatable transfer, respectively. This simple device and method can be applied to droplet-based chemical or biological research.

We propose hermetic sealing of a glass-to-glass structure with an I-structure through-glass interconnect via (TGV) filled with submicron Au particles. The top and bottom bumps and the TGV were formed by a simple filling process with a bump-patterned dry film resist. The sealing devices consisting of two glass substrates were bonded via Au interlayers. Vacuum ultraviolet irradiation in the presence of oxygen gas (VUV/O-3) pretreatment was used for low-temperature Au-Au bonding at 200 degrees C. The bonded samples showed He leakage rates of less than 1.3 x 10(-9) Pa m(3) s(-1). The cross-sectional scanning electron microscope images of the fabricated I-structure TGV showed perfect adhesion between the I-structure TGV and glass substrate. These results indicate that the proposed I-structure TGV is suitable for hermetic sealing devices.

We present fabrication and testing of bottom-emitting organic light-emitting diode (OLED) panels based on flip chip assembly and non-destructive scanning. In this method, the OLED and electric circuits are fabricated on separate substrates and interconnected by low temperature assembly to create a high-performance bottom emitting OLED including other functions such as thin-film transistor (TFT) circuits. The low temperature assembly process consists of two steps. First, an OLED substrate and encapsulation glass with circuits are bonded at 100 degrees C via Au-Au bond. Encapsulation glass is utilized for the functional substrate with circuits. Next, the bonded panel is sealed by capillary underfill within and by applying and curing seal materials to the panel edge. The fabricated OLED was non-destructively evaluated by scanning acoustic microscopy (SAM). The SAM image shows all phi 500 mu m Au bumps were bonded to Au pads, indicating that OLED and encapsulation substrates were assembled. Electroluminescence of the OLED was demonstrated by applying voltage. Stable current-luminance characteristics were obtained for the fabricated OLED with an operating voltage of 3.25 V. The results indicate that the proposed fabrication is available for bottom-emitting OLED controlled by TFT circuits. In future, the assembly process can be widely applied to other flexible organic electronic devices with roll assembly by altering OLED or circuits with other devices because this is a simple pressure method with low temperature, achieving encapsulation at same time. (C) 2016 Elsevier B.V. All rights reserved.

A microfluidic stamping method to form functional shapes on a cross section in fibre-shaped flow is presented by D. H. Yoon and co-workers on page 3224. Microfluidic stamping and overstamping allowed various cross sectional shapes on the three-dimensional flow. Dimension of the flows is controlled via a change in combination of 3D structures and fluidic conditions, which correspond to stamp type and stamping force.

A microfluidic stamping method to form functional shapes on a cross section in fiber-shaped flow is proposed. Microfluidic stamping and overstamping allow various cross sectional shapes on the 3D flow. The shapes can be controlled by a change in combination of structures and fluidic conditions which correspond to stamp type and stamping force.

To realize efficient, fast separations on pillar array columns with turns, a novel turn with low-dispersion and low-pressure-drop properties was developed. This "pillar-distribution controlled" (PDC) turn was designed as a constant-radius-turn filled with octagonal pillars that were arranged to control the linear velocity of the mobile phase in the radial direction. After the pillar positions were adjusted by computational fluid dynamics analysis, 27 mm long pillar array columns with two turns were fabricated on a 20 x 20 mm(2) silicon glass plate. The PDC turns suppressed the sample dispersion to a similar extent as the previously developed tapered turn, and the pressure drop of the newly designed turn was reduced to similar to 1/6 that of the tapered turn. Moreover, the C18-modified pillar array column with the PDC turns showed good bioanalytical applicability; five fluorescendy labeled amino acids were separated in only 24 s at a linear velocity of 7.5 mm/s. The developed turn structure offers the advantages of longer pillar array columns with more turns for the fast analysis of complex samples.

Environmental microbes are a great source of industrially valuable enzymes with potent and unique catalytic activities. Unfortunately, the majority of microbes remain unculturable and thus are not accessible by culture-based methods. Recently, culture-independent metagenomic approaches have been successfully applied, opening access to untapped genetic resources. Here we present a methodological approach for the identification of genes that encode metabolically active enzymes in environmental microbes in a culture-independent manner. Our method is based on activity-based single-cell sequencing, which focuses on microbial cells showing specific enzymatic activities. First, at the single-cell level, environmental microbes were encapsulated in water-in-oil microdroplets with a fluorogenic substrate for the target enzyme to screen for microdroplets that contain microbially active cells. Second, the microbial cells were recovered and subjected to whole genome amplification. Finally, the amplified genomes were sequenced to identify the genes encoding target enzymes. Employing this method, we successfully identified 14 novel beta-glucosidase genes from uncultured bacterial cells in marine samples. Our method contributes to the screening and identification of genes encoding industrially valuable enzymes.

This paper reports 50-s liquid chromatography (LC) separation of oxidative stress markers using an amide-modified pillar array column (PAC). The amide modification enables a sufficient retention of highly polar compounds under hydrophilic interaction LC (HILIC) conditions, and five fluorescence-labeled biothiols, i.e., cysteine, homocysteine, glutathione, cysteinylglycine, and N-acetylcysteine, in human plasma could be rapidly separated. Since these biothiols are associated with many diseases, this newly developed method could be a useful tool for the diagnosis or clinical investigation of biothiol-related diseases.

We developed functional sheath flow of specific cross section using 3D stacked PDMS structure. The device was fabricated by four layer PDMS structures consist of two cylindrical channels with cross injection inlets. In the multi-stacked 3D device, check-like cross section on a cylindrical flow was successfully formed and 100μm diameter alginate fiber of single core divided into four parts was achieved.

We conducted an experiment on the fabrication of fluidic devices for producing fine droplets. In our proposed method, multiple channels were fabricated by using a focused ion beam (FIB) system. The minimum feature top width was found to be approximately 56 nm. When both the target width and depth of one channel were set to 500 nm, the resultant top width was 750-780 nm, the bottom width was 250-320 nm, and the depth was 560 nm, almost achieving the target size for the channel depth.

This paper presents a simple printing process to design a novel piezoelectric energy harvest device made from (VDF/TrFE) copolymers. The fabrication process using metal nano-ink and a household printer dramatically reduced the fabrication complexity. Additionally, this process employed low temperatures and thus the structural damage of the polymers resulting from high temperature annealing could be avoided. An electric power of about 0.06 mu J was generated using this device.

Previously, we have developed a gradient elution system for pillar array columns, which achieved faster separation than isocratic elution. In this study, we validated gradient elution in microchip liquid chromatography (LC) and investigated the retention and bandwidth predictions of fluorescently labeled aliphatic amines in fast gradient elution chromatography using semi-empirical retention models. The retention times and peak widths under different gradient elution programs were predicted by three solvent strength models and compared with the experimental results. The relative errors of prediction for the retention times and peak widths were below 14 % and 12 %, respectively. The results showed that the solvent strength models could be utilized for predicting the retention times and peak widths under gradient elution in the microchip LC system and that the gradient elution program for pillar array columns worked efficiently. The prediction by the retention model promises to be a potential tool for essential compound identification in biological samples.

Efficient microfluidic synthesis of chiral salen Mn(II) and Co(II) complexes containing lysozyme was achieved. The reaction conditions for the delicate protein were controlled precisely with a separation barrier in the microfluidic device. The microfluidic method has the following advantages over the conventional method: a remarkable reduction in the reaction time from 4.5 h to less than 1 s for the synthesis of Mn(II) and Co(II) complexes, a reduction in the reaction temperature from 40 to 23 degrees C, and no need for an N-2 atmosphere because all the reagents are isolated from the air. A three-fold yield improvement was achieved for Mn(II) and Co(II) complexes containing lysozyme compared with conventional synthesis.

We propose a novel fabrication methodology for a hermetic sealing device using an O2 plasma-assisted low temperature Intrinsic-Silicon (I-Si) and glass bonding technique. Glass substrates were used as the cap and base wafers, while I-Si was applied selectively to the contact surface of the cap wafer as an interlayer. A 180-μm-deep cavity was formed in the cap glass by wet etching using a double-layer (photoresist/I-Si) etching mask. I-Si/glass bonding was conducted at 200°C using an I-Si layer-covered glass wafer and a bare glass wafer. Water contact angle measurements and tensile test results showed that the bonding strength increased with promoting surface hydrophilicity through O2 plasma pretreatment. Moreover, scanning acoustic microscope observations revealed that I-Si/glass bonding was achieved successfully without significant voids. Our results indicate that the proposed method could become an indispensable technique for future functional hermetic sealing devices.

The future development of low-temperature and low-pressure bonding technology is necessary for fine-pitch bump application. We propose a bump structure using Ag nanoparticles as an intermediate layer coated on a fine-pitch Cu pillar bump. The intermediate layer is prepared using an efficient and cost-saving squeegee-coating method followed by a 100A degrees C baking process. This bump structure can be easily flattened before the bonding process, and the low-temperature sinterability of the nanoparticles is retained. The bonding experiment was successfully performed at 250A degrees C and 39.8 MPa and the bonding strength was comparable to that achieved via other bonding technology utilizing metal particles or porous material as bump materials.

We demonstrated a novel microfluidic white organic light-emitting diode (microfluidic WOLED) based on integrated sub-100-mu m-wide microchannels. Single-mu m-thick SU-8-based microchannels, which were sandwiched between indium tin oxide (ITO) anode and cathode pairs, were fabricated by photolithography and heterogeneous bonding technologies. 1-Pyrenebutyric acid 2-ethylhexyl ester (PLQ) was used as a solvent-free greenish-blue liquid emitter, while 2,8-di-tert-butyl-5,11-bis(4-tert-butylphenyl)- 6,12-diphenyltetracene (TBRb)-doped PLQ was applied as a yellow liquid emitter. In order to form the liquid white light-emitting layer, the greenish-blue and yellow liquid emitters were alternately injected into the integrated microchannels. The fabricated electro-microfluidic device successfully exhibited white electroluminescence (EL) emission via simultaneous greenish-blue and yellow emissions under an applied voltage of 100 V. A white emission with Commission Internationale de l'Eclairage (CIE) color coordinates of (0.40, 0.42) was also obtained; the emission corresponds to warm-white light. The proposed device has potential applications in subpixels of liquid-based microdisplays and for lighting.

We developed organic light-emitting diodes (OLEDs) with nanopatterned current flow regions using electron-beam lithography with the aim of suppressing singlet-polaron annihilation (SPA). Nanopatterns composed of lines and circles were used in the current flow regions of nano-line and nano-dot OLEDs, respectively. Excitons partially escape from the current flow regions where SPA takes place. As such, current densities where external quantum efficiencies were half of their initial values (J(0)) increased as line width and circle diameter were decreased to close to the exciton diffusion length. Circles were more efficient at enhancing exciton escape and increasing J(0) than lines. The J(0) increase in the nano-dot OLEDs containing nanopatterned circles with a diameter of 50 nm was approximately 41-fold that of a conventional OLED with a current flow region of 4 mm(2). The dependence of J(0) on the size and shape of the nanopatterns was well explained by an SPA model that considered exciton diffusion. Nanopatterning of OLEDs is a feasible method of obtaining large J(0). (C) 2015 AIP Publishing LLC.

This paper proposes a high-throughput, function-based screening approach of a metagenomic library for isolating novel microbial enzymes by droplet-based microfluidics. We used gel microdroplets (GMDs) dispersed in oil as picoliter-volume reaction vessels for lipolytic enzyme by encapsulating cells in individual GMDs. Using this approach, we monitored the growth of individual cells encapsulated in GMDs and assessed the enzyme reaction activities at the level of an individual GMD. We then applied this method to screen lipolytic enzyme genes from the metagenomic library constructed from soil collected from a quercus serrate forest of Mount Tsukuba, Ibaraki, Japan. In the workflow presented in this study, metagenomic library clones were encapsulated in 100-pL GMDs with a fluorogenic reporter substrate. A total of 67,000 metagenomic library clones can be screened in only 24 h with reduced consumption of reagents (i.e., < 10 mu L). As a result, we identified a novel lipolytic enzyme, EstT1, belonging to the EstD2 family of esterases and containing a putative signal peptide, which facilitates enzyme export and catalyzation of substrates in the periplasm. Our study demonstrates the potential of microfluidic GMDs as an efficient tool for metagenomic library screening of industrially relevant enzymes with the potential of significantly reducing the cost and time factors involved in successful practical application of microbial enzymes. (C) 2014 Elsevier B.V. All rights reserved.

This paper presents methods for the formation of hollow microcapsules and microlenses using multiphase microdroplets. Microdroplets, which consist of a gas core and an organic phase shell, were generated at a single junction on a silicon device without surface treatment of the fluidic channels. Droplet, core and shell dimensions were controlled by varying the flow rates of each phase. When the organic solvent was released from the organic phase shell, the environmental conditions changed the shape of the solidified polymer shell to either a hollow capsule or a microlens. A uniform solvent release process produced polymeric capsules with nanoliter gas core volumes and a membrane thickness of approximately 3 mu m. Alternatively physical rearrangement of the core and shell allowed for the formation of polymeric microlenses. On-demand formation of the polymer lenses in wells and through-holes polydimethylsiloxane (PDMS) structures was achieved. Optical properties of the lenses were controlled by changing the dimension of these structures.

We report a real time method to monitor the chemical reaction in microdroplets, which contain an organic dye, 5(6)-carboxynaphthofluorescein and a CdSe/ZnS quantum dot using fluorescence spectra. Especially, the relationship between the droplet size and the reaction rate of the two reagents was investigated by changing an injection speed.

Silicon-based solid-phase-extraction (SPE) integrated liquid chromatography (LC) was proposed in this research. The integrated chip allowed continuous operation of selective sample enrichment and chromatography by a simple flow switching process. The sample reservoir was filled with extraction beads after silicon chip fabrication, and then targets were selectively adsorbed onto the beads. Pillar arrays provided uniform and dense sample band, while the targets were released from the beads. The integrated chip achieved more than 160 times higher fluorescence intensity of samples compared to normal injection chips, and coumarin 525 and 545 were successfully separated in 30-mm-long LC channel within 1 min.

This research is study for passive single cell encapsulated droplet formation. E.coli substituted 6 μm micro beads were encapsulated to sub-micron droplets while microdroplets of different size were generated depending on the encapsulation by tip-streaming phenomenon. For the formation of tip streaming and single cell encapsulation, chemical and physical assistant was utilized. Approximately 80% of single cell encapsulated droplets were selectively collected by deterministic lateral displasement (DLD) structure.

Environmental microbes are a great source of industrially valuable enzymes with high and unique catalytic activities. However, a vast majority of microbes remain unculturable and thus are not accessible by culture-based methods. Here, we present a rapid and efficient method to screen and identify enzyme-encoding genes from environmental microbes in a culture-independent manner. This method combines activity-based single cell screening using microdroplets and single cell genomics. Using this method, we successfully identified 13 novel β-glucosidase genes from uncultured marine bacteria. This method will facilitate the identification of genes encoding industrially valuable enzymes.

In this study, we propose on-demand multi-color microfluidic organic light-emitting diodes (microfluidic OLEDs) using fluorescent guest emitter-doped liquid organic semiconductors. We use 1-pyrenebutyric acid 2-ethylhexyl ester (PLQ) not only for a greenish-blue liquid emitter, but also for a liquid host. 5,12-Diphenyltetracene (DPT), 5,6,11,12-tetraphenyltetracene (rubrene), and tetraphenyldibenzoperiflanthene (DBP) are doped into PLQ to obtain green, yellow, and red liquid emitters, respectively. Single-micrometer-thick SU-8-based microchannels sandwiched between an indium tin oxide (ITO) anode and a 3-aminopropyltriethoxysilane (APTES)-modified ITO cathode are fabricated on a glass substrate using photolithography and heterogeneous bonding techniques, and emitting layers are formed on-demand by simply injecting liquid emitters into the target microchannels. The microfluidic OLEDs with liquid emitters successfully exhibited multi-color electroluminescence (EL) emissions. Furthermore, the maximum luminance reached 26.0 cd/m&lt
sup&gt
2&lt
/sup&gt
at 61 V for 2.5-μm-thick microfluidic OLED with PLQ, and the decreased EL luminance was recovered by replacing the degraded emitting layer with a fresh liquid emitter. We expect that on-demand multi-color EL emissions and refreshable luminance features of the proposed microfluidic OLEDs will be highly promising technologies for future long-life light-emitting device applications.

This paper presents a droplet sampling device driven by horizontal pneumatic actuators. A high aspect ratio and highly flexible PDMS (polydimethylsiloxane) structure was proposed for carrying out larger number of sampling than the number of actuators. Large deformation of the actuators caused domino-deformation of parallel walls, and the deformations allowed for selective collection of target droplets. The dimensions of the PDMS structure and the ratio of resin to curing agent were optimized for efficient sampling under the low pressure applied to the actuators. Five sampling modes were achieved in the simple one-layer structure consisting of one inlet, four walls, one drain channel, and two pneumatic actuators, formed by single-step soft lithography process.

We report a novel real-time method to monitor the reaction of an organic dye, 5(6)-carboxynaphthofluorescein succinimidyl ester and a CdSe/ZnS quantum dot (QD) using fluorescence spectra of microdroplets formed in a microfluidic device. Dual fluorescence peaks (at lambda = 605 and 670 nm) were observed via a fluorescence energy transfer (FRET) process from the CdSe/ZnS QD to the organic dye; the rate of the chemical reaction of the two reagents was estimated by the ratio of the two fluorescence peaks, defined as the fluorescence intensity ratio. In addition, well-controlled microdroplets were continuously generated (with a diameter of similar to 150 mu m) in the microfluidic device and the reaction time was determined as the length from the mixing point to the sampling point using fluorescence spectroscopy. The fluorescence intensity ratio increased with increasing reaction time after mixing of the two reagents indicating that the chemical reaction was observed directly in the microdroplet. Therefore, the real-time monitoring of the chemical reaction was successfully achieved by measuring the fluorescence intensity ratio as a function of the reaction time. When compared with a conventional batch process, a fast reaction time of <1 s and a high fluorescence intensity ratio was achieved in the microdroplets formed in the microfluidic device. (C) 2014 Elsevier B.V. All rights reserved.

We propose simple and high-throughput fabrication of large-area flexible microfluidic organic light-emitting diodes (microfluidic OLEDs). Flexible electro-SU-8-microchannels with a liquid emission layer were fabricated by the following four steps: (a) screen printing for transparent electrodes, (b) novel belttransfer exposure for SU-8, (c) heterogeneous low-temperature bonding using self-assembled monolayers (SAMs), and (d) injecting a liquid emitter into the microchannels.1-Pyrenebutyric acid 2-ethylhexyl ester (PLQ), which is on of liquid organic semiconductors, was used as a liquid emitter. The liquid emitter successfully filled the flexible microchannels, and electroluminescence was obtained both in flat and curved states. The proposed microfluidic OLED is applicable for future flexible posters or displays, and can be adopted around curved surfaces. (C) 2014 Elsevier B.V. All rights reserved.

An electrohydrodynamic (EHD) ion-drag micropump using three-dimensional carbon micromesh electrodes was developed. The carbon micromesh electrodes were created by the pyrolysis of SU-8 structures. The carbon electrodes and microchannel were formed on a quartz substrate, and the microchannel was sealed by an SU-8 slab structure. The pumping behaviors were evaluated using Fluorinert as a non-conductive sample solution. The maximum pressure and volume flow rate were approximately 23 Pa and 400 nL/min, respectively, under an applied voltage of 500 V.

This paper describes a microdroplet merging device that can actively control the merging of various droplets under a wide range of flow conditions, using a simple structure. The microdroplets were trapped and merged in a wide chamber divided by pillars, and their behavior was controlled by two horizontal pneumatic microactuators. Hydrodynamic flow control by the actuation was evaluated numerically, and the trapping and merging of droplets were achieved experimentally and controlled via pressure applied to the microactuators. Furthermore, two independently generated droplets were merged under four different modes, ranging from no merging to four-droplet merging, with different ratios and volumes. The pneumatic actuators allowed not only the control of the number of merged droplets, but also a wide range of applied droplet volumes. The device was fabricated simply using a single-layer PDMS (polydimethylsiloxane) structure, and the continuous merging performance operated using only hydrodynamic flow control without any surfactant. Finally, chemical synthesis of a metal complex was performed by the droplet merging method. Crystallization of the complex was visualized in real time, and the synthesis was verified by ultraviolet-visible spectroscopy.

We demonstrated multi-color microfluidic electrochemiluminescence (ECL) cells. 5,6,11,12-Tetraphenylnaphthacene (rubrene), 9,10-diphenylanthracene (DPA), tetraphenyldibenzoperiflanthene (DBP)-doped rubrene, and 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) dissolved in a mixed organic solvent of 1,2-dichlorobenzene and acetonitrile in the ratio of 2:1 (v/v) were used as yellow, blue, red, and green ECL solutions, respectively. Light emissions were confirmed using simple-structured ECL cells consisting of two indium tin oxide (ITO) coated glass substrates with an SU-8 spacer of thickness varying from 0.9 to 6 mu m. The SU-8-based microfluidic ECL cells were fabricated using photolithography and heterogeneous bonding techniques through the use of epoxy-and amine-terminated self-assembled monolayers. The emitting layers were formed on-demand by injecting the chosen ECL solutions into the microchannels sandwiched between ITO anode and cathode pairs. Multi-color ECL was successfully obtained at the light-emitting pixels. The microfluidic ECL cells with DBP-doped rubrene solution showed a maximum luminance of 11.6 cd/m(2) and the current efficiency of ca. 0.32 cd/A at 8V. We expect that the proposed microfluidic device will be a highly promising technology for liquid-based light-emitting applications. (C) 2014 Elsevier B.V. All rights reserved.

In this paper, we describe a hybrid bonding technology of Au microbump and adhesive using a planar adhesive structure for 3-D large-scale integration (LSI). Hybrid bonding means that both the microbump electrode and adhesive are simultaneously bonded. In 3-D LSI, the gaps between bonded chips are <10 mu m because the pitch of the microbumps is decreased. Conventionally, adhesive resin is injected into the gaps by means of capillary force. However, the filling of the gaps is insufficient due to surface conditions. To address this challenge, we evaluated hybrid bonding with a planar adhesive structure fabricated by chemical-mechanical polishing. The bonding results showed that connection between the Au bumps and adhesive filling in the 6-mu m gap between bonded Si chips was achieved without readily visible void in the range of 6 mm x 6 mm. All 900 bumps were also electrically connected. The shear strength of the bonded sample was 13 MPa. Therefore, we determined that the proposed hybrid bonding technology is highly effective for 3-D LSI with fine-pitch microbumps.

We present a novel peptide-based ligand screening system for G protein-coupled receptors (GPCRs) in water-in-oil (W/O) microdroplets. This system is an in vitro gene screening system for peptides that activate a target GPCR expressed in yeast. We show that the system is applicable to human GPCRs. This system will be a powerful tool for identifying novel peptide ligands for liganded mammalian GPCRs and orphan mammalian GPCRs.

A rapid and quantitative method for the determination of phenylalanine (Phe) and tyrosine (Tyr) in plasma using pressure-driven liquid chromatography (LC) on a chip was developed. After derivatizing Phe and Tyr with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), separation was performed within 140 s on a previously developed integration chip with a pillar array column and a gradient elution system [1,2]. The Phe and Tyr in plasma were quantified and good validation data were obtained. As Phe and Tyr are considered to be important biomarkers of some diseases, especially for newborn screening, the developed method is promising for rapid diagnosis in the clinical field.

This paper presents a multiple size-oriented passive droplet sorting utilizing a balance between surface free energy and flow force. We proposed a simple multi-stage sorting structure which consists of a microchannel and guide grooves formed in parallel. Passive five different-sized droplets sorting of up to 200 droplets/s is achieved without any active elements. Also, we fabricated a prototype of the integrated micro fluidic system for droplet generation, merging and sorting for digital chemical synthesis.

In this study, a fast and quantitative determination method for branched-chain amino acids (BCAAs), namely leucine, isoleucine, and valine, was developed using a pillar array column. A pillar array column with low-dispersion turns was fabricated on a 20 x 20-mm(2) microchip using multistep ultraviolet photolithography and deep reactive ion etching. The BCAAs were fluorescently labeled with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), followed by reversed-phase separation on the pillar array column. The NBD derivatives of the three BCAAs and an internal standard (6-aminocaproic acid) were separated in 100 s. The calibration curves for the NBD-BCAAs had good linearity in the range of 0.4-20 mu M, using an internal standard. The intra- and interday precisions were found to be in the ranges of 1.42-3.80 and 2.74-6.97 %, respectively. The accuracies for the NBD-BCAA were from 90.2 to 99.1 %. The method was used for the analysis of sports drink and human plasma samples. The concentrations of BCAAs determined by the developed method showed good agreements with those determined using a conventional high-performance liquid chromatography system. As BCAAs are important biomarkers of some diseases, these results showed that the developed method could be a potential diagnostic tool in clinical research.

A novel thin, wood-based carbon material with heterogeneous pores, film of lignocellulosic carbon material (FLCM), was successfully fabricated by carbonizing softwood samples of Picea jezoensis (Jezo spruce). Simultaneous increase in the specific surface area of FLCM and its affinity for electrolyte solvents in an electric double-layer capacitor (EDLC) were achieved by the vacuum ultraviolet/ozone (VUV/O-3) treatment. This treatment increased the specific surface area of FLCM by 50% over that of original FLCM. The results obtained in this study confirmed that FLCM is an appropriate self-supporting EDLC electrode material without any warps and cracks. (C) 2013 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.

This paper presents a microfluidic system for the active and precise control of microdroplet division in a micro device. Using two horizontal pneumatic valves formed at downstream of bifurcating microchannel, flow resistances of downstream channels were variably controlled. With the resistance control, volumetric ratio of downstream flows was changed and water-in-oil microdroplets were divided into two daughter droplets of different volume corresponding to the ratio. The microfluidic channels and pneumatic valves were fabricated by single-step soft lithography process of PDMS (polydimethylsiloxane) using SU-8 mold. A wide range control of the daughter droplets' volume ratio was achieved by the simple channel structure. Volumetric ratio between large and small daughter droplets are ranged from 1 to 70, and the smallest droplet volume of 14 pL was obtained. The proposed microfluidic device is applicable for precise and high throughput droplet based digital synthesis.

In this study, we fabricated a microfluidic organic light emitting diode (OLED) and evaluated its performance. The microchip consisted of a 3 x 3 matrix array of OLED pixels in SU-8 microchannels sandwiched by indium tin oxide (ITO) anode and cathode pairs. Liquid organic semiconductors introduced into the microchannels were employed as the light emitters. Electroluminescence was successfully observed at the emitting area of the microchannels. A current density of 0.298 mA/cm(2) was measured at 70V. In our prototype microfluidic OLED, the patterning of the liquid emitters was confirmed in the microchannels on a single chip. This result shows that the proposed structure can be applicable for liquid-based display. (C) 2013 Elsevier B.V. All rights reserved.

We present an active droplet merging device, which can merge various sizes of micro droplets in different numbers by using pneumatically controlled horizontal PDMS microvalves. The merging part consists of a main and side channels separated by a pillar array. The pillar array structure is contained within a microfuidic channel. The function of the pillar array provides a bypass path to the continuous flow (oil) inside the merging chamber. Droplets are successfully generated within the channel and achieve merging by controlling the selective different numbers and diameters of droplets through varying the flow resistance of main and side channel. In the merging chamber, a droplet will enter and slow down its movement. It will wait and then merge with the sequential droplets. These experiments demonstrate that such a merging device can controllably select and adjust the distance between the different adjacent micro droplets without any generation of sister droplets in the side channel. The device has no desynchronization problems. Thus, it can be applied for efficiently mixing the droplets in various diameters and numbers without changing the structure of the merging chamber. Hence, this device can be a more effective choice when applying microfluidics to chemical and biological applications.

We have succeeded for the first time to quantify biological compounds in human plasma using pillar array columns. A fast and quantitative method for the determination of branched-chain amino acids (BCAAs) in human plasma using pressure-driven liquid chromatography on a chip was developed. BCAAs were firstly derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and then analysis of NBD-BCAAs was optimized to be finished in 100 s. With the help of an internal standard, the concentrations of BCAAs in human plasma samples were quantitatively determined. The developed method should be a useful tool for fast diagnosis in clinical field.

This paper reports a fast separation of biological compounds on pillar array columns with low dispersion and low pressure-drop (LD-LPD) turns using pressure-driven liquid chromatography. We found that a pillar array column with LD-LPD turns is useful for efficient and fast analysis of biological compounds. With high flow rate, one-minute separation of fluorescent derivatives of six amino acids was successfully performed. The analysis time was only one-fifth compared to a corresponding result using a pillar array column in a previous work. This result indicated that one-minute separation of complex mixtures could be realized using pillar array columns with LD-LPD turns. Copyright © (2013) by the Chemical and Biological Microsystems Society All rights reserved. All rights reserved.

We designed and fabricated a droplet division device for a wide range dynamic volume ratio and size control of microdroplets. Water-in-oil microdroplets generated at cross junction were separated using active flow resistance control of a Y-shaped droplet division device. Flow resistance of each outlet channel is controlled by two horizontal pneumatic valves formed at the downstream of the bifurcating microchannel. Available volume ratio of daughter microdroplets ranged from 1:1 to 1:145. Size control from about 9 pi to 1 nl was also realized. The generation rate is constant even if the droplet sizes are different in three digits.

Live-cell imaging of inflammatory cytokine secretion from human monocytes was successfully performed on a microfabricated well array chip by time-resolved fluoroimmunoassay using total internal reflection fluorescence microscopy. The system enabled to monitor secretion activity from tens of cells at a time resolution of 1 min. We first observed the close correlation between the loss of cell membrane integrity and "non-classical secretion" of IL-1β cytokine of inflammasome activated human peripheral monocytes.

Lowerature AuAu bonding was achieved under vacuum ultraviolet irradiation in the presence of oxygen gas (VUV/O3). The Au surfaces obtained after the VUV/O3 treatment were analyzed by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) measurements. The results indicate that the amount of carbon-based contaminants was dramatically decreased and that there was no serious damage to Au surfaces caused by the VUV/O3 treatment. The AuAu bonding temperature was successfully reduced to 150°C after the VUV/ O3 treatment. The average shear strength was approximately 56 MPa, and cross-sectional scanning electron microscopy (SEM) images of the bonded samples confirmed the absence of voids and cracks. Therefore, VUV/O3 treatment is highly effective for achieving lowerature AuAu bonding. © 2013 The Japan Institute of Metals and Materials.

This paper presents a stand-alone microfluidic system composed of a reusable valve control part and a disposable microwell-array-embedded fluidic chip for high throughput cell analysis. The valve control part and the fluidic chip are fabricated separately and combined together in experiments. Since valve control of the device and fluid injection are driven by solenoid actuators and electro-osmosis (EO) micropumps, respectively, access-tube-free system is achieved. Utilization of addressable valve control method makes possible to drive 25 on-chip hydraulic valves by 10 solenoid actuators. The prototype fluidic chip with 16 microwell array and 4 reagent injection ports on top of palm-top size substrate (30 x 40 mm) is fabricated and integrated to make a replacement of multi-kind reagents inside the system. With this system, other functional fluidic networks can be replaced easily. After testing on/off switching performances of on-chip valves, multi-reagent exchange trial is carried out, revealing precise reagent injection of ten-nanoliter order to each microwell. The proposed system also shows high performance of power consumption, realizing introduction of two reagents to 16 microwells with 11.9 Wh. (c) 2012 Elsevier B.V. All rights reserved.

We studied the effects of 172 nm Xe₂* excimer lamp irradiation on polyethylene terephthalate (PET) surfaces. Two kinds of techniques were applied: vacuum ultraviolet (VUV) light irradiation and VUV irradiation in the presence of oxygen gas (VUV/O₃). The modified PET surfaces were investigated by using contact angle measurements which enabled the surface free energy to be calculated, X-ray photoelectron spectroscopy (XPS), nano-thermal analysis (nano-TA), and atomic force microscopy (AFM). The surface free energy increased significantly after the treatments. The results of XPS analysis showed that the elemental ratio of oxygen on the surface increased, whereas that of carbon decreased. From the deconvoluted C1s and O1s spectra, it was revealed that new oxidized functional groups such as alcoholic and carboxyl groups were generated. The nano-TA results showed that a low melting temperature (T_m) layer had formed on the VUV and VUV/O₃ treated PET surfaces. The results of AFM measurements showed there were no remarkable changes after the treatments compared with untreated PET. In summary, the VUV and VUV/O₃ treatments using a Xe₂* excimer lamp not only change the surface functionalities but also reduce the T_m of the PET surfaces without significantly affecting the surface morphologies.

The novelty of this study resides in the fabrication of stoichiometric and stress-reduced Si3N4/SiO2/Si3N4 triple-layer membrane sieves. The membrane sieves were designed to be very flat and thin, mechanically stress-reduced, and stable in their electrical and chemical properties. All insulating materials are deposited stoichiometrically by a low-pressure chemical vapor deposition system. The membranes with a thickness of 0.4 mu m have pores with a diameter of about 1 Am. The device is fabricated on a 6 '' silicon wafer with the semiconductor processes. We utilized the membrane sieves for plasma separations from human whole blood. To enhance the separation ability of blood plasma, an agarose gel matrix was attached to the membrane sieves. We could separate about 1 mu L of blood plasma from 5 mu L of human whole blood. Our device can be used in the cell-based biosensors or analysis systems in analytical chemistry.

Here we describe fast analysis of biomolecules by newly developed pressure-driven liquid chromatography (LC) on a chip with integration of a gradient elution system. We have reported the fabrication of a gradient elution system using a cross-Tesla mixer on a chip with pillar array columns [1]. In this study, we applied the chip to the analysis of biological compounds, and showed that 10 times faster separation was achieved under gradient elution than under isocratic elution. The retention times under gradient elution conditions were corresponded to the values estimated by semi-empirical equation, which showed that the gradient elution system worked validly.

Recent studies of diamond-like carbon (DLC) coated medical devices have indicated possibility for developing biochip applications. We have deposited DLC film on cyclo-olefin polymer (COP) sheet by using radio frequency plasma chemical vapor deposition technique. To enhance the adhesion strength between the COP sheet and the DLC films, the COP surface was modified by oxygen (O-2) or nitrogen (N-2) plasma treatment before the film coating. The critical load of samples was measured by using a scratch test. The result showed the adhesion strength of films was improved by the plasma treatment. After the DLC film coating, we performed the plasma post-treatment of O-2, N-2 or hexafluoroethane (C2F6) gases to control the wettability of the material surface. The wettability, structure, roughness, and chemical composition of the samples have been investigated by a contact angle measurement, Raman spectroscopy (Raman), atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). These measurements indicated that wettability on the surface condition of DLC films was easily controlled by plasma post-treatment of O-2, N-2 and C2F6. Furthermore, results of XPS showed that wettability of the surface condition is strongly dependent on chemical components with existemce of oxygen, nitrogen and flourine. We have estimated the wettability of hydorphilicity and hydrophobicity on DLC coating under plasma post-treatment for biochip applications.

In this study, fabrication of microstructures was carried out using newly developed UV imprinting system named "Roller Press Scan (R)" for large-area replication. Micro lens arrays were replicated using two types of UV resins and molds, onto quartz substrates.
Microstructures have been replicated in uniform and have been confirmed high-throughput productivity.

Continuous nano structures whose sizes 100 nm line and space were successfully fabricated using two step nanoimprint including oxygen (O-2) plasma irradiation on a silicon substrate in 8 X 56 mm(2) area. Silicon substrate surface condition is important property because fine and continuous pattern forming depend on photo curable resin uniform coating. O-2 plasma irradiation is realized to change into hydrophilic without damage for silicon substrate. The water contact angle was decreased to smaller than 40 after O-2 plasma irradiation. Therefore O-2 plasma irradiation has an advantage of treatment process for continuous nanostructure forming. Our activities on UV nanoimprint lithography are expected to be progress for large area continuous nano structures fabrication.

The fluorescence-activated cell sorter instrument has contributed significantly to life sciences. However, this instrument has limitations including the inability to detect and hence sort nanometer-sized particles such as quantum dots (Qdots) and virus particles. Here, a microfluidic device for analyzing and sorting nanometer-sized particles has been developed. To achieve sensitive detection, the sample flow was hydrodynamically sheathed and effectively excited with a focused laser beam. Flow control was performed by a sol-gel transition of a thermoreversible gelation polymer. This flow control approach enabled us to restrict the lateral diffusion of nanometer-sized particles and to sort the particles in ∼10 μm channels. Single Qdots with diameters of ∼10 nm were detected at a linear flow velocity of about 4 mm/s, and the Qdots were successfully sorted with the sorting system. Using the developed sorter in an application, Qdot-labeled actin DNA was separated from unwanted glyceraldehyde-3-phosphate dehydrogenase DNA, and the purity of Qdot-labeled actin DNA increased following the sorting. This study represents the first example of active separation of biomolecules labeled with single 10 nm-sized particles of Qdots. © 2011 Elsevier B.V.

A method to fabricate microstructures that are ideal for optical applications was developed. This method enabled structures with a high aspect ratio to be fabricated from an amorphous perfluorinated polymer, CYTOP, which has an identical refractive index to that of water. Using the method, a microwell array device was developed for the purpose of high-throughput protein quantification. Evaluation of the optical properties of the array using total internal reflection fluorescence (TIRF) microscopy demonstrated that the device did not interfere with TIRF imaging at the bottom of each microwell. This method can expand the possible applications of biophotonic devices as well as TIRF imaging. (C) 2011 Elsevier B.V. All rights reserved.

Low-temperature direct bonding of poly-methylmethacrylate (PMMA) plates was achieved by pre-treatment with vacuum ultraviolet irradiation in the presence of oxygen gas (VUV/O-3), with vacuum ultraviolet irradiation in a nitrogen atmosphere (VUV), or with oxygen plasma. Based on surface analysis by attenuated total reflection Fourier-transform infrared spectrometry (ATR-FT-IR), x-ray photoelectron spectroscopy and near edge x-ray absorption fine structure spectroscopy, chemical changes of the PMMA surface after the pre-treatment were investigated. Changes in morphology and softening point were also investigated by nano-thermal analysis and atomic force microscopy. From the results, the bonding mechanisms proposed are described as follows: during the bonding process, the increased or generated polar groups cause an increase in the dipolar interactions (such as hydrogen bonding) between two pre-treated PMMA surfaces; in the case of VUV/O-3 or VUV pre-treatment, a low-T-g layer is generated on the surface and this layer acts as an adhesive for the direct bonding of layers by diffusion.

In this study, a new wafer bonding method for MEMS (micro electro mechanical systems) packaging is presented. The seal lines of sub-micron size Au particles with a width of 50 mu m were formed on wafers by means of screen-printing. The bonding process was carried out at 300 degrees C under reduced pressure, 1 x 10(-3) mbar. The bonded wafers were diced into 5 mm x 5 mm individual chips. The bond strength of each chips was about 20 MPa measured by a tensile test and about 40 MPa by a shear test in the average. It was confirmed that two wafers were successfully bonded with screen-printed Au particle seal lines. The proposed method can be applied to practical MEMS packaging. (C) 2011 Elsevier B.V. All rights reserved.

A novel system for hydrophilic surface treatment was developed. This system consists of a vapor deposition polymerization (VDP) unit for aromatic polyurea coating and a vacuum ultraviolet (VUV) irradiation unit for the hydrophilic treatment of the coated polyurea. Because the two vacuum chambers are connected by a load-lock system, a highly hydrophilic surface can be obtained without airborne molecular contamination (in situ process). The typical thickness of the polyurea film ranges from tens of nanometers to several micrometers. This system can be used for the high-throughput fabrication of chemical/biochemical microchips, which require a stable highly hydrophilic surface. The polyurea is made highly hydrophilic and a water contact angle of <20 degrees is obtained. The surface free energy measurement and Fourier transform infrared (FT-IR) measurement results show that the degree of hydrophilic treatment is related to the VUV light intensity and the density of O-3 and exited oxygen atoms on the polyurea. (C) 2011 Elsevier B.V. All rights reserved.

We have developed a novel sensor that enables us to measure the relative story displacement of a building structure in real time. This lateral displacement sensor (LDS) is composed of a light-emitting diode (LED) array, which is fixed on the ceiling, and a position-sensitive detector (PSD) unit, which is placed on the floor. We optimized the LDS to achieve high accuracy in lateral displacement measurement. The accuracy was evaluated to be 60 mu m by conducting shaking table tests. Two LDSs were implemented in an actual building equipped with an active variable stiffness (AVS) system, and the building was vibrated with seismic waveforms by an exciter placed on the rooftop. The seismic displacement of the second floor relative to the first floor was measured using the LDS. Furthermore, the inclination angle of the second floor could be measured using the LDS during the seismic vibration. Using the AVS system, we realized the residual displacement of the second floor without inducing damage to the building, and succeeded in real-time residual displacement measurement for the first time. These results indicate that the LDS is useful for the health diagnosis of a building structure. (C) 2011 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

A sequential and high-throughput single-cell manipulation system for a large volume of cells was developed and the successive manipulation for single cell involving single-cell isolation, individual labeling, and individual rupture was realized in a microhydrodynamic flow channel fabricated by using two-dimensional simple flow channels. This microfluidic system consisted of the successive single-cell handlings of single-cell isolation from a large number of cells in cell suspension, labeling each isolated single cell and the lysate extraction from each labeled single cell. This microfluidic system was composed of main channels, cell-trapping pockets, drain channels, and single-cell content collection channels which were fabricated by polydimethylsiloxane. We demonstrated two kinds of prototypes for sequential single-cell manipulations, one was equipped with 16 single-cell isolation pockets in microchannel and the other was constructed of 512 single-cell isolation pockets. In this study, we demonstrated high-throughput and high-volume single-cell isolation with 512 pocket type device. The total number of isolated single cells in each isolation pocket from the cell suspension at a time was 426 for the cell line of African green monkey kidney, COS-1, and 360 for the rat primary brown preadipocytes, BAT. All isolated cells were stained with fluorescence dye injected into the same microchannel successfully. In addition, the extraction and collection of the cell contents was demonstrated using isolated stained COS-1 cells. The cell contents extracted from each captured cell were individually collected within each collection channel by local hydrodynamic flow. The sequential trapping, labeling, and content extraction with 512 pocket type devices realized high-throughput single-cell manipulations for innovative single-cell handling, feasible staining, and accurate cell rupture. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3567101]

A real-time secretion monitoring assay from living single-cells was realized by total internal reflection fluorescence imaging with an optically optimized microwell array chip fabricated of an amorphous fluoropolymer, CYTOP on the basis of a fluorescence sandwich immunoassay. After individual mast cells were stimulated with lipopolysaccharide in the microwell array, their proinflammatory responses were monitored as cytokine secretion along time. mRNA levels of cytokines by single-cell quantitative PCR was also measured after the secretion assay. The results showed that each of stimulated mast cells is quantitatively and qualitatively distinguishable from each other in terms of cytokine secretion and their mRNA profile. Copyright © (2011) by the Chemical and Biological Microsystems Society.

Real time assay of protein secretion from living single cells was realized by coupling total internal reflection fluorescence (TIRF) microscopy observation and an optically optimized microwell array device. This system was based on a sandwich immunosorbent assay. Individual cells were cultured on an inverted microscope in microwell arrays fabricated of an amorphous fluoropolymer, CYTOP, to be monitored by TIRF imaging. CYTOP have no interference for the TIRF imaging because the refractive index of CYTOP is almost same as that of water. Using this system, we could succeed in real time secretion assay of lipopolysaccharide stimulated mast cells and the secretion time course of IL-1β from a single MC/9 cell was obtained successfully. © 2011 IEEE.

Low-temperature direct bonding of two cyclo-olefin polymer (COP) plates is realized by pretreatments of vacuum ultraviolet (VUV) light irradiation, VUV irradiation in the presence of oxygen gas (VUV/O-3), or oxygen plasma treatment. The bond strength was strong enough to observe bulk destruction on the fractured surfaces after the tensile test of the sample. To investigate the mechanism underlying the low-temperature direct bonding, attenuated total reflection Fourier-transform infrared spectrometer (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS), contact angle measurements, and atomic force microscopy (AFM) surface analysis methods were carried out for the treated COP samples. These experimental results showed that polar functional groups (e.g., -OH, -COOH) are generated by each treatment. These groups are expected to generate dipolar interactions including hydrogen bonds on the surfaces of the pretreated COPs at room temperature. In case of VUV and VUV/O-3 treatments, degradation of COP was also occurred and the degradation layer acted as an adhesive for the direct bonding. Thermal annealing enhances creation of strong covalent bonds (-C-O-C-) changed from hydrogen bonds. (c) 2010 Elsevier B.V. All rights reserved.

In this paper, we present the filtration of a liquid sample from polystyrene microparticles analogous to the separation of a biological liquid from mixed particles such as whole blood. The proposed self-tuning of flow resistance can prevent the excessive clogging of microparticles in the microfilter by allowing the automatic change of the flow direction when the microfilter is clogged. Numerically, at about 80% of the clogging of microparticles in the pillar channel, the sample flow is regulated suddenly to the bypass channel. Experimentally, the clogging behavior at the five successive pillar channels and the self-tuning of flow are compared by measuring the clogging area and volume with time. Also, the microfilter array connected in a series can provide an increase in the sample volume proportionally without excessive pressure build-up. This implies the potential to reduce cell fracture in the filtration of biological cells. (C) 2011 The Japan Society of Applied Physics

We fabricated novel flexible capacitive tactile sensors that can detect both the direction and distribution of an applied force. The sensor consists of a conductive silicone rubber as a movable electrode and fixed electrodes formed on a poly(ethylene terephthalate) (PET) film with silver paste. The dimensions of sensor head are 10.4 x 10.4 x 0.8mm(3). We developed the tactile sensor using screen-printing techniques and atmospheric-pressure plasma pretreatments. We experimentally evaluated the tactile responses to the applied force. The sensor detected the input force-distribution with a force ranging up to 10N. The flexible thin PET film substrate enables fitting to the tight space and curved surface, and this capacitive tactile sensor is applicable for low-cost controllers of cellular phones and personal computers. (C) 2011 The Japan Society of Applied Physics

This paper describes a post-UV curing process, called anti-sticking curing process (ACP), for fluorinated polymer (NIF) molds. After fabrication by UV imprinting, an NIF mold was irradiated by a strong UV light. The results of surface free-energy calculations, X-ray photoelectron spectroscopy (XPS), and Vickers hardness measurements showed that the surface state of NIF can be described as follows: active functional groups in the photosensitive radical initiator remained on the surface of the NIF mold after UV imprinting. After ACP, these active groups were consumed by further UV polymerization, and the fluorinated components moved to the surface. Thus, an improvement in the releasability of NIF molds is expected.

We propose a novel sensor system for monitoring the structural health of a building. The system optically measures the relative-story displacement during earthquakes for detecting any deformations of building elements. The sensor unit is composed of three position sensitive detectors (PSDs) and lenses capable of measuring the relative-story displacement precisely, even if the PSD unit was inclined in response to the seismic vibration. For verification, laboratory tests were carried out using an X theta-stage and a shaking table. The static experiment verified that the sensor could measure the local inclination angle as well as the lateral displacement. The dynamic experiment revealed that the accuracy of the sensor was 150 mu m in the relative-displacement measurement and 100 mu rad in the inclination angle measurement. These results indicate that the proposed sensor system has sufficient accuracy for the measurement of relative-story displacement in response to the seismic vibration.

This paper presents a new strategy for sorting fluorescently labeled cells with a microfluidic device Cell separation was performed with flow switching using changes in fluidic resistance in a waste channel caused by sot-gel transition of a thermo-reversible gelation polymer (TGP) The TGP is liquid at room temperatuie and turns into a gel state upon heating The sol-gel transition of the TGP was Induced by heating with a 1480 nm laser light for about 3 ms. When a fluorescence signal emitted from a target particle was detected, the waste channel is heated with the laser to increase the flow resistance of the channel This permits the target particles to be sorted and transferred to the collection channel In contrast to a previously reported TGP-based sorter, the sample sorted using the microfluidic cell sorter of the present study does not have to be mixed with TGP solution. and the sorted sample is suitable for following experiment. The performance of the cell sorter was evaluated by separating fluorescent microspheres Two kinds of fluorescent microspheres were separated with a recovery ratio and purity of about 90% As an application of the cell sorter, Escherichia coli cells expressing the green fluorescent protein (GFP) were separated from those expressing the Discoma sp red fluorescent protein (DsRed) About 17,000 cells were sorted with a 75% recovery ratio and 90% purity at a throughput of about 5 cells/s. (C) 2010 Elsevier B.V. All rights reseived

This paper focuses on the effects of a vacuum ultraviolet (VUV) surface treatment process on the interconnections for flip chip and 3-D integration. Organic contaminants that hinder reliable bonding are broken down and eliminated from the bumps and pad surfaces by irradiation with UV light at a wavelength of 172 nm at room temperature. There is no charge buildup, no temperature increase, and no ion bombardment damage during the process. Two different VUV cleaning conditions, with N(2) or O(2) gas in the vacuum chamber, were compared and evaluated. Samples of flip chip with Cu/Sn bumps and Au surface substrate were examined by measurement of contact angle, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and atomic force microscopy (AFM) before and after VUV surface treatment. Cleaning times and ambient conditions have dramatic effects on the surface contact angles. The photoelectron spectra of C 1s were obtained by XPS analysis for information on the chemical species and the XPS results showed a reduction in surface carbon for both Au and Cu/Sn after the cleaning. The evidence indicates cleavage of the carbon-carbon bonds in the organic molecules occurs during the cleaning process. From the shear test results, it appears that VUV treatment improves the Cu/Sn-bump bonding strength, making it two times larger than for untreated samples. No delamination or obvious voids were detected on the bonding interface by Scanning acoustic microscopy (SAM) and cross-sectional SEM analysis. The experiments show that the VUV cleaning can effectively remove the organic contaminants on the surface of the bonding pads and improve the bonding strength.

An approach to control the diameter of high-aspect-ratio pores formed into a silicon wafer by an electrochemical etching process is reported. Hole (h(+)) was involved in the etching reaction and the collection of the h(+) was the key factor. Artificial micro-cavities were fabricated on the silicon surface prior to the etching. The depth of the space charge region (SCR), Schottky barrier on the silicon-electrolyte interface, was adjusted regarding the depth of the micro-cavities by applied overpotential and specific resistance of the silicon wafer. The collection of h at the tip of the cavity site was widely controlled by the adjusted SCR. Consequently the electrochemically etched domain at the cavity site was actively tuned, and then high-aspect-ratio pore with the controlled diameter was formed. The diameter was tuned by the SCR depth which was controlled by the overpotential and the specific resistance. The diameter tuning mechanism worked under the mask-free condition. (C) 2010 Elsevier B.V. All rights reserved.

This paper describes the fabrication process of CoPt nandot arrays on a glass disk substrate with a CoZrNb underlayer as a soft magnetic underlayer (SUL) by using an electrochemical process, and also the analysis on the magnetic properties of these fabricated CoPt nanodot arrays. We formed nano-patterned substrates by UV-nanoimprint lithography (UV-NIL) on the glass disk substrate. CoPt was electrodeposited into the nano-patterned substrates optimizing the electrodeposition condition and bath composition as well as a Cu intermediate layer. The construction of the nanodot arrays were CoPt nanodot arrays (20 nm)/Cu (5 nm)/CoZrNb (100 nm)/Cr (5 nm)/Glass disk. Magnetic signals were clearly observed on the dc magnetized state and multi domain were observed in each nanodot on the ac magnetized state by magnetic force microscopy (MFM). The perpendicular coercivity of the CoPt nanodot arrays was 430 kA/m. These results showed electrochemical process can be used for the manufacture of magnetic recording media.

We propose a novel sensor for directly measuring the relative displacement of a building structure. The sensor is composed of a laser light source and a phototransistor (PT) at-ray. The PT array is immobilized on the floor together with a photo scattering plate made of glass, whereas the laser light source is separately immobilized on the ceiling. The photo scattering plate is placed in front of the PT array and distributes the laser beam oil the multiple PTs. The relative displacement between the ceiling and the floor is estimated by the distribution of the PT output voltages, and the displacement is estimated with a resolution finer than the interval between the PTs. The accuracy of the relative displacement sensor (RDS) is experimentally assessed by conducting a shaking table test exhibiting several waves from harmonic sinusoidal waves to real seismic waves. We discuss the feasibility of real-time monitoring system utilizing this sensor. (C) 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

In this study, we show for the first time that the separation efficiency of a pillar array column under pressure-driven liquid chromatography (LC) conditions can be improved using a separation channel with low-dispersion turns. The pillar array column was fabricated by reactive ion etching of a silicon substrate. With the low-dispersion-turn geometry, a column with a length and width of 110 mm and 400 mu m, respectively, could be fabricated on a 20 x 20 mm microchip. Under nonretained conditions, the solute bands obtained for fluorescent compounds remained almost unchanged even after passing through the low-dispersion turns; however, significant skewing of the solute bands was observed in the case of constant-radius turns. Two coumarin dyes were well resolved under reversed-phase conditions, and a maximum theoretical plate number of 8000 was obtained. Successful separation of the fluorescent derivatives of six amino acids was achieved in 140 s. These results indicated that the separation efficiency of microchip chromatography could be significantly improved using a long separation channel with low-dispersion turns.

Selective droplet sampling system which can deliver target droplets to five different chambers is realized by pneumatically controlled horizontal PDMS microvalves. One inlet and five outlets sorting are performed by only two pneumatic valves using the high aspect ratio flexible parallel PDMS wall structures. Selective droplets sampling is obtained with outlet flow resistance control by deformable horizontal microvalves and walls. The proposed simple flow control structure enables total flow system with simple fabrication by a single PDMS molding. The sampling was performed within 1 second under pneumatic pressure from 0 kPa to 250 kPa.

We have developed a novel surface treatment process using vacuum ultraviolet (VUV) light with a wavelength of 172 nm and formic acid vapor. A previous study showed that the VUV process can help remove the organic contaminants on the bonding surfaces and improve the shear strength [1]. This new work focuses on studying the effects of VUV/O3 and formic acid treatments. The formic acid (HCOOH) vapor removes the metal oxides from the surfaces before the bonding process. Evaporated Cu/Sn and immersion Au were used for the bonding micro-bumps and bonding pads in our evaluations. Different cleaning conditions with VUV/O3, formic acid vapor, or both were compared and evaluated. X-ray Photoelectron Spectroscopy (XPS) was used to study the surface elemental composition of the micro-bumps and pad surfaces before and after the cleaning process. The photoelectron spectra of Cls, Sn3d, and Au4f were obtained with XPS. The XPS results showed the atomic carbon concentrations were significantly decreased by the VUV/O3 treatment process, while the Sn and Au concentrations were increased by the VUV/O3 and formic acid treatment because of the removal of the organic contaminants and metal oxides from the surfaces. The bonding strength of the Cu/Sn bumps was evaluated using a shear test tool. The results shows that the combination of VUV/O 3 and formic acid treatment obtains the highest average shear strength among the treatments tested, with a shear strength almost 2.5 times stronger than the untreated samples. © 2010 Materials Research Society.

We studied the feasibility of using vacuum ultraviolet (VUV) treatment as a surface improvement technique with Au-Au flip-chip bonding. For fine-pitch electrical interconnections in three-dimensional (3D) stack applications, robust and reliable bonding is desirable; in this case, surface modification treatment is needed before the bonding process. A VUV surface treatment was used to remove organic contaminants. Samples of electroplated Au pads were examined by X-ray photoelectron spectroscopy (XPS) to evaluate the chemical composition of the Au surfaces. The XPS results revealed that the carbon-based contaminants on the surface were removed by the VUV treatment. The shear strength of the bonded sample was also improved. The average shear strength of a bump with VUV treatment is 1.6 times larger than that of a bump without VUV treatment. Cross-sectional scanning electron microscopy (SEM) images of the bonded samples confirmed the absence of voids and cracks. The results show that VUV treatment has clear effects on Au-Au flip-chip bonding. (C) 2010 The Japan Society of Applied Physics

We propose a novel sensor for directly measuring the relative displacement of a building structure. The sensor is composed of a laser light source and a phototransistor (PT) array. The PT array is immobilized on the floor together with a photo scattering plate made of glass, whereas the laser light source is separately immobilized on the ceiling. The photo scattering plate is placed in front of the PT array and distributes the laser beam on the multiple PTs. The relative displacement between the ceiling and the floor is estimated by the distribution of the PT output voltages, and the displacement is estimated with a resolution finer than the interval between the PTs. The accuracy of the relative displacement sensor (RDS) is experimentally assessed by conducting a shaking table test exhibiting several waves from harmonic sinusoidal waves to real seismic waves. We discuss the feasibility of real-time monitoring system utilizing this sensor. © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley &amp
Sons, Inc.

Microfluidic systems have significant implications in the field of cell separation since they could provide platforms with inexpensive, disposable and sterile structures. Here, we present a novel strategy to integrate microfluidic sorters into a single chip for high throughput sorting. Our parallel sorter consists of a microfluidic chip with a three-dimensional channel network that utilizes flow switching by a heat-induced sol-gel transition of thermoreversible gelation polymer. The 8 parallel sheathed sample flows were realized by injecting sample and buffer solutions into only 2 inlets. The sheathed flows enabled disposal of unwanted sample waste without laser irradiation, and collection of wanted sample upon irradiation. As an application of the sorter, two kinds of fluorescent microspheres were separated with recovery ratio and purity of 70% or 90% at throughputs of about 100 or 20 particles per second, respectively. Next, Escherichia coli cells expressing green fluorescent protein were separated from those expressing DsRed with recovery ratio and purity of 90% at a throughput of about 20 cells per second.

A novel low-temperature bonding method was developed by using polyurea film as intermediate layers. A microchip with a microchannel having a highly hydrophilic surface was realized by pretreatment with vacuum ultraviolet light irradiation under an oxygen atmosphere (VUV/O(3)). The bonding temperature is low enough to use thermo-plastic channel plates such as PMMA (poly(methyl methacrylate)) with negligible deformation of the channel structure. The results of contact angle measurements indicate the highly hydrophilic surface of the microchannel was retained after the bonding process. There was no leakage or obstacles to smooth fluidic flow at the bonded interface. For actual micro-biochip fabrication with this method, the post-hydrophilic treatment after bonding process is unnecessary. (C) 2008 Elsevier B.V. All rights reserved.

Gas encapsulant, about 1.4 nl volume, generation was performed by using a simple gas-organic-water multiphase junction. Polystyrene microcapsules containing gas of 140 μm in diameter were generated 40 capsules/sec averagely. Long time gas sealing was realized with polystyrene film of about 100 nm in thickness. Also, the droplets' size and gas amount could be controlled by flow rate control. © 2009 CBMS.

Parallel and sequential manipulation of trapping, labeling and content extraction of single cell was realized using a 2-D simple flow channels. The proposed system consists of main channels, cell trapping pockets, drain channels and single cell content collection channels. We fabricated prototypes having 16 cell trapping pockets and 512 cell trapping pockets. Sequential all single cell handling for COS-1 cell was confirmed in 16 pockets type [1]. The sequential trapping and labeling were achieved in 512 pockets type. Capture rate for COS-1 cell was 83.2% and that for BAT cell was 70.3%. These devices are useful for high throughput single cell analysis. ©2009 IEEE.

This paper presents a microscale benefit of a secondary flow obtained in a curved rectangular microchannel, which is generally unfavorable and negligible in conventional fluid flow. We have demonstrated the separation and sorting of micro beads by their size using secondary flow. The physical mechanism occurring in the size-selective separation was explained based on the numerical analysis of the characteristic velocity distribution on the cross-sectional plane normal to the main flow stream. The dynamic trajectories of micro beads of different sizes and materials are visualized and compared for the experimental demonstration. We also discuss the effects of both the shape uniformity of the micro beads and the inlet condition on the size-selective separation.

A fabrication method of uniform gratings on composite semiconductors using ultraviolet nanoimprint lithography (UV-NIL) is described. Since the grating pattern was batch transferred to the resin on substrates in this process, a high throughput fabrication process is expected. Both the dry etching process and the wet etching process can be performed for composite semiconductors patterning. The uniformity of the pattern height on a 3 inch GaAs substrate is better than the standard deviation of 2.6.

The microfluidic platform is an important tool for diagnosis and biomedical studies because it enables us to handle precious cells and infectious materials safely. We have developed an on-chip microfluidic sorter with fluorescence spectrum detection and multiway separation. The fluorescence spectrum of specimens (495-685 nm) in the microchannels was obtained every 2 ms using a 1 x 16 arrayed photomultiplier tube. The specimen was identified by its spectrum and collected into the corresponding channel based on our previously reported thermoreversible gelation polymer technique (Y. Shirasaki, J. Tanaka, H. Makazu, K. Tashiro, S. Shoji, S. Tsukita and T. Funatsu, Anal. Chem., 2006, 78, 695-701). Four kinds of fluorescence microspheres and three kinds of Escherichia coli cells, expressing different fluorescent proteins, were successfully separated with accuracy and purity better than 90% at a throughput of about one particle per second.

Desktop type equipment of thermal-assisted UV roller imprinting was developed. A remarkable advantage of the desktop type equipment is expected to be easy evaluation of replication results using different molds with small amounts of resin. Replication tests were carried out under various scanning speed of the stage, UV intensity, and roll temperature. Pattern replication was improved by heating roll under the same scanning speed of stage. Heating of the roll was effective to realize better pattern replication under the same scanning speed of the stage.

A novel cyclo-olefin polymer (COP) microchip was developed integrated with an electrospray ionization (ESI) emitter tip for microchip electrophoretic separation and mass spectrometric detection. The microchip was fabricated by hot embossing and low-temperature direct bonding. The ESI emitter tip structure was formed directly at the microchip electrophoresis (MCE) outlet. Since these microchips enable negligible dead volume at the electrospray port, efficient spray of the sample necessary for acceptable resolution mass spectrometry (MS) was realized. Stable spray was also achieved at the low flow rate (similar to 0.1 mu L/min) without additional pump. By applying the fabricated COP chip to the MCE-ESI-MS analysis, successful separation and detection of caffeine and arginine was achieved. (c) 2007 Elsevier B.V. All rights reserved.

We present fabrication methods of functional three-dimensional (3-D) micromesh structures coated with titanium dioxide (TiO(2)) microparticles and biocatalysts. The 3-D micromesh structures are useful for fabricating highly efficient microreactors because of their large surface area. In this study, TiO(2)-embedded SU-8 micromesh structures were formed by coating a TiO(2)/SU-8 mixture onto the surface of SU-8 micromesh structures. Biocatalyst-immobilized micromesh structures were also formed by coating a biocatalyst/photopolymer mixture onto SU-8 micromesh structures.

This paper describes the continuous and uniform organic encapsulated micro-bubble generation system in a water flow microchannel including a lumped gas and organic injection junction. The micro-bubble was formed by the blow of organic phase into a water phase in microchannel and the gas was encapsulated in the thin organic membrane. Multiphase microchemical systems provide the large interfacial area, fast mixing and fast reaction efficiency to achieve increased performance in microfluidic system. The diameter and thickness of organic microbubble were well controlled by the flow rates of water phase and organic phase. The diameter of the gas bubble encapsulated organic membrane was ranged from 110 mu m to 220 mu m, while the thickness of organic membrane from 4 mu m to 16 mu m. The generation rate of organic micro-bubble was 40 numbers per second with the uniform volume controllable, ranging from 214 pL, to 855 pL. The organic membrane is applicative for the chemical reaction media, and the organic bubble is expected to apply as capsules of reactive gas handling in microfluidic system. (C) 2007 Elsevier B.V. All rights reserved.

Antireflection nanostructures for GaN light-emitting diodes (LEDs) were fabricated by reactive ion etching (RIE) using Ni as an etching mask. The Ni mask was formed by electrodeposition in combination with ultraviolet nanoimprint lithography (UV-NIL). The antireflection nanostructures of 600 nm in depth, 300 nm in diameter, and 500 nm in pitch were fabricated on a GaN substrate. The radiant intensity of the LEDs was increased 1.5 times compared to that of a conventional LED. Since this method enables the fabrication of wafer-level GaN nanostructures with a low cost process, it is applicable to the fabrication of photonic crystals.

A Magnetic nanodots array fabrication method using ultraviolet nanoimprint lithography (UV-NIL) and electrodeposition was developed. Since the photocurable resin patterned by UV-NIL was directly used for electrodeposition mask, simple and high throughput fabrication process was realized. The CoPt nanodots (diameter: 120 nm) array was formed after the electrodeposition. After chemical mechanical polishing (CMP), the arithmetic mean roughness (R(a)) of the track area was smaller than 1 nm..

A parallel and passive (without any actuators or electrodes) cell distribution method for a cellular diagnostic microwell array was developed. This method can be used to simultaneously distribute cells evenly to arrayed microwells only by introducing Cell suspensions into the inlet. To regulate the dispersion of the number of distributed cells into each microwell, we conceived a novel concept, the self-regulating pinched flow. The self-regulating pinched flow is realized in a functional microchannel, which consists of center micropillar colonnades and side channels. Computational fluid dynamics (CFD) simulations were carried out to optimize the design of the pinching area. We developed a prototype device that can be used to Successfully distribute the beads uniformly in eight parallel microwells. The coefficient of variation (CV) of the distributed beads in the microwells was 29.3%.

We have fabricated a 50-μm-wide and a 30-μm-deep microchannel device by hot embossing and the direct bonding of poly(methyl methacrylate) (PMMA) plates with dimensions of $20\times 20\times 1$ mm3 and evaluated the device's mechanical, optical, and fluidic characteristics. The device's bond strength was confirmed to be sufficiently high for practical use as well as for withstanding severe cleaning conditions, such as ultrasonic cleaning in deionized water. The optical loss around the bonded interface was also evaluated, and no increase in light absorption was observed. There was no leakage or obstacles to smooth fluidic flow when methylene blue test liquid flowed in the channel. The above results confirmed that the hot embossing and direct bonding technologies for microchannel manufacturing using PMMA plates can realize high-performance microchannel devices.

A low-temperature, direct bonding method for poly(methyl methacrylate) (PMMA) plates has been developed by employing surface treatment by atmospheric pressure oxygen plasma, vacuum oxygen plasma, ultraviolet (UV)/ozone or vacuum ultraviolet (VUV)/ozone. Reasonable bonding strength, as evaluated by a tensile test, was achieved below the glass transition temperature (T,). The highest bonding strength among the achieved results is 1.43 MPa (about three times the value for conventional direct bonding) at an annealing temperature of 50 degrees C and an applied pressure of 2.5 MPa for 10 min. Low-temperature bonding prevents deformation of the PMMA microstructure. A prototype PMMA microchip that has fine channels of 5 pm depth was fabricated by hot-embossing using a Si mold. After atmospheric pressure oxygen plasma activation, direct bonding was carried out at an annealing temperature of 75 degrees C and an applied pressure of 3 MPa for 3 min. The method gives Good bonding characteristics without deformation and leakage. This low-temperature bonding technology can be applied to polymer micro/nano structures. (c) 2007 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

Nanoscale dot patterns of cobalt alloy were formed on a silicon substrate using the ultra-violet nanoimprint lithography (UV-NIL) technology in combination with an electrodeposition process. We developed an improved UV-NIL equipment that can evacuate the chamber during imprinting. Using this equipment, we successfully imprinted 240-nm dot patterns with 500 nm pitch on a photocurable resin with high dimensional accuracy. Thickness control of the resin and imprinting under vacuum are important issues to obtain fine nanopatterns. Using these resin patterns as a mask layer, 300-nm cobalt alloy patterns are successfully formed by the electrodeposition process. (c) 2007 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

This paper details a three-dimensional sheath flow sorting microsystem for separation and collection of biomolecules. High-speed particle and biomolecule 3D sheath flow sorting system was realized using reversible thermosensitive hydrogel. The sol-gel transfer of the thermosensitive hydrogel generated by focused IR laser irradiation performs flow switching, the response time of the sol-gel transformation using Mebiol Gel (TM) was less than 1 ms. For actual bio-applications, accurate and high-speed micro sorter is realized by optimizing the channel structure and by utilizing 3D sheath flow. High-speed sorting less than 3.0 ms from detection to separation of targets and no error sorting for 45 min (100,000 counts) in 3D sheath flow sorting system was realized. 3D sheath flow can be focused to 1.2 mu m of transverse distribution and 6.0 mu m of longitudinal distribution in regard to microbeads of sample flow. The same flow velocity and flow line of the focused sample flow are kept at constant laser irradiation time and power to sort the target. Since sorting was performed in simple and disposable PDMS-glass microchannels without any electric stimulation and mechanical valve structures, the proposed system is suitable for many biochemical applications. (C) 2006 Elsevier B.V. All rights reserved.

Multiple core-sheath liquid transfer for continuous fiber synthesis was realized using matrix arrangement of 3D sheath flows. Each sample could be focused less than 30Pm in diameter. The matrix array of the sample flow was achieved by the combination of horizontal and vertical configuration of the separated sheath flows. In this work, 4-sample sheath flows were achieved successfully. This method will be applicable to fabricate multi-component nano/microfibers and tubes.

Nanostructure fabrication process using ultraviolet nanoimprint lithography (UV-NIL) and electrodeposition were proposed. This method shows remarkable advantages in high throughput production and fabrication cost. For this process, the newly resin which endures wet process was developed. Co dot arrays of 220nm were fabricated by electrodeposition after UV-NIL. GaN structure of 300nm was also realized using Ni as an etching mask fabricated by proposed process.

Two types of high-speed particle and biomolecule sheath flow sorters were realized using thermosensitive hydrogel. One is all hydrogel sheath flow and the other is two-phase sheath flow that consists of a water flow including samples and two hydrogel carrier flows; these have been utilized instead of the air and water droplet two-phase flow used in the conventional commercialized cell sorting system. Flow switching is performed by the sol-gel transfer of the thermosensitive hydrogel generated by focused infrared (IR) laser irradiation. High-speed sorting less than 5.0 ms and no error sorting (120 000 counts) in the all hydrogel sheath flow system while 20 ms in the two-phase sheath flow was realized. Since sorting was performed in simple PDMS-glass microchannels without any electric stimulation and mechanical valve structures, the proposed system is suitable for many biochemical applications.

This paper describes the fabrication method of an all SU-8 microfluidic device with built-in 3D fine micromesh structures. 3D micromesh structures were seamlessly integrated into the SU-8 sealed microchannel. To eliminate gap formation and filling of the microchannel, the built-in micromeshes in the microchannel were formed by photolithography after bonding the SU-8 top-cover layer and the SU-8 bottom substrate. The lift-off method, using lift-off resist as a sacrificial layer, was utilized to release the all SU-8 microfluidic chips. Monolithic SU-8 structures realize uniform physical and chemical surface properties required in microfluidic devices for practical use. As an application, fragmentation of a water droplet in an organic carrier formed by a two-phase flow was demonstrated.

In this work, we present an extended gate field effect transistor (EGFET)-based biosensor integrated with a silicon micro-fluidic channel for the electronic detection of streptavidin-biotin protein complexes. The connection between the EGFET and microfluidic system could be achieved with the proposed device, as it offers isolation between the device and solution, compatibility with the integrated circuit (IQ technology and, is applicable to the micro total analysis system (mu-TAS). The device was fabricated on the basis of semiconductor IC fabrication and micro-electro mechanical system (MEMS) technology. Au was used as the extended gate metal to form a self-assembled monolayer (SAM) with thiol. The bindings of the SAM, streptavidin and biotin were detected by measuring the electrical characteristics of the FET device. We also verified the interactions among the SAM, streptavidin, and biotin by using surface plasmon resonance (SPR) measurements. Furthermore, atomic force microscopy (AFM) images of the bio-layers formed on the Au electrode were taken in a solution in order to determine the presence of protein biomolecules with the proposed configuration. (c) 2006 Elsevier B.V. All rights reserved.

High-efficientcy micro-electrochemical devices are realized by increasing electrode surface areas while maintaining keeping chip size. The use of three dimensional (3-D) electrodes instead of planar electrodes is effective for this purpose. To realize a metal pattern on 3-D structures, spray coating was utilized and the optimum condition for achieving a good photoresist step coverage was determined. A good step coverage of the photoresist was obtained on the obtuse corner formed by the anisotropic wet etching of (100) silicon and even on the vertical corner formed,by deep reactive ion etching (RIE). We applied this method to fabricate a high-performance micro direct methanol fuel cell (mu DMFC). An open circuit voltage of 548 mV and a maximum power density of 0.72 mW/cm(2) were obtained at room temperature with 2 M methanol.

Micro droplet generation is one of the basic functions in a micro total analysis system (micro TAS). Micro TAS has a lot of advantages and thus has wide range of applications in these days. In this study, a numerical calculation code for micro multi-phase flow is developed using Moving Particle Semi-implicit (MPS) method. Since surface tension is extremely strong and dominant in micro multi-phase flow, a time step is divided to sub-time steps for the surface tension term. This sub-time step algorithm enables us to calculate micro multi-phase flow efficiently with keeping numerical stability. Micro droplet generation in a micro channel is analyzed by the present code in two dimensions. The calculated droplet size, pitch and production rate show good agreement with those of the experiment.

We developed a novel biological cell injection method for a large number of diagnostic wells fabricated in parallel. This method facilitates simultaneous cell injection into a microwell array with a simple channel configuration, which can distribute cells evenly to each microwell only by introducing cell suspensions from the inlet. In order to enhance the uniformity of the numbers of injected cells in each microwell, we developed the new concept of flow interchange, which can suppress deviation of the cell flow profile in the cell loading channels. The uniformity of the injected fluorescent beads in each microwell was evaluated using prototype devices of eight microwell arrays. It was confirmed that the flow interchange structure is effective to realize uniform injection. The coefficient of variation of bead numbers in eight microwells was 20.7%.

In this article, the development of a novel technique to fabricate spherical polymeric microcapsules by utilizing microfluidic technology is presented. Atom transfer radical polymerization (ATRP) was employed to synthesize well-defined amphiphilic block copolymers. An organic polymer solution was constrained to adopt the spherical droplets in a continuous water phase at a T-junction microchannel, and the generation of the droplets was studied quantitatively. The flow conditions of two immiscible solutions were adjusted for the successful generation of the polymer droplets. The morphology of the microcapsules was examined. The efficiency of these polymer microcapsules as containers for the storage and controlled release of loaded molecules was evaluated by encapsulating the microcapsules with Congo-red dye and investigating the release performance using temperature controlled UV-VIS spectroscopy.

This paper presents the inclined UV lithography in water medium and 3D mixing microchannel application. The theoretical limit of the inclination angle of the structure is determined by the difference of the refractive index between air and SU-8. In order to reduce the mismatch of the refractive index between air and photoresist, DI water was used as exposure medium instead of air. As a result, the maximum angle of the inclined structure was improved from 38.7 degrees (in air) to 56.2 degrees (in water). Fine and high aspect ratio SU-8 structures were obtained using UV exposure in water medium. As a microfluidic application, a microchannel having 3D slanted grooves was designed and fabricated. 45 degrees slanted grooves were formed successfully on the sidewalls of the microchannel by using inclined UV exposure in water medium. Mixing efficiency of this microchannel was evaluated by CFD simulation and cross-sectional fluorescence image detection using confocal microscope. (c) 2005 Elsevier B.V. All rights reserved.

We have developed a microfabricated fluorescence-activated cell sorter system using a thermoreversible gelation polymer (TGP) as a switching valve. The glass sorter chip has Y-shaped microchannels with one inlet and two outlets. A biological specimen containing fluorescently labeled cells is mixed with a solution containing a thermoreversible sol-gel polymer. The mixed solution is then introduced into the sorter chip through the inlet. The sol-gel transformation was locally induced by site-directed infrared laser irradiation to plug one of the outlets. The fluorescently labeled target cells were detected with sensitive fluorescence microscopy. In the absence of a fluorescence signal, the collection channel is plugged through laser irradiation of the TGP and the specimens are directed to the waste channel. Upon detection of a fluorescence signal from the target cells, the laser beam is then used to plug the waste channel, allowing the fluorescent cells to be channeled into the collection reservoir. The response time of the sol-gel transformation was 3 ms, and a flow switching time of 120 ms was achieved. Using this system, we have demonstrated the sorting of fluorescent microspheres and Escherichia coli cells expressing fluorescent proteins. These cells were found to be viable after extraction from the sorting system, indicating no damage to the cells.

A novel flow type electrochemical immuno sensing system using 3-D comb electrodes, which enables high-speed enzyme immunoassay on a single microchip, has been developed. A trap-and-release system of magnetic beads and a sheath flow sorting system are integrated on the chip. The integrated system realizes repeatable sample preparation and sensing. Using this system, AFP detection in the range from 25ng/mL to 500ng/mL was obtained within 30 minutes. This system can be applied widely for high sensitive enzyme immunoassays.

Fabrication process for picoliter volume SiO2 glass tube array partially embedded in Si wafer was developed. As a template for the glass tubes, macropore array was formed at the surface of n-Si(1 0 0) wafer by photo-assisted electrochemical etching process. The area-selective formation of the array was achieved by applying Au/Cr micropatterns formed at the back-side surface of the substrate as the shade mask, which controls the illumination condition to optimize the etching reaction conditions. Subsequently, surface of the macropores was wet-thermally oxidized to form glass layer, and the bulk Si region was removed by alkaline etching, remaining the "glass tubes". As a result of complete removal of the bulk Si, released glass tubes were obtained. By partial removal of the bulk Si part, the glass tubes were exposed, fixed in the remaining Si substrate in the form of well-ordered array. It was confirmed that the depth, the exposed region and the wall thickness of each glass tube were controllable by adjusting the parameters such as the duration of the Si electrochemical etching, the alkaline etching and the wet-thermal oxidation, respectively. In order to demonstrate microreaction in the glass tube, aqueous rhodamine B solution was injected into the tubes and excitation light was irradiated to them. As a result, the fluorescence of rhodamine B was clearly detected, confirming the applicability of the glass tubes for various kinds of devices and systems such as microreactors. (C) 2005 Elsevier Ltd. All rights reserved.

To realize highly sensitive electrochemical immunoassays, a micro-fabricated three-dimensional (313) electrode was fabricated and applied to enzyme immuno assay based on production of a redox species. The dimensions of the electrodes are 10 mu m in width and 30 mu m in height, with 20 mu m spacing in between, and the 30 pairs of anode and cathode electrodes made up a single sensor. This structure lead to enhancement of the electrochemical reaction, nearly 100% of trap ratio of redox species. It can be applied to highly sensitive enzyme immuno sensing based on p-aminophenylphosphate (PAPP). Applicability of this technique to the immuno assay for one of the clinical diagnostic marker proteins (alpha-fetoprotein; AFP) from 6 to 500 ng/mL was demonstrated. (c) 2004 Elsevier B.V. All rights reserved.

This paper presents functional three-dimensional microchannels whose top and side walls have slanted microgrooves. These microchannels can generate short pitch spiral flow for efficient chaotic mixing. We proposed a novel fabrication method for 3-D SU-8 molds using two-step inclined backside exposures and additional two-step top side exposures. The width and depth of the SU-8 microchannel are 100 mu m. Slanted grooves of 50 mu m in width and 30 mu m in depth were patterned on the top and the side walls of the microchannel. Their orientation angle was 63.5 degrees with the microchannel axis. It was demonstrated that the microchannel with slanted grooves on three walls achieved short pitch spiral flow compared to the microchannel with slanted grooves on one wall. Since liquid in the channel flows along the grooves on the walls, optimum design of the pitch and placement of the slanted grooves enables efficient spiral flows in the channel. (c) 2004 Elsevier B.V. All rights reserved.

An X-ray microcalorimeter is a high performance X-ray spectrometer that can achieve both high energy resolution of conventional wavelength dispersive spectrometers (WDS) and high quantum efficiency of energy dispersive spectrometers (EDS). The energy resolution can be theoretically improved to about 1 eV, which value is 120 times better than that of conventional Si(Li) spectrometers and nearly 100% of quantum efficiency can be achieved using microabsorbers. In order to realize high energy-resolution X-ray imaging using an array of X-ray microcalorimeters, two types of 2 x 2 X-ray microcalorimeter arrays were fabricated and tested. Using an X-ray microabsorber so-called "mushroom-shaped" X-ray microabsorber, the filling factor was enhanced to about 70%. We tested Sn and Bi as an X-ray microabsorber. Consequently, the Sn absorber degrades the energy resolution because of the long time constant. This problem was cleared using the Bi microabsorber. The achievable energy resolution was also investigated. As a result, the energy resolution of 6.3 eV was obtained with the test device. (C) 2004 Elsevier B.V. All rights reserved.

A micro chamber integrated with an extremely low dead volume sample injector for real-time monitoring of living cell was developed. By means of the combination of isotropic etching and deep trench etching using CCP-RIE and ICP-RIE, the sample injector with negligible dead volume of less than 0.05 nl is realized. Using fabricated devices, the reproducible sample injection of the order of 1 nl was obtained. Biological cell culture of rat mast cell was also performed in the fabricated micro chamber. (C) 2003 Elsevier B.V. All rights reserved.

A design for a novel micro direct methanol fuel cell (mu-DMFC) of 0.018 cm(2) active area is described. The mu-DMFC was prepared using a series of fabrication steps from micro-machined silicon wafer including photolithography, deep reactive ion etching, and electron beam deposition. The novelty of this structure is that we have fabricated the anodic and cathodic micro-channels arranged in plane, dissimilar to the conventional bipolar structure. The first objective of the experimental trials was to verify the feasibility of this novel structure on basis of MEMS technology. Preliminary testing results show that this new concept L-DMFC generates electricity. (C) 2004 Elsevier B.V. All rights reserved.

Microscale Bi electrodeposition process was developed to fabricate the array of mushroom-shaped absorbers for the high sensitive X-ray imaging sensor, so called X-ray microcalorimeter array. The bath composition and operating conditions for Bi electrodeposition was optimized, and sufficient bath stability and surface smoothness of the deposits were achieved by applying the additives such as diethylenetriamine pentaacetic acid and sodium n-dodecyl sulfate with appropriate concentration. By applying the two-step exposure steps for the "stem" part and the "roof" part, the mold to deposit the mushroom-shaped microstructure was formed from single-layered photoresist coating. The absorber array was successfully fabricated by the sequential processes of Bi electrodeposition into the mold, precise polishing, and mold removal.

This paper presents a fabrication method of in-channel three-dimensional micromesh structures using conventional photolithography. The micromesh was realized by exposing UV light from the backside of the SU-8 coated metal-patterned glass substrate for different angles. Number of exposures and irradiation angles decided the shape and the size of micromesh. Based on this technique, three different micromesh-inserted microchannel structures were fabricated using the same Cr pattern on the glass substrate. For hydrodynamic characterization, their flow resistances were measured. Finally, for the application of micro total analysis systems (muTAS), the microfilter was fabricated and its filtering property was demonstrated. (C) 2003 Elsevier B.V. All rights reserved.

This paper presents a sheath flow multiple sample injector that realizes concentration-conservative sample injection. Stepwise flow is used to reduce the dilution of the sample reagent. Based on the CFD simulation results, it is estimated that sample reagent is diluted to 94% in a conventional sample injector. With stepwise flow, however, the level of dilution is reduced and the average concentration is estimated to be near 100%. For the experiment evaluation, a sample injector is fabricated and the sample injection using stepwise flow is visualized using a fluorescent measuring system. The accuracy of the injected sample volume and the feasibility of multiple sample injection are evaluated based on the experiment results. (C) 2003 Elsevier B.V. All rights reserved.

We have developed multi-pixel TES microcalorimeters in order to realize high-energy resolution and X-ray imaging. A Sn absorber and a Bi absorber were formed on Si3N4 and SiO2 membrane using two-step exposure photolithography and electrodeposition. A FEM analysis was carried out to investigate the performance of the X-ray microabsorbers. In addition, a superconducting through-wafer interconnection was demonstrated considering the future X-ray imager using microcalorimeters. Detail of the fabrication techniques, characteristics and simulation results of two types of the microabsorbers, as well as those of the calorimeters are described. (C) 2003 Elsevier B.V. All rights reserved.

Sn electrodeposition was employed for fabricating an array of microabsorbers with a 'mushroom-shaped' microstructure for a precision X-ray microdetector, the so called X-ray microcalorimeter. A deposition process for flat and smooth Sn films, which was suitable for the use of the absorber material, was developed by optimizing the conditions of additives such as o-cresol-4-sulfonic acid and polyethyleneglycol (PEG) to the Sn bath. The Sn films exhibited suitable properties, i.e. a higher superconducting transition temperature than the operating temperature of the X-ray microcalorimeter. The mushroom-shaped absorber array was successfully fabricated by Sn electrodeposition in combination with a photolithographic technique. (C) 2002 Elsevier Science B.V. All rights reserved.

The flow-induced vibration of the microcantilever is investigated. In particular, to avoid flow disturbance resulting from size of measuring probe, we use the monolithic boron-doped piezoresistive microsensors. By characterizing the dynamic behavior of the microcantilever, the new micromechanics is experimentally determined, completely different from the conventional mechanics in the flow-induced vibration. © 2003, The Institute of Electrical Engineers of Japan. All rights reserved.

High performance flow monitoring systems are needed to monitor the particles and biomolecules flow in micro channels. For the design of microfluidic devices and systems, the finite element analysis tools play an important role. These systems are useful to evaluate the correspondence between the computational fluid dynamics (CFD) simulation and the actual flow in micro channels. The micro flow cell realizing 3D sheath flow was designed and the prototype was fabricated and evaluated. Since the flow distribution of the sample is critically changed with the pressure and the flow rate of the carrier, the 3D CFD analysis is indispensable to design the micro flow cell. The principle of 3D sheath flow is applicable to realize particles and biomolecules observation and handling systems. Novel micro flow switches using thermal gelation of methylcellulose (MC) have been developed. Since the local plug is formed illuminating the laser beam, the flow can be stopped at any point in the microchannels. The switching time of about 1 sec both open-to-close and close-to-open was achieved. By using the MC as a carrier flow, DNA, protein and biological cell sorting micro flow systems can be realized in the simple 2D microchannel structures. © 2003 Elsevier B.V. All rights reserved.

A novel automatic biomolecules sorter using thermal gelation of methyl cellulose (MC) solution was realized. In our previous work, we already reported the sol-gel transformation of MC could be used for the flow switch. The flow switch was applied for the prototype of the particles handling system with manual control. The sorting time in this case was about 2 seconds. However the time of sol-gel transformation was estimated within a second. To achieve faster sorting speed, we fabricated a PC controlled sorting system consisting of an automatic fluorescence sample detector, focused IR laser source, and two galvano mirrors for switching and scanning of the laser. As a result the sorting time was reduced to around 100 msec.

For the next generation of astronomical X-ray imaging detectors, arrays with large numbers of microstructures (similar to1000 pixels) will be required. To meet this requirement, a tin absorber for an X-ray microcalorimeter, which has a so-called "mushroom" shape, is fabricated by electrodeposition and polishing. This method enables the fabrication of a large number of arrayed microcalorimeters. Details of the fabrication process, the characteristics of the absorber and the fabricated microcalorimeters are reported.

In order to apply SiO2-SiO2 bonding with hydrofluoric acid (KF bonding) for micro-electro-mechanical systems (MEMS) fabrication, the optimal bonding conditions were examined under different temperature, HF concentration and bonding time. The necessary HF concentration and the necessary time for bonding are reduced by elevating the bonding temperature. The time for bonding was reduced from 24 h at room temperature to 30 min at 80 degrees C, 60 min at 60 degrees C under the conditions of 0.5 wt.% HF concentration and 1.3 MPa applied pressure. The bonding time is comparable to that of anodic bonding. Reliability of the HF bonding was confirmed by the results of temperature cyclic tests and thermal shock tests. A long term stability of the bonded sample was also evaluated by helium (He) leak detection. The measured He leak rate was less than 2.0 X 10(-9) atm cm(3)/s which is much smaller than that calculated value through component materials of the sample. A novel quartz UV detection micro Row cell for chemical analysis having Si shade structure was fabricated by the HF bonding. The absorbance unit for UV absorption detection of the cell was improved remarkably. (C) 2000 Elsevier Science S.A. All rights reserved.

Studies on SiO2-SiO2 bonding with hydrofluoric acid (HF) are described. This method has a remarkable feature that bonding can beobtained at room temperature. Advantages of this method are low thermal damage, low residual stress and simplicity of the bonding process, which are expected for the packaging and assembly of micro-electro-mechanical systems (MEMS). The bond characteristics were measured under different bonding conditions of HF concentration, applied pressure, another chemicals for bonding and so on, The bond strength depends on the applied pressure during bonding. To achieve reliable bonding, HF concentration of higher than 0.5 wt.% and a large applied pressure of 1.3 MPa are required. The bonding is also observed using KOH solution in stead of HF. Transmission electron microscopy (TEM), secondary ion mass spectrometry (SIMS), radioactive isotope (RI) analysis and electron probe micro analysis (EPMA) were applied to evaluate the bonded interface. The results of these analysis indicated that an interlayer of a silicon oxide complex including hydrogen and fluorine atoms is formed between bonded SiO2 to SiO2. The thickness of the interlayer depends strongly on the applied pressure during bonding. Large bond strength is obtained when the interlayer is thin. The bonding mechanism is expected when the SiO2 at both surfaces is dissolved in HF solution, and that the interlayer, which is a binding layer, is formed between substrates by resolidification of dissolved silicon dioxide. Formation of the interlayer plays very important roles for the characteristics of HF-bonding. (C) 2000 Elsevier Science S.A. All rights reserved.

Microbiochemical reactors having two inlet ports and one outlet port were fabricated on a silicon wafer by means of anisotropic etching in order to develop a parallel and automatic experimental system for cell-free translation. Using cell-free extract prepared from Escherichia coli, we tested the reactor for the translation of polyuridylic acid and MS2 phage RNA, and found that polypeptide and protein syntheses could be proceeded according to the genetic codes on the mRNAs. It indicates that the microfabricated reactor is useful for enzymatic reactions including complicated ones like cell-free translation. We also discuss the possibility of microsystems as advanced experimental tools for not only cell-free translation but also other various biochemical and biological research fields.

A very low-power consumption wireless system for monitoring ECG (ElectroCardioGram) is proposed. It consists of ECG detector/transmitter located on the chest and the relay transmitter placed at the wrist. Between the detector part and relay transmitter, the signal is send as the AC micro current flown through the tissue of the body. Since this method obtains very low-power signal transmission of about 8μW(400mVRMS × 20μARMS), the system can be driven by very small power source like a thin film battery. The similar wireless transmission method can be applied for other medical signal/data sensing micro systems sharing the same relay transmitter.