Emi Tamechika

Protein recognition on a single graphene oxide surface fixed on a solid support

We study protein recognition on a graphene oxide (GO) surface using a single GO piece fixed on a solid support. The GO surface is modified by newly designed processes using pyrene as a linker to an sp2 domain in the GO, an aptamer for thrombin recognition, and a probe dye for fluorescence detection. In this system, the dye probe fluorescence, which was initially quenched by GO, is recovered when the aptamer recognizes the corresponding protein. We demonstrate the label-free and selective protein recognition for thrombin. The elementary processes of protein recognition are observed directly with a confocal laser scanning microscope and an atomic force microscope using an identical piece of GO. They indicate that proteins are recognized homogeneously on the modified GO surface. We also show that the recognition system can be installed and operated in microchannel devices.

Resolution Improvement Using Auxiliary Pattern Groups in Oblique Illumination Lithography

In this paper we present a new resolution improvement technique for nonperiodic patterns where oblique illumination effects are limited. Since the problems are caused by nonperiodicity, a technique called auxiliary pattern group (APG) is introduced to supplement the periodicity. The effects of the APG are shown by simulation, and parameter dependence is also discussed. Experimental results for oblique illumination with a t-π mask confirm that using APGs improves the resolution and focus latitude.

Terahertz Spectroscopic Imaging of Polymorphic Forms in Pharmaceutical Crystals

A terahertz spectroscopic imaging system was fabricated for the detection of two-dimensional molecular distributions in pharmaceutical tablets based on absorption peaks of intermolecular or intramolecular hydrogen bonds in crystals. The terahertz imaging system consists of a terahertz time-domain spectrometer and a three-dimension translational stage. Using the system, we obtained frequency-dependent terahertz images of famotidine polymorphic forms A and B. An offset subtraction process is useful for detecting the distribution in an inhomogeneous tablet containing a mixture of the two forms. The terahertz imaging technique is a valuable tool for the analysis of polymorphic forms of crystal in inhomogeneous pharmaceutical tablets.

Cooperative suction by vertical capillary array pump for controlling flow profiles of microfluidic sensor chips.

A passive pump consisting of integrated vertical capillaries has been developed for a microfluidic chip as an useful component with an excellent flow volume and flow rate. A fluidic chip built into a passive pump was used by connecting the bottoms of all the capillaries to a top surface consisting of a thin layer channel in the microfluidic chip where the thin layer channel depth was smaller than the capillary radius. As a result the vertical capillaries drew fluid cooperatively rather than independently, thus exerting the maximum suction efficiency at every instance. This meant that a flow rate was realized that exhibited little variation and without any external power or operation. A microfluidic chip built into this passive pump had the ability to achieve a quasi-steady rather than a rapidly decreasing flow rate, which is a universal flow characteristic in an ordinary capillary.

Passive fluidic chip composed of integrated vertical capillary tubes developed for on-site SPR immunoassay analysis targeting real samples.

We have successfully developed a surface plasmon resonance (SPR) measurement system for the on-site immunoassay of real samples. The system is composed of a portable SPR instrument (290 mm(W) × 160 mm(D) × 120 mm(H)) and a microfluidic immunoassay chip (16 mm(W) × 16 mm(D) × 4 mm(H)) that needs no external pump system. An integrated vertical capillary tube functions as a large volume (150 μL) passive pump and a waste reservoir that has sufficient capacity for several refill operations. An immunoassay was carried out that employed the direct injection of a buffer and a test sample in sequence into a microfluidic chip that included 9 antibody bands and 10 reference reagent bands immobilized in the flow channel. By subtracting a reliable averaged reference sensorgram from the antibody, we effectively reduced the influence of the non-specific binding, and then our chip successfully detected the specific binding of spiked IgG in non-homogeneous milk. IgG is a model antigen that is certain not to be present in non-homogeneous milk, and non-homogeneous milk is a model of real sample that includes many interfering foreign substances that induce non-specific binding. The direct injection of a real sample with no pretreatment enabled us to complete the entire immunoassay in several minutes. This ease of operation and short measuring time are acceptable for on-site agricultural, environmental and medical testing.

SOI-based photonic crystal line-defect waveguides

We have experimentally demonstrated single-mode light-wave transmission and tunable waveguiding characteristics in photonic crystal (PC) waveguides constructed on a silicon-on-insulator (SOI) substrate as is most likely to be used for the a large scale integration of photonic circuits. Although off-plane diffractive leakage has been a serious problem in SOI-PC waveguides, we have overcome this problem in our narrow line-defect and phase-shifted-hole line-defect waveguide structures. These devices were developed through intensive theoretical studies on PC line-defect waveguieds. We have also demonstrated low-loss mode profile converter that will enable efficient connection between conventional silica-based waveguides and PC line-defect waveguides. The converter features an inversely-tapered silicon wire waveguide with an ultra-thin tip constructed on an SOI substrate. In our experiments, this converter proved capable of coupling loss as low as 0.5dB per conversion. These SOI-based devices represent an important step towards practical large-scale integrated photonic crystal circuits.

Air-band optical resonators in one-dimensional Si photonic crystal waveguides for biosensing applications

Optical cavities using air-band states in Si photonic crystals (PhCs) are proposed as biosensors. Since the light in the air band of PhCs is preferably located at the lower-index cladding rather than the inside of higher-index Si, interactions are enhanced between the light and the target molecules in the cladding, being effective for the sensitive detections. Such an air-band PhC is used as an optical cavity, which is surrounded with another PhC as the photonic-bandgap mirrors. Simulations are performed for air-band resonators in one-dimensional (1D) PhC of arrayed holes in a Si channel waveguide, in order to analyze a figure of sensing, i.e., red shifts in the resonance wavelengths induced by the presence of target molecules. The S value, the amount of red shift caused by the unit change in the cladding index, can be as large as 200 nm/RIU, which is 2 times larger than those for ordinary 1D-PhC resonators. Fabricated devices successfully show the resonance peaks, whose wavelengths and quality factors agree well with theoretical ones. These results suggest that the air-band resonators are promising for high-performance biosensors.

Floating Chip Mounting System Driven by Repulsive Force of Permanent Magnets for Multiple On-Site SPR Immunoassay Measurements

We have developed a measurement chip installation/removal mechanism for a surface plasmon resonance (SPR) immunoassay analysis instrument designed for frequent testing, which requires a rapid and easy technique for changing chips. The key components of the mechanism are refractive index matching gel coated on the rear of the SPR chip and a float that presses the chip down. The refractive index matching gel made it possible to optically couple the chip and the prism of the SPR instrument easily via elastic deformation with no air bubbles. The float has an autonomous attitude control function that keeps the chip parallel in relation to the SPR instrument by employing the repulsive force of permanent magnets between the float and a float guide located in the SPR instrument. This function is realized by balancing the upward elastic force of the gel and the downward force of the float, which experiences a leveling force from the float guide. This system makes it possible to start an SPR measurement immediately after chip installation and to remove the chip immediately after the measurement with a simple and easy method that does not require any fine adjustment. Our sensor chip, which we installed using this mounting system, successfully performed an immunoassay measurement on a model antigen (spiked human-IgG) in a model real sample (non-homogenized milk) that included many kinds of interfering foreign substances without any sample pre-treatment. The ease of the chip installation/removal operation and simple measurement procedure are suitable for frequent on-site agricultural, environmental and medical testing.

Resolution Enhancement by Oblique Illumination Optical Lithography Using a Transmittance-Adjusted Pupil Filter

This paper describes the resolution enhancement by oblique illumination optical lithography using a transmittance-adjusted pupil filter that has a conjugate shape to the secondary light source. The resolution enhancement depends on the amplitude transmittance distribution of the pupil filter in the lens aperture. Thus, the optimum transmittance distribution attaining the highest resolution at a practical depth of focus is investigated, and superior performance is verified experimentally using an actual i-line stepper, that is, the actual resolution improvement is comparable to the simulation results. Despite this improvement, two problems must be addressed. Pattern profiles degrade at the ends of periodical patterns, and the opaque pattern widths of middle-pitch patterns become a little narrow. These two problems are solved by optimizing the transmittance distribution of the filter such that there is no significant deterioration in the high-resolution performance.

A reliable aptamer array prepared by repeating inkjet-spotting toward on-site measurement

A preparation protocol is proposed for a reliable aptamer array utilizing an ink-jet spotter. We accumulated streptavidin and biotinylated-aptamer in this order on a biotinylated-polyethylene glycol-coated gold substrate to prepare an aptamer array. The aptamer array was prepared with an alternate spotting structure where each aptamer spot was placed between reference spots formed with blocking solution thus suppressing contamination from neighboring spots during the blocking and washing processes. Four aptamer spots were prepared in a small area of 1×4.8mm(2) with five reference spots made of blocking solution. We evaluated the thrombin binding ability of the spotted aptamer array using a multi-analysis surface plasmon resonance sensor. We prepared a disposable capillary-driven flow chip designed for on-site measurement (Miura et al., 2010) with our aptamer array and detected thrombin from phosphate-buffered saline at concentrations of 50ngmL(-1) and 1μgmL(-1) (equivalent to 1.35 and 27nM, respectively). A correlation was observed between the refractive index shift and thrombin concentration. This implies that our array preparation protocol meets the requirement for the preparation of a one-time-use chip for on-site measurement.