Design of an optical linear-discriminant filter: optimization for enhancement of filter transmittance and discrimination accuracy.

To discriminate fine concave and convex defects on a dielectric substrate, an optical machine learning system is proposed. This system comprises an optical linear-discriminant filter (OLDF) that performs linear discriminant analysis (LDA) of the scattered-wave distribution from target samples. However, the filter output from the OLDF is considerably weak and cannot be measured experimentally. Therefore, an algorithm is also proposed to improve the discrimination accuracy and filter transmittance. The designed filter is validated using a rigorous optical simulator based on vector diffraction theory. We also analyze and discuss a mechanism that provides high transmittance with high discrimination accuracy.

Development of a clinical microarray system for genetic analysis screening.

Objectives: Research on the relationship between diseases and genes and the advancement of genetic analysis technologies have made genetic testing in medical care possible. There are various methods for genetic testing, including PCR-based methods and next-generation sequencing; however, screening tests in clinical laboratories are becoming more diverse; therefore, novel measurement systems and equipment are required to meet the needs of each situation. In this study, we aimed to develop a novel microarray-based genetic analysis system that uses a Peltier element to overcome the issues of conventional microarrays, such as the long measurement time and high cost. Methods: We constructed a microarray system to detect the UDP-glucuronosyltransferase gene polymorphisms UGT1A1*6 and UGT1A1*28 in patients eligible for irinotecan hydrochloride treatment for use in clinical laboratories. To evaluate the performance of the system, the hybridization temperature and reaction time were determined, and the results were compared with those obtained using a conventional hybridization oven. Results: The hybridization temperature reached its target in 1/27th of the time required by the conventional system. We assessed 111 human clinical samples and found that our results agreed with those obtained using existing methods. The total time for the newly developed device was reduced by 85 min compared to that for existing methods, as the automated DNA microarray eliminates the time that existing methods spend on manual operation. Conclusions: The surface treatment technology used in our system enables high-density and strong DNA fixation, allowing the construction of a measurement system suitable for clinical applications.

Inverse scattering algorithm for profile reconstruction of a buried defect beneath a dielectric rough surface based on the domain-boundary integral hybrid method.

A reconstruction algorithm for the defect profile beneath a dielectric rough surface using scattered far fields is proposed. This is a fundamental technique for optical measurements, such as diffraction tomography, for defect inspection of microfabricated devices. In general, the profile reconstruction process is considerably time consuming. We propose a domain-boundary integral hybrid method to reduce the number of operations while maintaining the rigor of scattering; the polarization properties, scattering, and multiscattering in the sample are considered. We present reconstruction simulations to validate the proposed algorithm. The reconstruction limit as well as its dependency on sample illumination and rough surface shape are also discussed.

Design of an optical linear discriminant filter for classification of subwavelength concave and convex defects on dielectric substrates.

Identification of the defect type on substrate materials is essential for enhancing their yield ratio. We propose a novel optical filter to discriminate between subwavelength-order concave and convex defects on flat surfaces. This filter performs Fisher's linear discriminant analysis using light wave diffraction. The defect type is discriminated by simply comparing the irradiance at an observation point with the threshold value. Neither the defect image nor phase data, nor a large amount of data processing by a computer, is necessary. Numerical discrimination simulations indicate a discrimination error of 0.85%, and the noise tolerance of the proposed system is also discussed.

Profile reconstruction of a local defect in a groove structure and the theoretical limit under the vector diffraction theory.

The profile of a fine local defect in a periodic surface relief structure is reconstructed from a scattered wave. This defect cannot be imaged with an optical imaging system owing to the diffraction limit, and complicated multiscattering among the high-aspect-ratio grooves and the defect makes it difficult to reconstruct the profile using the scalar diffraction theory. We propose and numerically demonstrate a reconstruction algorithm by applying an efficient vector analysis method-the difference-field boundary element method. We also classify the profile according to the difficulty of reconstruction, which depends on the observation system and the noise level. Finally, this analysis provides the accuracy and limit of reconstruction under the vector diffraction theory.

Field-stitching boundary element method for accurate and rapid vectorial diffraction analysis of large-sized one-dimensional diffractive optical elements.

We propose a field-stitching boundary element method (FSBEM) for diffraction analyses for large diffractive optical elements (DOEs). A field stitching (FS) method separately computes the divided sections of a large DOE and provides the field distribution without field mismatching. However, a divided section must be largely overlapped, which is not efficient in terms of computational resources. In the FSBEM, in addition to spatial division, the electromagnetic field is computed for each component-the reflected, difference, and stitching fields-for rapid convergence of the solution. We validate the FSBEM by computing a one-dimensional DOE and evaluating the convergence property. The sample structure is also computed by the conventional FS method, and the advantages of the FSBEM are discussed.

Fast actual-size vectorial simulation of concave diffraction gratings with structural randomness.

In this study, an actual-size concave grating with structural randomness is numerically analyzed. Numerical electromagnetic analyses that solve Maxwell's equations can provide rigorous diffracted fields including the polarization characteristics. However, because of high computational costs, actual-size gratings with no periodicity have seldom been analyzed. We apply the difference-field boundary element method (DFBEM) for the analyses of actual-size concave gratings with 10,000 random blazed grooves. The DFBEM provides vectorial diffracted or scattered waves with very low computational resources. First, we estimate the accuracy of the computation results, and then we show some relations between the degree of randomness and the diffraction efficiency, including the polarization dependency.

Expansion of the difference-field boundary element method for numerical analyses of various local defects in periodic surface-relief structures.

We expand the difference-field boundary element method (DFBEM) to calculate wave scattering from a variety of local periodic structure defects. The DFBEM is a numerical method for simulating the diffraction caused by a periodic surface-relief structure with a defect. Although it is more efficient than conventional techniques such as the finite-difference time-domain (FDTD) method, the original DFBEM is limited to projection defects. Here, we derive the integral equations and expressions for crack and buried-pillar defects, and also demonstrate some numerical analyses, validating the results by comparison with results from the FDTD method and the dielectric interface boundary conditions.

Design of ultra-compact triplexer with function-expansion based topology optimization.

In this paper, in order to optimize wavelength selective photonic devices using the function-expansion-based topology optimization method, several expansion functions are considered and the influence on the optimized structure based on each expansion function was investigated. Although the Fourier series is conventionally used in the function-expansion-based method, the optimized structure sometimes has a complicated refractive index distribution. Therefore, we employed a sampling function and a pyramid function to obtain a simpler structure through the optimal design. A triplexer was designed by using our method, and the comparison between the optimized structures based on the three expansion functions was also discussed in detail.

Forensic validation of the modified ABO genotyping method using a DNA chip.

ABO typing is effective in several forensic investigations, including the identification of unknown cadavers. When the serological method cannot be used because of the decomposition of ABH antigens, ABO genotyping of DNA is often performed. Previously, we reported a novel ABO genotyping method using a DNA chip as a proof of concept. This chip can simultaneously detect single nucleotide polymorphisms in the ABO gene and a part of the primate-specific D17Z1 sequence for human identification. In the present study, this method was modified and further validated for forensic use. We demonstrated that the modified method can correctly perform ABO genotyping and human identification if the appropriate amount of template (>0.5ng of DNA) is analyzed. Moreover, it was found that this chip method can be used to type highly degraded DNA. This method is expected to be a useful supplemental tool for the identification of individuals from highly decomposed samples.

A novel method for ABO genotyping using a DNA chip.

ABO genotyping is often performed to identify the blood type of decomposed samples, which is difficult to be determined by a serological test. In this study, we developed a simple method for ABO genotyping using a DNA chip. In this method, polymerase chain reaction-amplified and fluorescent-labeled fragments in the ABO gene and primate-specific D17Z1 were hybridized with DNA probes on a chip designed to detect single nucleotide polymorphisms (SNPs) in the ABO gene and part of the D17Z1 sequence. Using blood samples from 42 volunteers and 10 animal species, we investigated whether the chip could be used to detect SNPs in the ABO gene and the D17Z1 sequence. This method was then applied to various forensic samples, and it was confirmed that this method was suitable for the simultaneous analyses of ABO genotyping and species identification. This method fulfills the recent need for the development of rapid and convenient methods for criminal investigations.

Identification of cell surface marker candidates on SV-T2 cells using DNA microarray on DLC-coated glass.

We analyzed gene expression profiles of normal mouse fibroblast BALB/c 3T3 cells and its SV40 transformant SV-T2 cells using our originally developed cell surface marker DNA microarray, which is prepared on a diamond-like carbon-coated glass. As a result, CD62L and IL-6 receptor alpha gene expressions were upregulated in SV-T2 and were thought to be candidates for call surface markers of the cells. The result of microarray analysis was validated by real-time quantitative PCR immunohistochemistry and biological assays. These data show that our cell surface marker DNA microarray should be useful in finding the candidates of cell type-specific surface markers.

Pseudoreticulocytosis in a patient with hemoglobin Köln due to autofluorescent erythrocytes enumerated as reticulocytes by the Cell-Dyn 4000.

Pseudoreticulocytosis in a 25-year-old female patient with hemoglobin Köln is reported. The abnormal hemoglobin, hemoglobin Köln (beta chain, Val98-->Met), had previously been confirmed in the patient at the age of 21 years, as well as in her mother, by polymerase chain reaction-based direct sequence analysis of the beta globin gene. The patient underwent splenectomy at the age of 22 years. On her admission to our hospital for treatment of an immunoglobulin A nephropathy, an analysis by an automated hematology analyzer, the Abbott Cell-Dyn 4000 (CD4000), reported a marked reticulocytosis. Staining by the Brecher method with new methylene blue indicated a moderate reticulocytosis (5.7%) of a lesser extent than that indicated by the CD4000 (51.1%). The frequencies of red blood cells (RBC) with Pappenheimer bodies (13.8%), Heinz bodies (32.7%), and Howell-Jolly bodies (0.3%) were increased. The CD4000 detects RBC with RNA fluorescently stained with CD4K530 as reticulocytes. Autofluorescence of RBC with hemoglobin Köln, as we demonstrated by flow cytometry and fluorescent microscopy, was considered to have caused the pseudoreticulocytosis on the fully automated reticulocyte enumeration by the CD4000.