Abstract: The present invention relates to a method for nucleic acid amplification, which enables clusters of amplified nucleic acid fragments to be sequenced by a sequencer to be formed at a high density and improves throughput of nucleic acid sequence analysis by amplifying the number of nucleic acids in the cluster to 10,000 molecules or more; and a method for nucleic acid amplification for enhancing read accuracy, which achieves a high cluster density and increases the number of the amplified fragments in the cluster by the steps of previously forming a pattern of primer DNAs on a base material and fixing bulky template DNA molecules synthesized from DNA samples thereon to induce amplification reaction.

Abstract: The method for analyzing biomolecules, includes the steps of: immobilizing biomolecules to be analyzed on surfaces of magnetic microparticles; reacting labeled probe molecules with the biomolecules to be analyzed; collecting and immobilizing the microparticles on a support substrate; and measuring a label on the support substrate. Since single-molecule immobilized magnetic microparticles are used in the present invention, the number of biomolecules can be counted, and since hybridization and an antigen-antibody reaction are performed with the microparticles having biomolecules immobilized thereon dispersed, the reaction can be rapidly performed. Further, the type and the abundance of biomolecules of interest can be determined at a single molecular level, so as to evaluate, in particular, the absolute concentration of biomolecules.

Abstract: A convenient method for nucleic acid analysis is provided, which enables 1000 or more types of nucleic acid to be analyzed collectively with high comprehensiveness and with a dynamic range of at least four digits. In particular, provided is a very effective analytical method especially for untranslated RNAs and microRNAs, of which the types of target nucleic acids is 10000 or lower. Nucleic acids can be analyzed conveniently and rapidly with high comprehensiveness and quantitative performance at single-molecule sensitivity and resolution by following the steps of: preparing a group of target nucleic acid fragments one molecule at a time and hybridizing the nucleic acid molecules, which have known base sequences and have been labeled with the fluorescence substances, with the group of the target nucleic acid fragments to detect the fluorescence substances labeling the hybridized nucleic acid molecules.

Abstract: In the conventional nucleic acid analysis devices and nucleic acid analyzers, there was no technique available for sequencing a single nucleic acid molecule easily and highly efficiently. The present invention enabled a highly efficient single molecule immobilization of nucleic acid with good reproductivity in a short time at a low price by providing small metallic bonding pads at predetermined positions on a support substrate, firmly fixing a hydrophobic linker on the bonding pads, and bonding on to the linker bulky microparticles onto which a single molecule of a nucleic acid sample fragment is immobilized. According to the present invention, in the nucleic acid analysis device which uses a nucleic acid analyzer, the nucleotide read length can be extended and many types of nucleic acid molecule to be analyzed can be analyzed at one time.

Abstract: A microparticle having a probe molecule able to capture a specific nucleic acid group to be analyzed is used to extract only the specific nucleic acid group to be analyzed from a nucleic acid sample and the microparticle is thereafter directly immobilized on a smooth plate, whereby a device for nucleic acid analysis is rapidly prepared. Immobilizing a single capture probe molecule onto an individual microparticle in advance and forming, at regular positions on the smooth substrate, an adhesion pad on which a functional group that binds to the microparticle has been introduced makes it possible to readily and rapidly prepare the device for nucleic analysis, where the nucleic acid sample to be analyzed is arranged molecule by molecule in a lattice shape on the smooth substrate.

Abstract: In a nucleic acid analysis device which detects a fluorescent dye on a nucleic acid sample immobilized on a surface of a substrate by exciting the fluorescent dye with an evanescent wave, the detection of a fluorescence signal with a high SN ratio is realized even for a long nucleic acid sample. The nucleic acid analysis device according to the invention is a nucleic acid analysis device in which a plurality of regions for immobilizing a nucleic acid sample are provided on a surface of a support base and a single molecule of a nucleic acid sample is immobilized on at least one of the regions, and which performs sequence determination by performing an extension reaction of the immobilized nucleic acid sample, wherein the immobilization of the single molecule of the nucleic acid sample on the support base is performed at two or more points.

Abstract: Disclosed is a technique for binding microparticles to patterned bonding pads of a metal (e.g., gold) formed on a support. The microparticles each carry a nucleic acid synthetase or DNA probe immobilized thereon for capturing a nucleic acid sample fragment. The technique involves forming, on a support surface, a film having a thickness equivalent to that of the bonding pads; controlling the size of microparticles with respect to the size of bonding pads; and thereby immobilizing microparticles each bearing a single nucleic acid sample fragment to the bonding pads in a one-to-one manner in a grid form. This allows high-density regular alignment and immobilization of many types of nucleic acid fragment samples on a support and enables high-throughput analysis of nucleic acid samples. Typically, immobilization of microparticles at 1-micrometer intervals easily provides a high density of 106 nucleic acid fragments per square millimeter.

Abstract: Provided is a reaction device for nucleic acid analysis wherein microparticles, which carry a nucleic acid to be detected having been immobilized thereon, are aligned in a lattice form on a substrate according to the pixel size of a two-dimensional sensor. By this reaction device for nucleic acid analysis which is provided with a channel-forming reaction chamber on the substrate (101), the nucleic acid having been immobilized on the microparticles (103) on the substrate (101) is detected. The microparticles (103), which carry the nucleic acid to be detected having been immobilized thereon, are arranged by microstructures (102) aligned on the substrate (101).

Abstract: An object of the present invention relates to detecting a target substance with high contrast. The invention relates to analysis of a target substance using a light-transmitting substrate and a metal for inducing plasmon resonance, and further using a low refractive index layer with an opening portion, which forms an interface with the substrate, and which has a lower refractive index than the substrate. Light emitted from a substrate side is totally reflected at the interface to irradiate the metal arranged in the opening portion with evanescent light. Light generated from the target substance by plasmon resonance of the evanescent light is detected. According to the invention, the radiation of evanescent light to a material other than the target substance can be reduced, and thereby light emission from the martial other than the target substance, e.g., a molecule floating around the target substance, can be reduced.

Abstract: This invention provides a biomolecule modifying substrate comprising biomolecules selectively fixed to given regions thereon. The biomolecule modifying substrate comprises: a substrate at least comprising a first surface and a second surface; a first linker molecule comprising a hydrocarbon chain and a functional group capable of selectively binding to the first surface at one end of the hydrocarbon chain, which is bound to the first surface via such functional group; a second linker molecule comprising a reactive group capable of binding to the hydrocarbon chain of the first linker molecule, which is bound to the first linker molecule via a bond between the reactive group and the hydrocarbon chain; and a biomolecule bound thereto via the second linker molecule.

Abstract: The present invention provides a nucleic acid analyzing apparatus which achieves highly accurate analytical ability even in single molecule DNA analysis. The nucleic acid analyzing apparatus detects locations of fluorescent bright spots in image information about light emission, deletes defective bright spots, and thereby creates intensity trace data about proper bright spots.

Abstract: An object of the present invention is to regularly align microparticles, on each of which a nucleic acid synthetase or a DNA probe capable of capturing a nucleic acid sample fragment is immobilized, on a support so as to improve throughput of nucleic acid analysis. The present invention relates to a method comprising immobilizing a nucleic acid synthetase, a DNA probe, or the like in advance to a microparticle, forming a pattern of metal pads each having a diameter smaller than the microparticle diameter with gold or the like on a support, and allowing a microparticle to be bound to the pads via a chemical bond. In addition, when the surfaces of microparticles are electrically charged, a pattern of metal pads each having a diameter equivalent to or larger than the microparticle diameter is formed with gold or the like on a support and a microparticle is allowed to be bound to the pads via a chemical bond.

Abstract: An object of the present invention relates to distinguishing, from a fluorophore of an unreacted substrate, a single fluorophore attached to a nucleotide that is incorporated into a probe by a nucleic acid synthesis. The present invention relates to a nucleic acid analyzing device that analyzes a nucleic acid in sample by fluorescence, wherein a localized surface plasmon is generated by illumination, and a probe for analyzing the nucleic acid in the sample is on the site where the surface plasmon is generated. According to the present invention, since it is possible to efficiently produce fluorescence intensifying effects due to the surface plasmon and to immobilize the probe to a region within the reach of the fluorescence intensifying effects, it becomes possible to measure a nucleic acid synthesis without removing unreacted nucleotide to which fluorophores are attached.

Abstract: An oligonucleotide array comprising an array of multiple oligonucleotides with different base sequences fixed onto known and separate positions on a support substrate, wherein said oligonucleotides are biological stress related genes or complementary sequence chains to the said genes, and the said oligonucleotides are classified according to their gene functions, wherein the fixation region on the support substrate is divided into the said classification.

Abstract: The present invention provides a nucleic acid analyzing apparatus which achieves highly accurate analytical ability even in single molecule DNA analysis. The nucleic acid analyzing apparatus detects locations of fluorescent bright spots in image information about light emission, deletes defective bright spots, and thereby creates intensity trace data about proper bright spots.

Abstract: An object of the present invention relates to detecting a target substance with high contrast. The invention relates to analysis of a target substance using a light-transmitting substrate and a metal for inducing plasmon resonance, and further using a low refractive index layer with an opening portion, which forms an interface with the substrate, and which has a lower refractive index than the substrate. Light emitted from a substrate side is totally reflected at the interface to irradiate the metal arranged in the opening portion with evanescent light. Light generated from the target substance by plasmon resonance of the evanescent light is detected. According to the invention, the radiation of evanescent light to a martial other than the target substance can be reduced, and thereby light emission from the martial other than the target substance, e.g., a molecule floating around the target substance, can be reduced.

Abstract: The present invention relates to a nucleic acid analysis device for analysis of nucleic acid in a sample through fluorometry, in which a localized surface plasmon by light irradiation, and in which a nucleic acid probe or a nucleic acid synthase for the analysis of the nucleic acid in the sample is disposed in a region of generation of the surface plasmon. The present invention allows the fluorescence intensifying effect of the surface plasmon to be produced efficiently and also enables the immobilization of a DNA probe or the nucleic acid synthase in a region on which the fluorescence intensifying effect is exerted, thus making it possible to carry out a measurement on the base elongation reaction without having to remove the unreacted substrate with the fluorescent molecule.

Abstract: This invention relates to a method for diagnosing whether or not a subject suffers from depression in a simple manner with high accuracy using the peripheral whole blood sample of the subject. Specifically, the present invention relates to a method for diagnosing depression comprising the steps of: measuring expression levels of 18 genes selected from the group consisting of FASLG; CX3CR1, TBX21, ID2, SLAMF7, PRSS23, YWHAQ, TARDBP, ADRB2, PPP1R8, MMAA, SQLE, PDHA1, HAVCR2, RACGAP1, AHNAK, EDG8, and DUSP5, in peripheral blood isolated from a subject; and determining whether or not the subject suffers from depression based on the expression levels of the 18 genes.

Abstract: The present invention relates to a method for detecting fusion gene transcripts resulting from chromosomal translocation. Specifically, the method of the present invention comprises allowing at least two or more probes, each of which contains a partial base sequence of exons which sandwich the breakpoint of a fusion gene or complementary base sequence thereof, and each of which immobilized on a support, to hybridize with a sample containing a nucleic acid derived from a fusion gene, thereby allowing the detection of two or more fusion genes at a time.

Abstract: A member useful in a printed wiring board comprises a resin insulating layer, a metallic fine particle or catalyst layer, a metal oxide layer, and a metallic or electroless plating layer, wherein the resin insulating layer contains a resin containing an aromatic amide site such as an epoxy-terminated aromatic polyamide.