Hitachi-High-Technologies Corporation

Hitachi, Ltd.

Hitachi High-Tech Corporation

Roche Diagnostics Operations, Inc.

Hitachi Chemical Company, Ltd.

Toshiro Saito

Kazumichi Imai

Koshin Hamasaki

Masatoshi Narahara

Kyoko Imai

Takayuki Obara

Haruo Akahoshi

Satoshi Takahashi

Muneo Maeshima

Naoshi Itabashi

Hiroshi Yoshida

Ryuji Tao

Shigeo Suzuki

Yoshiaki Sugimura

Hiroyuki Uchiyama

Sukekazu Aratani

Hans-Peter Josel

Ryoji Inaba

Masahiko Ando

Noriyuki Kinjo

Hiroaki Nakagawa

Takeyuki Itabashi

Akira Kageyama

Kenta Imai

Yoshimitsu Yanagawa

Tsuneaki Kawanishi

Masato Isogai

Katuo Sugawara

Itaru Yanagi

Yasuhiko Tada

Akira Maekawa

Takuya Matsui

Jiro Yamamoto

Yasuo Katsuya

Akira Hosoya

Eri Tarasawa

Kiyoyuki Kagii

Kazuhito Rokutan

Hiroyuki Tomita

Giovanni Valenti

Alessandra Zanut

Massimo Marcaccio

Francesco Paolucci

An analysis method includes: an inflow process of a solution containing a test object, a magnetic support on the surface of which a complex including an antibody labeled with a luminescent agent and recognizes the test object is formed, and a reaction aid to assist reaction of the luminescent agent in a flow cell; a process of capturing the magnetic support over a working electrode by a magnetic field; a process of making the luminescent agent illuminate by applying a voltage to the working electrode; and a process of measuring an amount of luminescence of the luminescent agent. The luminescent process includes: luminescence from action of a first neutral radical, produced from the reaction aid through a cation radical; and luminescence from action of a second neutral radical, produced not through a cation radical, on the luminescent agent. This increases the luminous efficiency of ECL and enhances detection sensitivity.

Biomolecular analysis method and biomolecular analyzer

Paramagnetic fine particles of 1 micron or less used under a strong magnetic field were shown to form beads-like aggregates along the magnetic flux, and become irregularly shaped as such a mass of particles combines with a flat particle layer. This phenomenon becomes a factor that degrades the quality of quantification in bioanalysis. By confining a solution of microscopic magnetic fine particles between flat substrates of high wettability as thin a vertical thickness as possible and attracting the magnetic fine particles under a magnetic field applied from the side of one of the flat substrates, the magnetic fine particles can be evenly immobilized in the form of a film on the substrate surface in a dispersion state, and the quality of the biomolecule quantification can be improved.

Bioanalysis device and biomolecule analyzer

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.

Method and apparatus for nucleic acid analysis

Biomolecules are specifically captured with magnetic particles and the biomolecules are labeled with fluorescence. A magnetic field generator, for attracting the magnetic particles to the support substrate, is provided on the reverse face of the support substrate, and an adhesion layer is provided on the surface of the support substrate to hold the magnetic particles. First, a dispersing solution for the magnetic particles is placed on the surface of the support substrate with the magnetic field in an off state. Next, the magnetic field is turned on, and the magnetic particles in solution are attracted to the support substrate surface. The magnetic particles colliding with the support substrate adhere to the adhesion layer of the support substrate surface, and then the magnetic field is turned off. Thus, aggregations can be broken up while the magnetic particles are held, and a magnetic particle layer on the support substrate can be a single layer.

Analysis device and analysis method

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.

Nucleic acid analysis device and nucleic acid analyzer

An object of the present invention is to provide a highly sensitive immunoanalysis method and analysis apparatus. The invention relates to an analysis method and an analysis apparatus which are constituted in such a way that a component to be measured is reacted with capture component specifically reacting thereto and the reactant is labeled when the component to be measured is present and which are characterized by analyzing the component to be measured with single-molecule sensitivity and resolution by arranging the labeled reactant in a spatially separated certain position and detecting the label of the labeled reactant.

Immunoanalysis method and immunoanalysis device

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.

Method for analyzing biomolecules and biomolecule analyzer

The present invention is intended to provide a method and a device for detecting a biomolecule with high sensitivity and high throughput over a wide dynamic range without requiring concentration adjustments of a sample in advance. The present invention specifically binds charge carriers to a detection target biomolecule, and detects the detection target biomolecule one by one by measuring a current change that occurs as the conjugate of the biomolecule and the charge carriers passes through a micropore. High-throughput detection of a biomolecule sample is possible with an array of detectors.

Biomolecule detection method, biomolecule detection device and analysis device

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.

Method and substrate for nucleic acid amplification, and method and apparatus for nucleic acid analysis

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 10nucleic acid fragments per square millimeter.

Nucleic acid analysis device, method for producing same, and nucleic acid analyzer

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.

Microparticle having single-molecule nucleic acid probe, method for producing same, method for analyzing nucleic acid using same, device for nucleic acid analysis, and apparatus for analyzing nucleic acid

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 (), the nucleic acid having been immobilized on the microparticles () on the substrate () is detected. The microparticles (), which carry the nucleic acid to be detected having been immobilized thereon, are arranged by microstructures () aligned on the substrate ().

Nucleic acid analyzer, reaction device for nucleic acid analysis and substrate of reaction device for nucleic acid analysis

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.

Biomolecule fixing board and method of manufacturing the same

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.

Nucleic acid analysis device and nucleic acid analyzer using the same

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.

Nucleic acid analyzing device and nucleic acid analyzer

Growing community of inventors

Hitachinaka, Japan

Toshiro Saito