Hitachi-high-technologies Corporation

Hitachi, Ltd.

Hitachi Chemical Company, Ltd.

Tsuyoshi Sonehara

Satoshi Takahashi

Tomoyuki Sakai

Takanobu Haga

Takashi Anazawa

Michiru Fujioka

Shuhei Yamamoto

Kunio Harada

Tatemi Ido

Atsushi Takahashi

Kenko Uchida

Hiroshi Kawazoe

Hirokazu Kato

Hiromi Kusaka

Nobutaka Kumazaki

Tomoyuki Kamata

Masao Suga

Masataka Shirai

Chihiro Uematsu

Naoshi Itabashi

Yuji Miyahara

Kyoko Kojima

Akira Fujii

Takashi Irie

Takeshi Ooura

Takuya Matsui

Akimasa Osaka

Chifumi Gouda

The purpose of the present invention is to control, with a simple structure and high accuracy, irradiation of excitation light to a multi-nanopore substrate without interrupting a measurement. Irradiation of excitation light is performed concurrently to at least one nanopore and at least one reference object on a substrate mounted in an observation containerA position irradiated with the excitation light in a measurement sample is calculated on the basis of a signal generated from the reference object detected by a detectorand the measurement and a fixed position control is performed concurrently by performing measurement of the measurement object while a drive control partcontrolling the position of the irradiation of the excitation light to the measurement sample on the basis of the calculation result, whereby an analysis of the measurement sample can be performed in a short time.

Fixed position controller and method

In the microscope observation container according to the present invention, an observed sample is accommodated by an objective lens barrel provided with a housing extending along the radiation direction of excitation light and an objective lens fixed to an inside surface of the housing. The microscope observation container is provided with a structure for collecting a liquid immersion medium added by dispensation, the structure having a portion contacted by the objective lens barrel during observation. During observation the aforementioned portion is contacted by the objective lens barrel, and the liquid immersion medium is thereby sealed by the objective lens barrel and the structure. The aforementioned portion also has an elastic force, and is deformed so as to conform to the housing of the objective lens by the contact.

Microscope observation container and observation device

With a microspectroscopy device provided with an objective lens with a high numerical aperture, a defocus arises from thermal drift, etc., necessitating auto-focusing. Conventional auto-focus based on through-focus image acquisition takes time, and thus, it cannot be applied to continuous measurement over a long time wherein high-speed sampling is carried out. The present invention addresses this problem by having a defocus-sensing beam that has either defocus or astigmatism fall incident on the objective lens. Since how the image of the spot of the beam for defocus sensing blurs differs depending on the orientation of the defocus, real-time detection of the amount and orientation of defocus becomes possible, and high-speed realtime auto-focus becomes possible.

Microspectroscopy device

Provided are a method and an apparatus for easily identifying and detecting fluorescent material types captured in respective reaction regions of a substrate, particularly, a method and an apparatus for identifying and measuring the fluorescence intensities of a plurality of fluorescent materials using a small pixel count. The fluorescence intensities of four or more types of fluorescent materials are divided by a dividing section at ratios different at least for each fluorescence maximum wavelength range, and are detected by at least one detector including pixels for detecting the light fluxes divided at the different ratios. The type of the fluorescent material is determined on the basis of the ratio of the detected fluorescence intensity of the same detection portion, and the fluorescence intensity is measured.

Fluorescence analyzing apparatus and fluorescence detecting apparatus

A fluorescence detector in which a sample substrate is provided with a structure unit comprising a prism or a diffraction grating. After excitation light falling on the sample substrate is totally reflected at a biomolecule-immobilized face that is located in the opposite side of the structure unit, the structure unit allows the emission of the reflected light therefrom. To ensure multiple visual field measurement, a sample substrate-driving unit is provided to scan the sample substrate.

Fluorescence detector

The present invention has an object to provide a method for efficiently detecting an image with a smaller number of pixels. The invention relates to fluorescence analysis which uses a substrate having a plurality of regions for being capable of immobilizing biologically-related molecules in positions of lattice points of a lattice structure, and which causes the fluorescence from a certain lattice point to be wavelength-dispersed in a direction other than the direction toward the adjacent closest lattice point. According to an embodiment, for example, the number of pixels of a two-dimensional sensor required for fluorescence analysis of the regions with the biologically-related molecules immobilized can be set to several hundred times to fifty times smaller than that in the conventional case without degrading the measurement accuracy. This can achieve the improvement of throughput, reduction in price, and/or improvement of the operability of an analyzing device.

Fluorescence analyzing device and fluorescence analyzing method

In order to provide a fluorescence detection apparatus having a high sensitivity, a high processing capacity and a competitive edge in cost, the fluorescence detection apparatus according to this invention irradiate the sample with light so that the aspect ratio of the form of the irradiated region by light on the arrangement surface of the sample may be 1&#xb1;0.1. The preferable form of irradiate region is not limited to one and varies to some extent depending on the item to be optimized. The form of irradiated region may be, for example, a circle, an equilateral triangle, a square, a regular hexagon and the like.

Fluorescence detection apparatus and method, and prism used therein

A metallic structure is provided on a surface of a substrate. A component having a longer wavelength than excitation light is detected from luminescence from fixation positions of biomolecules and emitted from a material other than the biomolecules, and is used for photometrical analysis. As the structure, usable is a particulate (a metallic structure of a size not larger than a wavelength of the excitation light), a minute protrusion, or a thin film with minute apertures, which are made of a metal such as gold, chrome, silver or aluminum. In the case of the particulate or the minute protrusion, photoluminescence of the structure is detected with a biomolecule being fixed thereon. In the case of the thin film with minute apertures, Raman scattered light of specimen solution around the biomolecules, and photoluminescence of the metallic structure near the biomolecules are detected with biomolecules being fixed in the apertures.

Photometric instrument

The object of the present invention is to acquire the brightness of NA&#x3e;1 while alleviating the requirement for the precision of positioning for the collection lens of the sample cell in a non-liquid immersion system. In order to achieve the object mentioned above, the bottom of the sample cell is formed in a curved surface, and an arrangement is made to ensure that the fluorescence irradiated from the focusing point would be parallel pencils when emitted by the cell, and in addition a pinhole is disposed at the focal point of the fluorescence collection lens.

Apparatus for photon detection including a sample cell with an outer surface with a curved bottom, and a pinhole created on a pinhole plate

A fluorescent detection apparatus relates to an analysis technique for qualitatively detecting or quantifying biomolecules by producing an evanescent field on a surface of a substrate, exciting fluorescently labelled biomolecules on the substrate surface in the evanescent field, and detecting the resultant fluorescent light emitted from the biomolecules. The fluorescent detection apparatus has a configuration in which a well is provided in a surface opposing to a sample substrate of a prism, the well is filled with a matching liquid, and the matching liquid is filled between the sample substrate and the prism, thereby improving operability and providing a stable evanescent field.

Fluorescence detection apparatus

An electrophoresis member is produced by laying a plurality of capillaries on an adhesive layer born on a support layer to form a capillary layer, laminating thereon a second support layer, and partially removing the first support layer, the first adhesive layer and the second support layer to partially expose the capillaries to form a window portion for irradiation and detection and a sample injection portion for injecting a sample.

Electrophoresis member, production thereof and capillary electrophoresis apparatus

Single molecule measurement is conducted by propagating a laser light under multiple reflection between two substrates constituting a flow channel for flowing a sample solution, exciting target molecules in the sample, detecting one-dimensional images of generated fluorescence by a one-dimensional detection portion, synthesizing two-dimensional images from the obtained one-dimensional images by a data synthesizing portion and measuring the concentration of target molecules in the sample solution by counting the number of target molecules based on the two-dimensional images, thereby measuring the concentration of the target molecules in the sample solution. These constitutions for single molecule measurement lead to high precision determination of a micro-amount of a biological material.

Counting system for fluorescent molecules

The disclosed invention provides methods and instruments for fluorescence detection making it possible to separate and detect analytes of a plurality of species in a migration (separation) channel with length of the order of millimeters. Analyte samples disperse across the whole detection region of a migration channel filled with a sieving matrix. Electrodes located in contact with a power supply and the sieving matrix cause the analytes to electophoretically migrate at predetermined velocity V. The detection region is irradiated by excitation light whose intensity changes in a cycle equaling pitch p in the direction that the analytes move. Fluorescence emission from the analytes exposed to the excitation light is detected by a detector. Fluctuation &dgr;i (t) of output current from the detector is analyzed by a spectrum analyzer and the obtained spectrum is displayed. Florescence detection according to the invention is not affected by band broadening of analytes injected into the sample injection end of the migration channel.

Methods and instruments for fluorescence detection

According to an aspect of the present invention, there is provided an inspection apparatus using an optical interferometer including splitting and combining means ( ) for splitting light from a light source ( ) into incident light ( ) irradiated on a sample and reference light ( ) and combining signal light which is light scattered or reflected by the sample ( ) and the reference light, a modulator ( ) for subjecting the reference light to phase modulation and a photo detector ( ) for detecting light combined by the splitting and combining means ( ), the inspection apparatus further including first detecting means ( - ) for detecting amplitudes of first signal components having frequencies of multiples of odd numbers of a fundamental modulation frequency of the modulator in a signal from the photo detector ( ), second detecting means ( - ) for separating and detecting amplitudes of second signal components having frequencies of multiples of even numbers of the fundamental modulation frequency in the signal from the photo detector and means ( ) for calculating an intensity of the signal light by using the amplitudes of the first and the second signal components for providing high signal stability and signal-to-noise ratio and in measuring a sample of a biomedical tissue or the like having large scattering or attenuation of light, distributions of a refractive index and an extinction coefficient up to a portion having a large depth can be measured with high accuracy.

Growing community of inventors

Kokubunji, Japan

Tsuyoshi Sonehara