Hitachi, Ltd.

Hitachi Tokyo Electronics Co., Ltd.

Hitachi-high-technologies Corporation

Takashi Irie

Kazunori Okano

Yasuhiro Mitsui

Hideki Kambara

Chihiro Uematsu

Kenji Yasuda

Takashi Anazawa

Masao Kamahori

Tomoharu Kajiyama

Hiroko Matsunaga

Keiji Hasumi

Kazuaki Mizokami

Takeshi Fujita

Hideki Hasegawa

Hisaya Murakoshi

Satoshi Takahashi

Ken Ninomiya

Kyoko Kojima

Hiroshi Kakibayashi

Tsuyoshi Sonehara

Masaharu Kiyama

Keiichi Kanehori

Michimasa Funabashi

Hidekazu Okuhira

Jiro Tokita

Katsuhiko Itoh

Kazuo Nakano

Takeshi Tajima

Katsumi Kuriyama

Sadao Matsuoka

Takamichi Muramatsu

A fluorescence analyzing method includes the steps of irradiating a board, to which oligonucleotide is fixed, with light for fluorescence measurement; focusing produced fluorescence to form an image; and detecting the fluorescence with a two-dimensional sensor. Here, the board is provided with plural regions to which the oligonucleotide is fixed, and the plural regions are spaced apart from one another on the board substantially equidistantly in the vertical and horizontal directions. A fluorescent image is detected in a condition where the following equation is satisfied:where ds denotes the interval between the regions, M denotes the imaging magnification of an optical focusing/imaging system, dd denotes the pixel pitch of the two-dimensional sensor, and n denotes an integer (n=1, 2, 3, 4, 5).

Fluorescence analyzing method, fluorescence analyzing apparatus and image detecting method

A capillary electrophoresis system includes a plurality of capillaries arranged in parallel on a vertical plane at an identical distance from each other, each of which has a sample injection end immersed in a cathode bufferand pointed downward vertically to facilitate connection between the cathode bufferand a sample solution. The sample elution end is connected via a pump blockand a connection tubeto an anode bufferThe height is made identical between the liquid levels for buffersandto prevent movement of the separation medium in the capillaries. The sample introduced from the sample injection endmoves upward vertically via electrophoresis to the sample elution end in the capillary and is passed through and detected at the fluorescence detection position. The effective separation length is thus decreased to 10 cm or less to attain high throughput.

Capillary electrophoresis system

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

Adenylation of a DNA fragment with a DNA polymerase occurs in the course of PCR, and thus two peaks are detected. To prevent the peak splitting, it is necessary to raise efficiency of adenylation a single peak to occur without changing reaction conditions. To this end, four types of PCR primers which, respectively, have an anchor sequence at 5&prime; terminus so that any of A, C, G or T is attached to at the 5&prime; terminus of the anchor sequence, and PCR is carried out by use of the respective primers to determine efficiencies of adenylation. Subsequently, an anchor sequence that is more likely to undergo adenylation is screened to decide an anchor sequence more likely undergo adenylation, followed by PCR by use of a primer having the decided anchor sequence.

PCR primers and a method for deciding a base sequence thereof regarding adenylation

A capillary electrophoresis system includes a plurality of capillaries arranged in parallel on a vertical plane at an identical distance from each other, each of which has a sample injection end immersed in a cathode buffer and pointed downward vertically to facilitate connection between the cathode buffer and a sample solution. The sample elution end is connected via a pump block and a connection tube to an anode buffer . The height is made identical between the liquid levels for buffers and to prevent movement of the separation medium in the capillaries. The sample introduced from the sample injection end moves upward vertically via electrophoresis to the sample elution end in the capillary and is passed through and detected at the fluorescence detection position . The effective separation length is thus decreased to 10 cm or less to attain high throughput.

There are beforehand prepared a monomer having a reaction residue and a polynucleotide probe set comprising plural kinds of polynucleotide probes having a residue bonded to the reaction residue. The monomer is mixed with each kind of polynucleotide probes comprising any plural probes selected from the polynucleotide probe set. Each kind of the resultant mixtures is added to each of different small holes to make the mixture into gel matrix. Thus, a polynucleotide probe chip is produced. Sample DNA is forcibly migrated in the gels by electrophoresis. Laser light is projected onto the side face of the chip. The fluorescence emitted from the whole surface of the chip is collectively detected with a high-sensitive two-dimensional detector. Thus, the polynucleotide probe chip, holding various kinds of DNA probes, for detecting DNA can be provided. This chip has high hybridization-efficiency and makes high-sensitivity and high-speed DNA detection possible.

Polynucleotide chip probe and polynucleotide detection method

Focusing that abundant class genes abundantly present in a nucleic acid sample can comparatively easily be analyzed and readily be removed in a selective manner, a nucleic acid sample for expression analysis of rare expressed genes can be obtained by removing abundant genes therefrom, and analyses based upon the sample can be achieved.

Preparation method of nucleic acid sample for rare expressed genes and analyzing method using the prepared nucleic acid samples thereby

An apparatus for the separation and fractionation of differentially expressed gene fragments includes a separating means including a capillary filled with a separation medium to separate DNA fragments by electrophoresis, a sampling means including sampling vessels to fractionate and sample the separated DNA fragments, according to their size, a transferring means to transfer buffer solution containing the separated DNA fragments to the sampling means, and a control means to control the sampling means based on a signal gained by detecting means, wherein a voltage for the electrophoresis and a length of the capillary are adjusted such that a spread in time of the separated DNA fragments caused by the transferring means during the transfer of the separated DNA fragments to the sampling vessels is smaller than a difference in separation time of the DNA fragments in the separating means.

Apparatus for the separation and fractionation of differentially expressed gene fragments

Polynucleotide probe chip and polynucleotide detection method

A transmission electron microscope makes it possible to search for defects without applying an undesirable treatment to a specimen by using a reference specimen prepared separately from a specimen to be observed. A pair of specimen holders detachable from the column of the electron microscope are adjacently arranged at upper and lower stages respectively along an electron beam axis to position the specimens closely to each other in an electron beam illuminating position. The pair of holders can be independently set to or removed from the electron beam illuminating position. The specimen holders include devices for selectively finely adjusting the spacing between the specimens, the angle of the specimen with respect to the electron beam axis and with respect to a plane perpendicular to the electron beam axis.

Defect observing electron microscope

A mass spectrometer for analyzing trace impurities on a level between ppt and ppb contained in silicon material gas such as monosilane gas. The mass spectrometer includes an ion formation region, reaction region, and mass analysis region. Ion formation gas is introduced into the ion formation region and sample gas (silicon material gas) is introduced into the reaction region. The ion formation region ionizes ion formation gas by an ionizer and forms primary ions. When the pressure of ion formation gas is made higher than the pressure of sample gas, the ion formation gas flows into the reaction region from the ion formation region together with primary ions and is mixed with the sample gas. In the reaction region, an ion-molecule reaction is produced between the primary ions and trace impurities contained in the sample gas and the trace impurities contained in the sample gas are ionized. The ion intensity of trace impunities, the concentration of trace impurities in the sample gas is determined using a calibration curve. When the gas pressure in the reaction region is kept at almost 1 atmosphere, the reaction is promoted and when the ion-molecule reaction time is optimized according to the size of the reaction region and the voltage condition, impurities on a level between ppt and ppb can be detected and determined.

Atmospheric pressure ionization mass spectrometer

An atmospheric pressure, elevated temperature gas desorption apparatus which enables quanitiative analysis of impurities absorbed in or on the surface of a solid sample (semiconductor wafer, optical disc, etc.) is disclosed. The atmospheric pressure, elevated temperature gas desorption apparatus for desorbing impurities absorbed in or on the surface of a plate-like solid sample 18 into a carrier gas 19 in a chamber 6 under an atmospheric pressure while increasing the temperature of the solid sample 18 includes a desorption room 7A provided in the chamber 6 and connected through to a first gas supply system 1 for supplying the carrier gas 19, for desorbing impurities absorbed in or on the surface of the solid sample 18 into the carrier gas 19. A sample support room 7B is provided in the chamber 6 and is separated from the desorption room 7A by a partition member 6A. The solid sample 18 is in close contact with the partition member 6A. A heater 8 for heating the solid sample 18 is in close contact with the partition member 6A. A reserve room 9 is connected to the sample support room 7B and to a second gas supply system 13 for supplying a purge gas.

Atmospheric pressure, elevated temperature gas desorption apparatus

Ultra-low concentrations of impurities such as water in a highly-purified gas are analyzed by a system having an ion source chamber and a drift chamber. The ion source chamber ionizes one of a sample gas and a carrier gas to produce main component ions, and the other of the sample gas and carrier gas is introduced into the drift chamber. The invention controls the residence time of main component ions in one of the first and second chambers to be shorter than the mean reaction time of main component ions and impurity molecules of the sample gas in the one of the first and second chambers.

Growing community of inventors

Musashimurayama, Japan

Takashi Irie