Shimadzu Corporation

Osaka University

Keio University

Kinki University

Inter-university Research Institute Corporation National Institutes of Natural Sciences

Hamamatsu University School of Medicine

Kiyoshi Ogawa

Mitsutoshi Setou

Osamu Furuhashi

Takahiro Harada

Kengo Takeshita

Shigeki Kajihara

Hideaki Izumi

Yoshikazu Yoshida

Shuichi Shimma

Sadao Takeuchi

Shinichi Yamaguchi

Masaru Nishiguchi

Yoshihiro Ueno

Michisato Toyoda

Takeharu Etoh

Kazuteru Takahashi

Hiroyuki Miura

Tomomi Tamura

Tohru Kinugawa

Masaaki Matsuura

Kozo Shimazu

Masaru Ushijima

Masatoshi Wakui

A mass spectrometer, includes: a sampling probe that irradiates a specimen disposed in the atmosphere with an electron and obtains a sample separated from the specimen; and a measurement unit that performs mass spectrometry of the sample obtained by the sampling probe, wherein the sampling probe comprises: a casing having an opening which is opened to the atmosphere and an outlet through which the sample is discharged to the measurement unit; and a surface emission type electron emission element housed in the casing such that an electron emission surface thereof opposes to the opening.

Mass spectrometer, sampling probe, and analysis method

A microchannel plate (MCP)in an ion detection sectionmultiplies electrons. An anodedetects those electrons and produces a current signal. An amplifierconverts this signal into a voltage signal. A low-pass filterA acting as a smoothing sectionis located at the output end of the amplifier. A waveform-shaping time adjusteradjusts the time constant of the low-pass filterA beforehand according to the response time of the MCP, mass-to-charge ratio of an ion species to be subjected to the measurement, and duration of the spread of the ion species which depends on device-specific parameters. A plurality of peaks which sequentially appear in the detection signal corresponding to one ion species are thereby smoothed into a single broad peak. Thus, the distinguishability between signal waves and noise components is improved.

Ion analyzer

Provided is a technique for using an optical microscope image of an area on a sample to collect area-specific information characterizing each kind of biological tissue from imaging mass analysis data. On an optical image of a two-dimensional target area on a sample, a difference is examined in the kind of tissue or other features and areas are specified, each regarded as the same kind of tissue. When data processing is initiated, peak information is extracted, for each specified area, from mass spectrum data of all the measurement points. A peak method is applied to each area to extract peak information. Then, when a command to compare a set of areas is given, the peak information of those areas is collected. By comparing the peak information of different areas by a machine learning algorithm or similar judging technique, area-specific peak information is obtained, and this information is stored in memory.

Mass-analysis data processing method and system

To provide a sample preparation device that is appropriate for the formation of a matrix film for MALDI through vacuum vapor deposition. A sample preparation device is provided with: a sample substrate support unitfor supporting a substance to be analyzed on a substrate S so that the substance faces a vapor deposition sourcefor a matrix substance J; a light amount measurement unit for irradiating a matrix film vapor deposited on the substrate S with measurement light diagonally and detecting the amount of measurement light that has transmitted through or has been reflected from the above-described matrix film diagonally; and an adhesion prevention meansfor preventing the matrix substance that has flown off from the above-described vapor deposition sourcefrom adhering to the above-described light amount measurement unit.

Sample preparation device to form a matrix film for matrix assisted laser desorption/ionization method

A sample stage () on which a sample () is placed can be reciprocally moved along a guide () by a driving mechanism (). A cutter () which is moved in an X-Y plane by a driving mechanism () is placed at a sample cutting position (B). When the sample stage () is moved to the sample cutting position (B) and the cutter is driven with the height of the sample stage () being appropriately adjusted, an upper portion of the sampleis horizontally cut off with a predetermined thickness and a new sample analysis surface which was inside the sampleis exposed. Hence, by repeating a mass analysis for a predetermined measurement area at an analysis position (C) and a partial cutting of the sampleat the sample cutting position (B), it is possible to achieve a three-dimensional mass analysis imaging of the sample () without removing the sample () from the sample stage ().

Mass spectrometer

A method creates an accurate mass spectrum with a high resolving power based on a plurality of TOF spectra, while reducing the computation to assure real-time processing. TOF spectra are measured when ions are ejected from the loop orbit. Then a coincidence detection method determines what mass-to-charge ratio a peak appearing on the TOF spectra originates from. The time range in which a corresponding peak appears on other TOF spectra is set, and the existence of the peak in that range is determined. When the corresponding peak is found on other TOF spectra, the m/z is deduced from the peak on the TOF spectrum with the highest resolving power and a mass spectrum is created. From the peak density around the peak of interest, the reliability of the deduction is computed. For a low reliability peak, the ion ejection time is optimized and the TOF spectrum is measured again.

Mass analysis data processing method and mass spectrometer

A mass spectrometer capable of obtaining a clear microscopic observation image with high spatial resolution in real time, even during a mass analysis, without affecting the analysis is provided. An apertureis formed in a stageon which a sample plateto be placed. The sample plateis transparent or translucent. A microscopic observation unit, including an observation optical systemand a CCD camera, is provided below the stageto observe the reverse side of the samplethrough the apertureof the stageas well as the transparent sample plate. The observed image is displayed on the screen of a display unit. If the sampleis a slice of biological tissue, the sample image taken from the reverse side will be substantially the same as an image taken from the obverse side.

The main voltage generator () applies a rectangular-wave radio-frequency voltage to the ring electrode () in order to capture ions inside the ion trap (). In the case where the TOFMS () is operated in the reflectron mode, the radio-frequency voltage is changed into a constant voltage value when the phase thereof is 1.5&#x3c0;, and a voltage for expelling ions is applied to the end cap electrodes () to expel the ions from the exit aperture () and introduce them into the TOFMS (). In this case, since the velocity spread of the ions inside the ion trap () is small and so is the spatial spread thereof, a high mass resolution and accuracy can be achieved while assuring a high detection sensitivity. In the case where the TOFMS () is operated in the linear mode, the radio-frequency voltage is changed into a constant voltage value when the phase thereof is 0.5&#x3c0;, and then the ions are expelled. In this case, a high mass resolution and mass accuracy can be achieved since the variation of the ions' acceleration, which cannot be converged in the linear mode, can be suppressed.

Ion trap time-of-flight mass spectrometer

A sample platewith a sampleplaced thereon is initially set on a stage, and a visual image of the sample is taken with a CCD camera. This image is stored in an image data memory. Then, an operator removes the sample plate, sprays a matrix for a MALDI process onto the sampleand replaces the plate onto the stage. After that, when a predetermined operation is made, a clear image of the sample taken before the application of the matrix is shown on a display unit. On this image, the operator specifies a point or area for the analysis. The samplemay have been displaced due to the removal and replacement of the plate. Accordingly, an image analyzercalculates the direction and magnitude of the displacement, for example, by recognizing the position of the markings provided on the sample plate. A displacement correctorcomputes coordinate values in which the displacement is corrected. Thus, even if a displacement occurs, the mass analysis can be accurately performed on the point or area of the actual sample as specified on the clear visual image taken before the application of the matrix.

A mass spectrometer is provided in which ions are favorably introduced into a loop orbit or favorably led out from the loop orbit without affecting the motion of the ions flying along the loop orbit. An ion-introduction orbitis set to correspond to the orbit (ejection orbit portion) of ions after being bent by the sector-shaped electric field Ein the loop orbit. When ions are introduced, a voltage applied to the electrode unitis put to zero to release the sector-shaped electric field E. Then the ions emitted along the ion-introduction orbitfly straight in the electrode unit. The direction and position of the ions coming out from the exit end of the electric field is the same as those ions flying along the loop orbit. Therefore, there is no need for placing a deflection electrode for introducing/leading-out ions on the loop orbit.

A sample S is irradiated with a two-dimensionally spread ray of laser light to simultaneously ionize substances within a two-dimensional area on the sample. The resultant ions are mass-separated by a TOF mass separatorwithout changing the interrelationship of the emission points of the ions. The separated ions are then directed to a two-dimensional detector sectionthrough a deflection electric field created by deflection electrodesand. The two-dimensional detector sectionconsists of a plurality of detection unitsarranged in parallel, each unit including an MCP, fluorescent plateand two-dimensional array detector. The magnitude of deflecting the flight path of the ions by the deflection electric field is changed in a stepwise manner with the lapse of time from the generation of the ions so that a plurality of mass analysis images are sequentially projected on each detection unit. When the mass analysis image shifts from one detection unit to another, the data acquisition operation by the two-dimensional array detector in the previous detection unit is discontinued. As a result, a predetermined number of the latest images are held inside the detector. Thus, the measurement time can be extended to widen the measurable mass-to-charge ratio range, while ensuring a high mass resolution.

In a mass spectrometer for carrying out mass analysis while microscopically observing a two-dimensional area of a sample, the observation position for selecting a target portion while observing an image of the samplecaptured with a CCD camerais separated from the analysis position for carrying out the mass analysis of the sampleby delivering laser light from the laser-delivering unitonto the sample. The sampleis placed on a stage, which can be precisely moved between the observation position and the analysis position by a stage-driving mechanism. An observation optical systemcan be set close to the sampleat the observation position, without impeding the flight of the ions generated from the sampleduring the analysis or interfering with a laser-condensing optical system. Thus, the spatial resolution for observation is improved without deteriorating the ion-detecting efficiency.

The number of times of repetition of mass spectrometry analysis for integrating mass profiles is reduced to facilitate reduction in measurement time-period and increase a signal intensity. In a state when ions are trapped by a high-frequency electric field formed within an ion trap, a rectangular-wave high-frequency voltage to be applied from a main voltage generation section to a ring electrode is temporarily stopped, and next ions are introduced from an ion entrance port into the ion trap in a state when only a static electric field exists within the ion trap. The high-frequency voltage application is re-started while at least a part of previously-trapped ions remain within the ion trap, to trap the newly-introduced ions in addition to the previous ions so as to increase an amount of ions to be accumulated, and the accumulated ions are subjected to the mass spectrometry analysis.

Ion trap mass spectrometer

Disclosed is an ion trap mass spectrometer for MSanalysis, which comprises a frequency-driven ion trap section operable to trap sample ions and isolate a precursor ion from the sample ions, while setting an ion-trapping RF voltage waveform at a first frequency providing a first low-mass cutoff (LMCO) value, and, then after setting the ion-trapping RF voltage waveform at a second frequency greater than the first frequency to provide a second LMCO value less than the first LMCO value, without changing an amplitude of the ion-trapping RF voltage waveform, to irradiate the precursor ion in a trapped state with light so as to photodissociate the precursor ion into fragment ions; and an analyzer section operable to subject the fragment ions ejected from the ion trap section, to mass spectrometry so as to obtain information about a molecular structure of the precursor ion. The ion trap mass spectrometer of the present invention can maximize a mass range coverable in one cycle of MSanalysis.

Ion trap mass spectrometry

The present invention provides a mass spectrometer capable of breaking even a sample molecule having a large molecular weight by a CID process. In an embodiment of the present invention, the mass spectrometer includes an ionizing sourcefor turning a sample into ions, mass-separating sectionsandfor mass-separating the sample ions, a detecting sectionfor detecting the mass-separated ions, and a collision section (collision cell)located on an ion path extending from the ionizing sourcethrough the mass-separating sectionsandto the detecting section. It also includes a cluster generatorfor producing clusters of atoms or molecules. The clusters produced by the cluster generatorare introduced into the collision cell. The use of the clusters having a huge mass as the target gas in the CID process enables the collision energy of the sample ions to be efficiently assigned to the breaking of the ions.

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Kyoto, Japan

Kiyoshi Ogawa