MALDI mass spectrometer and matrix observation device

Abstract

The invention provides a matrix observation device where a location to be irradiated with a laser beam that provides high efficiency of the ionization can be found from among sample spots arranged on a sample plate. The device is formed of: a stage 31 on which a sample plate 20 on which a sample is to be arranged is to be placed; a light source unit 40 that emits ultraviolet rays for observation with which the sample plate 20 is irradiated; and an image acquisition unit 50 for detecting light from the sample plate 20 so as to create an optical image, and the sample contains a matrix that absorbs the ultraviolet rays for observation.

Claims

1. A matrix assisted laser desorption ionization (MALDI) mass spectrometer for analyzing a sample containing a matrix that absorbs light having a particular wavelength rage, comprising: a stage on which a sample plate on which a sample is to be arranged is to be placed; a first light source unit that emits light for observing a distribution of the matrix in the sample, the first light source unit positioned to direct light to a region on the sample plate on which the sample is arranged; and an image acquisition unit for detecting light from said sample plate to generate the distribution of the matrix in the sample; a second light source unit that emits laser light for being absorbed by the matrix in the sample, the laser light being within said particular wavelength range; and a mass spectrometry unit for carrying out mass spectrometry on a gasified or ionized sample that has been emitted from said sample irradiated with said laser beam, wherein a wavelength range of the light that is emitted from said first light source unit overlaps said particular wavelength of said laser light from the second light source unit.

2. The matrix assisted laser desorption ionization (MALDI) mass spectrometer according to claim 1, wherein said particular wavelength range is an ultraviolet range or an infrared range.

3. The matrix assisted laser desorption ionization (MALDI) mass spectrometer according to claim 2, wherein said first light source unit emits ultraviolet rays or infrared rays in the direction that forms a predetermined angle relative to the vertical direction, and said image acquisition unit is an ultraviolet ray camera or an infrared ray camera for detecting the ultraviolet rays or infrared rays reflected from an upper surface of said sample plate so as to create an optical image.

4. The matrix assisted laser desorption ionization (MALDI) mass spectrometer according to claim 2, wherein said first light source unit emits ultraviolet rays or infrared rays in the direction that forms a predetermined angle relative to the vertical direction, and said image acquisition unit is a visible light camera for detecting the visible light that has been emitted from the plurality of areas for placement of sample arranged on an upper surface of said sample plate so as to create an optical image.

5. The matrix assisted laser desorption ionization (MALDI) mass spectrometer according to claim 1, wherein said matrix has an absorbance band in an ultraviolet or infrared region.

6. The matrix assisted laser desorption ionization (MALDI) mass spectrometer according to claim 1, wherein a number of samples are arranged on an upper surface of said sample plate.

7. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 1, wherein the sample plate is arranged on the stage, and wherein the sample plate comprises the sample having the matrix which is selected from DHB (2,5-dihydroxybenzolate) and CHCA (alpha-cyano-4-hydroxycinnamate).

8. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 1, wherein the first light source unit is a visible light source that provides visible light onto the sample.

9. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 8, where the image acquisition unit is a visible light camera for acquiring a visible light image.

10. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 9, wherein the second light source unit is a laser emission unit emitting ultraviolet rays.

11. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 10, wherein the laser emission unit is a nitrogen laser emitting at a wavelength of 337 nm or a or solid state laser emitting at a wavelength of 355 nm.

12. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 8, wherein the first light source unit is a halogen lamp.

13. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 10, wherein the matrix absorbs UV light from the laser emission unit and emits visible light detectable by the visible light camera.

14. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 1, wherein the first light source unit is an ultraviolet light source that provides ultraviolet light onto the sample, and wherein the ultraviolet light source unit provides a range of wavelengths.

15. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 14, wherein the ultraviolet light source is an LED light source.

16. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 14, wherein a wavelength at the center of the range of wavelengths of the ultraviolet rays emitted from the first light source unit is within +/−20 nm from the wavelength at the center of said particular wavelength range emitted by the second light source unit, and wherein the second light source unit is a laser emitting unit emitting a laser beam.

17. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 14, wherein the image acquisition unit is an ultraviolet ray camera and where areas on the matrix that absorb ultraviolet rays appear dark compared to other areas.

18. A matrix assisted laser desorption ionization (MALDI) mass spectrometer, comprising: a stage on which a sample plate is provided, the sample plate having a plurality of areas on an upper surface of the sample plate for the placement of samples to be analyzed; a first light source unit that emits a light for observation with which said sample plate is irradiated, wherein the first light source is positioned so as to direct the first light onto the plurality of areas for placement of samples on the upper surface of the sample plate, the first light being emitted in said particular wavelength range; and an image acquisition unit for detecting first light from said sample plate so as to create an optical image for identifying a particular portion of the plurality of areas to be irradiated with a second light, a second light source unit that comprises a laser and that emits a second light for being directed at an identified particular portion and where the second light is capable of being absorbed by a matrix at said particular portion, the second light being laser light in said particular wavelength range and overlapping with a wavelength of the first light; and a mass spectrometry unit for carrying out mass spectrometry on a gasified or ionized sample that has been emitted due to irradiation of the matrix in said particular portion with said laser.

19. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 18, wherein the plurality of areas on an upper surface of the sample plate for the placement of samples to be analyzed are a plurality of wells formed in an array on the surface of the sample plate.

20. The matrix assisted laser desorption ionization (MALDI) mass spectrometer of claim 19, wherein the sample plate is a conductive metal sample plate, and wherein the plurality of wells comprise dried samples which have crystals of matrix and sample.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a diagram showing a configuration of the first embodiment;

(2) FIG. 2 is a diagram showing another configuration of the first embodiment;

(3) FIG. 3 is a diagram showing a configuration of the second embodiment;

(4) FIG. 4 is a diagram showing the configuration of an example of a conventional MALDI-TOFMS; and

(5) FIG. 5 is a diagram showing the configuration of another example of a conventional MALDI-TOFMS.

DETAILED DESCRIPTION OF EMBODIMENTS

(6) In the following, embodiments of the present invention are described in reference to the drawings. Here, the present invention is not limited to the embodiments described in the following but includes various modifications as long as the gist of the present invention is not deviated from.

1. First Embodiment

(7) FIGS. 1 and 2 diagrams showing the configurations of the MALDI-TOFMS according to the first embodiment of the present invention. Here, the same symbols are attached to the same components as those in the above-described MALDI-TOFMS 201, and the descriptions thereof are not repeated.

(8) A MALDI-TOFMS 1 is provided with: a mass spectrometry unit 10; a sample plate 20; a sample stage 31 on which the sample plate 20 is to be mounted; a stage drive unit 32 for moving the sample stage 31; an ultraviolet ray source unit (light source unit) 40 for irradiating the upper surface of the sample plate 20 with ultraviolet rays for observation; an image acquisition device (image acquisition unit) 50 for acquiring an image of the upper surface of the sample plate 20; a laser emitting unit 5 for emitting a laser beam for ionization to the sample; and a computer 60 for controlling the entirety of the MALDI-TOFMS 1.

(9) The ultraviolet ray source unit 40 is provided with: an ultraviolet ray LED 41 for emitting ultraviolet rays for observation; and a reflection mirror 42. Thus, the ultraviolet rays emitted from the ultraviolet ray LED 41 are reflected from the reflection mirror 42, and after that, a predetermined range on the upper surface of the sample plate 20 is irradiated with the ultraviolet rays in the direction that forms a set angle α relative to the Z direction (vertical direction).

(10) It is preferable for the wavelength range of the above-described ultraviolet rays for observation emitted from the ultraviolet ray source unit 40 to be a wavelength range that includes the wavelength of 337 nm of the laser beam from the nitrogen laser or the wavelength of 355 nm of the laser beam from the solid-state laser. Alternatively, it is preferable for the wavelength at the center of the above-described ultraviolet rays to be close to the wavelength at the center of the laser beam that is emitted from the laser emitting unit. It is more preferable for the wavelength at the center of the above-described ultraviolet rays to be within +/−20 nm from the wavelength at the center of the laser beam emitted from the laser emitting unit. In addition, it is preferable for the above-described set angle α to be 45° or smaller (predetermined angle or a smaller angle).

(11) The image acquisition device 50 is provided with: an ultraviolet ray camera 51 for acquiring an ultraviolet ray image (optical image); and a reflection mirror 52. Thus, the ultraviolet rays reflected from the upper surface of the sample plate 20 in the direction that forms 45° relative to the upper surface of the sample plate 20 are reflected from the reflection mirror 52, and after that detected by the ultraviolet ray camera 51, and as a result, an ultraviolet ray image, which is an image of a predetermined range on the upper surface of the sample plate 20, is acquired.

(12) The computer 60 is provided with a CPU 61, an input unit 62 and a display unit 63. The functions resulting from the process by the CPU 61 are described by referring to them as units as follows. The CPU 61 has: a stage control unit 61a for controlling the stage drive unit 32 on the basis of an input signal from the input unit 62; a display control unit 61b for controlling the ultraviolet ray source unit 40 and taking in an ultraviolet ray image that has been acquired by the image acquisition device 50 so as to display the ultraviolet ray image on the display unit 63; and an analysis control unit 61c for controlling the nitrogen laser 6 and digitizing a sample signal from the ion detector 11 so as to carry out an appropriate data process.

(13) In the MALDI-TOFMS 1, an operator drips a sample solution gained by mixing DHB or CHCA with a substance to be analyzed into wells on the upper surface of the sample plate 20 and dries the sample solution so as to arrange a sample. Next, the sample plate 20 is placed on the sample stage 31, and after that, the sample stage 31 is moved to find a location that seems to be appropriate for ionization by using the input unit 62 while observing the ultraviolet ray image before the start of the analysis. Thus, the sample is positioned on the upper surface of the sample plate 20 so as to be located within a range irradiated with a laser beam. At this time, ultraviolet rays are absorbed in the location where the matrix is distributed, which is thus observed as a black shadow in the ultraviolet ray image, and therefore, the distribution of the matrix (crystal) can be observed precisely.

2. Second Embodiment

(14) FIG. 3 is a diagram showing the configuration of the MALDI-TOFMS according to the second embodiment of the present invention. Here, the same symbols are attached to the same components as those in the above-described MALDI-TOFMS's 1 and 201, and the descriptions thereof are not repeated.

(15) A MALDI-TOFMS 101 is provided with: a mass spectrometry unit 10; a sample plate 20; a sample stage 31 on which the sample plate 20 is to be mounted; a stage drive unit 32 for moving the sample stage 31; an ultraviolet ray source unit (light source unit) 140 for irradiating the upper surface of the sample plate 20 with ultraviolet rays for observation; an image acquisition device (image acquisition unit) 250 for acquiring an image of the upper surface of the sample plate 20; a laser emitting unit 5 for emitting a laser beam for ionization to the sample; and a computer 160 for controlling the entirety of the MALDI-TOFMS 101.

(16) The ultraviolet ray source unit 140 is provided with an ultraviolet ray LED 141 for emitting ultraviolet rays for observation. Thus, a predetermined range on the upper surface of the sample plate 20 is irradiated with ultraviolet rays emitted from the ultraviolet ray LED 141 in the direction that forms a set angle β relative to the Z direction (vertical direction).

(17) Here, it is preferable for the wavelength range of the ultraviolet rays emitted from the ultraviolet ray source unit 140 to be a wavelength range that includes the wavelength of 337 nm of the laser beam from the nitrogen laser or the wavelength of 355 nm of the laser beam from the solid-state laser. Furthermore, it is preferable for the wavelength at the center of the above-described ultraviolet rays to be close to the wavelength at the center of the light emitted from the laser emitting unit. It is more preferable for the wavelength at the center of the above-described ultraviolet rays to be within +/−20 nm from the wavelength at the center of the light emitted from the laser emitting unit. Furthermore, it is preferable for the above-described set angle β to be 45° or larger (predetermined angle or a larger angle).

(18) The computer 160 is provided with a CPU 161, an input unit 62 and a display unit 63. The functions resulting from the process by the CPU 161 are described by referring to them as units as follows. The CPU 161 has: a stage control unit 61a for controlling the stage drive unit 32 on the basis of an input signal from the input unit 62; a display control unit 161b for controlling the ultraviolet ray source unit 140 and taking in a visible light image that has been acquired by the image acquisition device 250 so as to display the visible light image on the display unit 63; and an analysis control unit 61c for controlling the nitrogen laser 6 and digitizing a sample signal from the ion detector 11 so as to carry out an appropriate data process.

(19) In the MALDI-TOFMS 101, an operator drips a sample solution gained by mixing DHB or CHCA with a substance to be analyzed into wells on the upper surface of the sample plate 20 and dries the sample solution so as to arrange a sample. Next, the sample plate 20 is placed on the sample stage 31, and after that, the sample stage 31 is moved to find a location that seems to be appropriate for ionization by using the input unit 62 while observing the visible light image before the start of the analysis. Thus, the sample is positioned on the upper surface of the sample plate 20 so as to be located within a range irradiated with a laser beam. At this time, ultraviolet rays that are absorbed by the matrix are emitted as visible light, and thus, the place where the matrix is distributed in the visible light image looks brighter, and therefore, the distribution of the matrix (crystal) can be observed precisely.

3. Other Embodiments

(20) (1) Though the MALDI-TOFMS's 1 and 101 are illustrated in the above-described embodiments, the present invention provides a matrix observation device for finding a place to be irradiated with a laser beam that provides high efficiency in ionization, and thus can be applied to analyzers having a MALDI ion source in general. In addition, the present invention can be applied to either vacuum MALDI or atmospheric pressure MALDI.

(21) (2) Though the MALDI-TOFMS's 1 and 101 are illustrated to have a configuration that is provided with a laser emitting unit 5 having a nitrogen laser 6 and an ultraviolet ray source unit 40 or 140, the configuration may be provided with a laser emitting unit having an IR (infrared) laser for emitting infrared rays for ionization and an infrared ray source unit for emitting infrared rays for observation.

(22) At this time, a sample solution that is gained by mixing a matrix of a substance having an absorbance band in an infrared region with a substance to be analyzed is dripped and dried in order to arrange a sample. In the case where urea, DHB, succinic acid, sinapic acid or the like is used as a matrix, for example, the state of ionization differs depending on the location that is irradiated with infrared rays, and therefore, the present invention is particularly effective.

INDUSTRIAL APPLICABILITY

(23) The present invention can be appropriately applied to a MALDI mass spectrometer.

REFERENCE SIGNS LIST

(24) 1 MALDI-TOFMS (MALDI mass spectrometer) 20 sample plate 31 sample stage 40 ultraviolet ray source unit (light source unit) 50 image acquisition device (image acquisition unit)