Preparation method, mass spectrometry method, and mass spectrometer

Abstract

To enable a user to easily prepare a highly uniform crystal in which a sample and a matrix are mixed in the preparation of the sample in mass spectrometry by a MALDI (matrix-assisted laser desorption ionization) method.SOLUTION: A sample preparation method in mass spectrometry by a MALDI method includes a step S12 of preparing a mixed solution of a liquid containing a compound to be subjected to mass spectrometry and a matrix liquid on a sample plate, and a step S10 and a S14 of adjusting the temperature of the sample plate to a temperature within a preparation range. The temperature in the preparation range is 30-60 °C.SELECTED DRAWING: Figure 4

Description

[Technical Field]

[0001] The present invention relates to a preparation method, a mass spectrometry method, and a mass spectrometry apparatus, and more particularly to a technique for improving detection sensitivity in mass spectrometry. [Background technology]

[0002] Mass spectrometry is an analytical technique that converts the chemical substance being measured into ions, separates and detects the ions derived from the chemical substance based on their mass-to-charge ratio (m / z), and reveals the molecular weight, molecular structure, amount present, and form of existence of the chemical substance.

[0003] In mass spectrometry, the sample ionization process is an important step that affects sensitivity and reproducibility, and many methods have been developed to date, such as matrix-assisted laser desorption ionization (MALDI) and electrospray ionization.

[0004] The MALDI method is a method in which a mixed crystal of a sample and a matrix, which is a substance that assists in ionization of the sample, is prepared, and the mixed crystal is irradiated with laser light to ionize the sample together with the matrix.

[0005] The matrix is ​​a crystalline organic small molecule that absorbs laser light. When performing mass spectrometry using the MALDI method, the uniformity of the degree of mixing of the sample and matrix in the mixed crystal affects the detection sensitivity and analytical accuracy of the mass spectrometry. Regarding the formation of matrix crystals, Japanese Patent Laid-Open Publication No. 2013-137294 (Patent Document 1) discloses a technology that enables the formation of a highly uniform matrix film by heating and sublimating the matrix in a vacuum. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-137294 Summary of the Invention [Problem to be solved by the invention]

[0007] However, in Patent Document 1, the chamber in which the sample plate on which the matrix crystals are formed is placed must be evacuated, which places a heavy burden on the user.

[0008] The present disclosure has been made in consideration of these circumstances, and its purpose is to enable users to easily prepare highly uniform crystals in which a sample and a matrix are mixed. [Means for solving the problem]

[0009] A preparation method according to a first aspect of the present disclosure is a method for preparing a sample for mass spectrometry using the MALDI method, and includes the steps of preparing a mixed solution of a solution containing a compound to be subjected to mass spectrometry and a matrix solution on a sample plate, and adjusting the temperature of the sample plate to a temperature within a preparation range, the temperature within the preparation range being 30 to 60°C.

[0010] A mass spectrometry method according to a second aspect of the present disclosure is a mass spectrometry method using a MALDI method, and includes the steps of preparing a mixed solution of a solution containing a compound to be subjected to mass spectrometry and a matrix solution on a sample plate, adjusting the temperature of the sample plate to a temperature within a preparation range, and performing mass spectrometry using the sample plate by a matrix-assisted laser desorption / ionization method to obtain a mass spectrum, wherein the temperature within the preparation range is 30 to 60°C.

[0011] A mass spectrometer according to a third aspect of the present disclosure includes a mass analysis mechanism and a temperature adjustment mechanism that adjusts the temperature of a sample plate used in the mass analysis mechanism to a temperature within an adjustment range, the temperature within the adjustment range being 30 to 60°C. [Effects of the Invention]

[0012] According to the present disclosure, by adjusting the temperature of the sample plate within the preparation range, the user can easily prepare highly uniform crystals in which the sample and matrix are mixed. [Brief explanation of the drawings]

[0013] [Figure 1] 1 is a block diagram showing a configuration of a mass spectrometer according to an embodiment. [Figure 2] FIG. 2 is a plan view of a sample plate. [Figure 3] FIG. 1 is a diagram showing an outline of a method for preparing a sample to be subjected to mass spectrometry by MALDI according to an embodiment. [Figure 4] 1 is a flowchart showing a process of mass spectrometry using the MALDI method. DETAILED DESCRIPTION OF THE INVENTION

[0014] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference numerals, and description thereof will not be repeated.

[0015] [Overall configuration of the analyzer] 1 is a block diagram showing the configuration of a mass spectrometer 100 according to an embodiment. The mass spectrometer 100 includes a mass analysis unit 1, a temperature control mechanism 30, and a controller 40. The mass spectrometer 100 is generally configured to perform mass analysis by irradiating a laser onto a mixed crystal of a sample and a matrix prepared on a sample plate, and ionizing a substance to be analyzed contained in the sample.

[0016] Analysis in the mass spectrometer 100 includes detecting peaks in a mass spectrum and measuring the mass-to-charge ratio (m / z) of specific or non-specific substances contained in a sample. The m / z corresponding to a peak in a mass spectrum is generally referred to as the "position" or "m / z position" of the peak. Analysis in the mass spectrometer 100 also includes determining whether a specific substance is contained in a sample and calculating the concentration of the specific substance in the sample.

[0017] The mass analysis unit 1 includes a control unit 10 and a measurement unit 20. The mass analysis unit 1 ionizes compounds contained in a sample and obtains a mass spectrum.

[0018] The measurement unit 20 includes an ionization unit 21, an ion acceleration unit 22, a mass separation unit 23, and a detection unit 24. The measurement unit 20 ionizes substances in a sample using high voltage, separates the ions S according to their time of flight, which correlates with m / z, and then detects them. In Figure 1, the movement of ions S in the measurement unit 20 is schematically indicated by arrows A1, A2, and A3.

[0019] The ionization unit 21 ionizes substances in the sample by the MALDI method. The ionization unit 21 includes an ion source having a sample plate holder (not shown) that supports the sample plate P and a laser device (not shown) that irradiates laser light onto the sample plate P. The type of laser device is not particularly limited as long as it can emit light that is absorbed by the selected matrix. The laser device is, for example, a nitrogen laser.

[0020] The sample plate P is a typical MALDI plate, such as a plate made of stainless steel or conductive resin. The sample plate P may also be subjected to a surface treatment, such as a water-repellent treatment, to improve sensitivity. The user drops a mixed solution of sample and matrix onto the sample plate P. When the solvent in the mixed solution evaporates, mixed crystals of sample and matrix are formed on the sample plate P. The sample plate P with the mixed crystals formed on its surface is placed in a sample plate holder inside the vacuum chamber of the ionization unit 21. A mixed solution prepared in advance may be dropped onto the sample plate P, or the sample solution and matrix solution may be mixed on the sample plate to form droplets of the mixed solution.

[0021] The ionization unit 21 reduces the pressure of a vacuum chamber in which a sample plate P is placed, and then ionizes the crystals on the sample plate P by irradiating them with laser light. The ions S generated in the ionization unit 21 are extracted by an electric field created by an extraction electrode (not shown) and introduced into the ion acceleration unit 22 as indicated by arrow A1 in FIG.

[0022] The ion acceleration unit 22 includes an acceleration electrode 221 and accelerates the introduced ions S. The flow of the accelerated ions S is appropriately converged by an ion lens (not shown) and introduced into the mass separation unit 23 as indicated by arrow A2 in FIG.

[0023] The mass separation unit 23 includes a flight tube 231, and separates the ions S based on the difference in flight time when each ion S flies inside the flight tube 231. While an example of a linear type flight tube 231 is shown in FIG. 1, a reflectron type or multi-turn type flight tube can also be used. Note that the method of mass analysis is not particularly limited as long as it can separate and detect ions S derived from compounds contained in the sample.

[0024] The detection unit 24 is equipped with an ion detector, detects the ions S separated by the mass separation unit 23 as indicated by arrow A3, and outputs a detection signal with an intensity corresponding to the number of ions incident on the detection unit 24. The detection signal output from the detection unit 24 is input to the processing unit 11 of the control unit 10. In Fig. 1, the flow of the detection signal of the ions S from the detection unit 24 of the measurement unit 20 is schematically indicated by arrow A4.

[0025] The control unit 10 includes a processing unit 11, a memory unit 12, and an input / output unit 13. The control unit 10 comprehensively controls the operation of the measurement unit 20 and processes data obtained by the measurement unit 20. Some or all of the functions of the control unit 10 may be located in a computer or server physically separated from the measurement unit 20.

[0026] Processing unit 11 includes a processor and functions as the main unit for controlling mass spectrometer 100. The processor is, for example, a CPU (Central Processing Unit) and an MPU (Multi-Processing Unit). Processing unit 11 executes programs stored in storage unit 12 to perform various processes.

[0027] The processing unit 11 includes an apparatus control unit 111 , a mass spectrum creation unit 112 , a mass spectrum analysis unit 113 , and a calibration unit 114 .

[0028] The device control unit 111 controls the operation of the measurement unit 20 based on information about the analysis conditions input from the input unit 131. The information about the analysis conditions includes, for example, at least one of the type of compound to be analyzed, the type of sample matrix, laser intensity, and the number of laser irradiations. In Fig. 1, the control of the measurement unit 20 by the device control unit 111 is schematically indicated by arrow A5.

[0029] The mass spectrum creation unit 112 converts the flight time into m / z from measurement data including the amount of ions detected by the detection unit 24 and the flight time of the ions, and creates a mass spectrum showing the amount of detection corresponding to each m / z.

[0030] The mass spectrum analysis unit 113 detects peaks in the mass spectrum and calculates the m / z corresponding to the detected peak. The mass spectrum analysis unit 113 may estimate the substance corresponding to the calculated m / z based on a mass spectrum database stored in the storage unit 12. Furthermore, the mass spectrum analysis unit 113 identifies components in the sample, calculates the concentration of specific substances in the sample, classifies organisms contained in the sample, and analyzes the structure of substances contained in the sample based on the measured values.

[0031] The calibration unit 114 calibrates the mass spectrum based on the measured and theoretical m / z values ​​of the standard substance. The theoretical m / z value is calculated taking into account the molecular weight, the added ions, and the number of charges. Calibration in mass spectrometry involves correcting the measured m / z value of the standard substance so that it approaches the theoretical m / z value of the standard substance, and applying this correction to the entire spectrum.

[0032] The storage unit 12 includes volatile and non-volatile recording media, such as a read-only memory (ROM), a random access memory (RAM), and a large-capacity storage device.

[0033] The ROM can store programs executed by the processing unit 11. The RAM can temporarily store data generated by the execution of the programs in the processing unit 11 and data input via the input / output unit 13, and can function as a primary storage device. The mass storage device is a non-volatile storage device that stores the theoretical m / z values, the mass spectrum database, the mass spectrum created by the mass spectrum creation unit 112, the measurement data output from the measurement unit 20, and the programs used by the processing unit 11 to execute processing. The mass storage device is, for example, a hard disk drive, a solid state drive, or a flash memory.

[0034] The input / output unit 13 is an interface for inputting and outputting information from and to the outside of the mass spectrometric unit 1. The input / output unit 13 includes an input unit 131, an output unit 132, and a communication unit 133.

[0035] The input unit 131 includes an input device. The input device is, for example, a mouse, a keyboard, and a touch panel. The input unit 131 receives information from a user regarding analysis conditions necessary for controlling the operation of the measurement unit 20 and for the processing work of the processing unit 11.

[0036] The output unit 132 includes a display device. The display device is, for example, a liquid crystal monitor. The output unit 132 displays information related to the measurement by the measurement unit 20 and the results of the processing by the processing unit 11 on the display device.

[0037] The communication unit 133 includes a communication device that can communicate via wireless and / or wired connection over the Internet. The communication unit 133 receives data necessary for processing by the processing unit 11 and transmits data processed by the processing unit 11.

[0038] The type of sample in the present disclosure is not particularly limited, but examples that can be used include enzyme-treated protein solutions, biological samples (e.g., blood, saliva, urine, and cell tissue), agricultural and marine products, pharmaceuticals, and food and beverages.

[0039] The sample contains a compound to be analyzed. The compound to be analyzed in the present invention is not particularly limited, and examples thereof include proteins, peptides, glycoproteins, sugar chains, glycopeptides, lipids, glycolipids, nucleic acids, and synthetic polymers.

[0040] When the target substance is a peptide, the peptide may be isolated or may coexist with other substances. Alternatively, the peptide may be a peptide fragment obtained by digestion of a protein. In this case, the peptide fragment may be provided to the present invention in the state present in the digest. The molecular weight of the peptide is not particularly limited and is, for example, 500 to 15,000. Regarding the physical properties of peptides, peptides include hydrophilic peptides and hydrophobic peptides. Furthermore, peptides include acidic peptides, neutral peptides, and basic peptides. Furthermore, peptides include glycopeptides and lipid peptides.

[0041] The matrix is ​​not particularly limited as long as it is a matrix commonly used in the MALDI method. Examples of the matrix include α-cyano-4-hydroxycinnamic acid (CHCA), 2,5-dihydroxybenzoic acid (DHB), sinapic acid, 2-(4-hydroxyphenylazo)benzoic acid, 2,4,6-trihydroxyacetophenone, 2,6-dihydroxyacetophenone, and 2-mercaptobenzothiazole. From the viewpoint of ionization efficiency, CHCA, DHB, and sinapic acid are generally used as matrices when the target substance is a peptide.

[0042] The temperature adjustment mechanism 30 adjusts the temperature of the sample plate P held by the sample plate holder in the ionization unit 21 to within a temperature adjustment range. The temperature adjustment mechanism 30 is, for example, an incubator, a dryer, an oven, a heating block, a hot plate, or a heating furnace. In the ionization unit 21 of FIG. 1 , the temperature adjustment mechanism 30 may be provided in the ionization unit 21 as a temperature adjustment mechanism, as indicated by the dashed line.

[0043] The preparation range is an example of a temperature range that can rapidly volatilize the solvent contained in the droplets, specifically, 30 to 60°C. If the temperature of the sample plate P is adjusted to the range of 30 to 60°C and mixed crystals are prepared on the sample plate, uniform mixed crystals can be obtained, and the accuracy of mass spectrometry can be improved. As shown in the examples below, a preparation range of 30 to 60°C is sufficient to produce results, but a range of 45 to 50°C is more preferable.

[0044] The controller 40 controls the operation of the temperature adjustment mechanism 30. Specifically, it controls the temperature of the temperature adjustment mechanism 30 so that it falls within the adjustment range. Furthermore, if the sample plate holder is configured to be movable from the temperature adjustment mechanism 30 to the ionization unit 21, it controls the movement of the sample plate holder in addition to the temperature and the time for adjusting the temperature. With this mechanism, the user can prepare droplets on the sample plate P and then place the sample plate P on the sample plate holder. The temperature of the sample plate P is then automatically adjusted to fall within the adjustment range and placed in the ionization unit 21.

[0045] [Conventional method for preparing samples for mass spectrometry using MALDI] When performing mass spectrometry using the MALDI method, the uniformity of the mixture ratio of the sample and matrix in the mixed crystal affects the detection sensitivity and analytical accuracy of the mass spectrometry.

[0046] As a method for making the matrix crystals uniform, there is a vapor deposition method as disclosed in Patent Document 1.

[0047] However, in order to perform the vapor deposition method, it is necessary to create a vacuum inside the chamber in which the sample plate on which the matrix crystals are formed is placed, which requires complicated work for the user.

[0048] Another method involves dropping a mixture of sample and matrix onto a sample plate and allowing the droplets to air-dry to obtain mixed crystals. However, this method involves slow evaporation of the solvent, which can lead to segregation during the crystal formation process. This means that the concentrations of sample and matrix in the solution can vary locally around the crystallization site, making it difficult to obtain uniform mixed crystals. Segregation during the mixed crystal formation process can result in crystals with varying sample and matrix ratios, potentially compromising reproducibility and mass accuracy between laser irradiations in mass spectrometry.

[0049] [Method for preparing a sample to be subjected to mass spectrometry by MALDI method according to the present disclosure] Therefore, in the sample preparation method according to the present disclosure, a mixed solution of sample and matrix is ​​dropped onto a sample plate whose temperature has been adjusted within the preparation range, and after the dropping of the mixed solution, the temperature of the sample plate is further adjusted to a temperature within the preparation range. Since the temperature of the sample plate is adjusted to a temperature within the preparation range, the solvent contained in the droplets can be rapidly evaporated. This suppresses segregation during the mixed crystal production process, allowing for the production of uniform mixed crystals. By using the sample preparation method according to the present disclosure, users can improve the detection sensitivity and analytical accuracy in mass spectrometry more easily than with conventional methods.

[0050] The sample preparation method according to the present disclosure will now be described in detail. Figure 2 is a plan view of an example of a sample plate P used in sample preparation. The sample plate P includes one or more wells W into which a mixed solution is dropped. In the example of Figure 2, 8 x 8 = 64 wells W are formed on the sample plate P. In this way, by including multiple wells W on the sample plate P, multiple samples can be measured at once. The wells W serve as markers when dropping the mixed solution onto the surface of the sample plate P. The wells W are composed of recesses formed on the sample plate P. The thickness of the sample plate P in the Z-axis direction is not particularly limited, but is preferably several millimeters.

[0051] 3 is a diagram showing an outline of a sample plate preparation method according to an embodiment, in which a mixed solution M is placed on a well W of a sample plate P by a pipette 5.

[0052] The temperature of the sample plate P is adjusted to a temperature within the preparation range before the mixed solution is dropped. The time for heating the sample plate P is not particularly limited, but it is preferable that the temperature of the entire sample plate P be uniformly adjusted to the set temperature.

[0053] After the temperature of the sample plate P is adjusted to a temperature within the preparation range, a mixed solution M of a solution containing a compound to be subjected to mass spectrometry and a matrix solution is dropped onto the sample plate P. According to one embodiment, the sample is a trypsin enzyme-treated solution of a protein. The user adds the matrix solution and the trypsin enzyme-treated solution of the protein to a microtube and mixes them well to prepare the mixed solution M. The prepared mixed solution M is dropped onto the sample plate P using a pipette 5. Alternatively, droplets of the mixed solution M may be generated on the sample plate P by mixing the sample solution and the matrix solution.

[0054] After droplets of the mixed solution M are formed in the wells W on the sample plate P, the temperature of the sample plate P is adjusted to fall within the preparation range. The heating time is not particularly limited, but it is preferable to maintain the temperature of the sample plate within the preparation range at least until the solvent contained in the droplets of the mixed solution M volatilizes and mixed crystals of the sample and matrix precipitate as residue.

[0055] Once the solvent has evaporated and a mixed crystal of the sample and matrix is ​​obtained, mass analysis is performed on the mixed crystal using the mass spectrometer 100 .

[0056] The mixed solution may be added dropwise while the temperature of the sample plate P is maintained within the preparation range. This allows droplets of the mixed solution M to be produced while the temperature of the sample plate is maintained within the preparation range, thereby enabling stable and uniform mixed crystals to be obtained.

[0057] [MALDI mass spectrometry processing] 4 is a flowchart showing the process of mass spectrometry using the MALDI method in this embodiment. Of the steps shown in FIG. 4, steps S10 to S14 are performed manually by a user using experimental equipment used in general scientific experiments and mass spectrometry. Of the steps shown in FIG. 4, step S16 is performed by mass spectrometer 100.

[0058] In S10, the user adjusts the temperature of the sample plate P to be within the preparation range.

[0059] In S12, the user generates droplets of a mixed solution M of a solution containing a compound to be subjected to mass spectrometry and a matrix solution in wells W on a sample plate P. When generating the droplets, the temperature of the sample plate P may be adjusted to a temperature within a preparation range.

[0060] In S14, the user adjusts the temperature of the sample plate P to be within the adjustment range. On the sample plate P, the solvent in the droplets of the mixed solution M of the matrix solution and the solution containing the compound to be analyzed by mass spectrometry evaporates, and mixed crystals are precipitated.

[0061] In S16, after the user inserts the sample plate P into the mass spectrometer 100, the mass spectrometer 100 irradiates the mixed crystal prepared in step S14 with a laser to ionize the compounds to be analyzed. Information about the ions detected by the detection unit 24 is processed by the control unit 10 and displayed to the user via the output unit 132. Thereafter, the processing shown in FIG. 4 ends.

[0062] The method for preparing a sample plate according to the present embodiment described above allows users to easily obtain crystals in which the sample and matrix are uniformly mixed. By subjecting the crystals to mass spectrometry, the accuracy of the analysis of compounds contained in the sample can be improved.

[0063] As the preparation method described in the present disclosure, for example, the preparation methods described in JP-A-2003-98154 and JP-A-2014-2087 can also be used.

[0064] [Aspect] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0065] (Item 1) In one aspect, a method for preparing a sample for mass spectrometry using matrix-assisted laser desorption / ionization comprises the steps of preparing a mixed solution of a solution containing a compound to be subjected to mass spectrometry and a matrix solution on a sample plate, and adjusting the temperature of the sample plate to a temperature within a preparation range, which may be 30 to 60°C.

[0066] The preparation method described in item 1 provides a technique that enables users to easily prepare highly uniform crystals in which the sample and matrix are mixed.

[0067] (Item 2) In the preparation method described in item 1, the temperature within the preparation range may be 45 to 50°C.

[0068] The preparation method described in Section 2 provides a technique that enables users to easily prepare more uniform crystals in which the sample and matrix are mixed.

[0069] (Item 3) In the preparation method described in item 1 or 2, the adjusting step may include a step of adjusting the temperature of the sample plate to a temperature within the preparation range after the step of preparing the mixed solution.

[0070] The preparation method described in paragraph 3 provides a technology that suppresses segregation during the process of producing mixed crystals containing the compound to be analyzed by mass spectrometry and a matrix, allowing users to prepare highly uniform crystals containing a mixture of the sample and matrix.

[0071] (Item 4) In the preparation method described in any one of Items 1 to 3, the adjusting step may include a step of adjusting the temperature of the sample plate to a temperature within the preparation range before the step of preparing the mixed solution.

[0072] The preparation method described in Section 4 provides a technology that prevents the rate of solvent evaporation from varying depending on the position on the plate during the process of generating mixed crystals containing the compound to be analyzed by mass spectrometry and a matrix, thereby enabling users to prepare highly uniform crystals in which the sample and matrix are mixed.

[0073] (Item 5) In the preparation method according to any one of items 1 to 4, the adjusting step may be carried out in parallel with the step of preparing the mixed solution.

[0074] The preparation method described in Section 5 provides a technology that enables users to prepare highly uniform crystals in which the sample and matrix are mixed by increasing the rate at which the solvent contained in the mixed solution evaporates.

[0075] (Item 6) In the preparation method according to any one of items 1 to 5, the compound may be a compound containing a glycopeptide.

[0076] The preparation method described in item 6 provides a technique that enables users to easily prepare highly uniform crystals that are a mixture of a sample containing glycopeptides and a matrix.

[0077] (Item 7) In the preparation method according to any one of items 1 to 6, the matrix solution may be a solution containing α-cyano-4-hydroxycinnamic acid or 2,5-dihydroxybenzoic acid.

[0078] The preparation method described in Section 7 provides a technique that allows users to easily prepare highly uniform crystals that are a mixture of a sample and a matrix containing α-cyano-4-hydroxycinnamic acid or 2,5-dihydroxybenzoic acid.

[0079] (Item 8) In one aspect, a method for mass spectrometry using matrix-assisted laser desorption / ionization includes the steps of: preparing a mixed solution of a solution containing a compound to be subjected to mass spectrometry and a matrix solution on a sample plate; adjusting the temperature of the sample plate to a temperature within a preparation range; and performing mass spectrometry using the sample plate by matrix-assisted laser desorption / ionization to obtain a mass spectrum, wherein the temperature within the preparation range may be 30 to 60°C.

[0080] The mass spectrometry method described in item 8 provides a technique for improving detection sensitivity in mass spectrometry.

[0081] (Item 9) In one aspect, the mass spectrometer comprises a mass spectrometry mechanism and a temperature control mechanism that controls the temperature of a sample plate used in the mass spectrometry mechanism to a temperature within a control range, and the temperature within the control range may be 30 to 60°C.

[0082] The mass spectrometer described in item 9 provides a technique for improving detection sensitivity in mass spectrometry.

[0083] (Item 10) The mass spectrometer according to item 9 may further include a controller for controlling the temperature of the temperature adjustment mechanism.

[0084] According to the mass spectrometer described in item 10, the temperature of the sample plate is automatically adjusted.

[0085] (Item 11) In the mass spectrometer according to item 9 or 10, the temperature within the preparation range may be 45 to 50°C.

[0086] The mass spectrometer described in item 10 provides a technique for further improving detection sensitivity in mass spectrometry.

[0087] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims, not by the above description, and is intended to include all modifications within the meaning and scope of the claims. [Explanation of symbols]

[0088] 1 mass analysis unit, 5 pipette, 10 control unit, 11 processing unit, 12 memory unit, 13 input / output unit, 20 measurement unit, 21 ionization unit, 22 ion acceleration unit, 23 mass separation unit, 24 detection unit, 30 temperature control mechanism, 40 controller, 100 mass analyzer, 111 device control unit, 112 mass spectrum creation unit, 113 mass spectrum analysis unit, 114 calibration unit, 131 input unit, 132 output unit, 133 communication unit, 221 acceleration electrode, 231 flight tube.

Claims

1. A method for preparing a sample for mass spectrometry by matrix-assisted laser desorption / ionization, comprising: preparing a mixed solution of a solution containing a compound to be subjected to mass spectrometry and a matrix solution on a sample plate; adjusting the temperature of the sample plate to a temperature within a preparation range; The preparation method, wherein the temperature within the preparation range is 30 to 60°C.

2. 2. The method according to claim 1, wherein the temperature within the preparation range is 45 to 50°C.

3. 3. The preparation method according to claim 1, wherein the adjusting step includes adjusting the temperature of the sample plate to a temperature within the preparation range after the step of preparing the mixed solution.

4. 3. The preparation method according to claim 1, wherein the adjusting step includes adjusting the temperature of the sample plate to a temperature within the preparation range before the step of preparing the mixed solution.

5. The method according to claim 1 or 2, wherein the adjusting step is carried out in parallel with the step of preparing the mixed solution.

6. The preparation method according to claim 1 or claim 2, wherein the compound is a compound containing a glycopeptide.

7. The preparation method according to claim 1 or 2, wherein the matrix solution is a solution containing α-cyano-4-hydroxycinnamic acid or 2,5-dihydroxybenzoic acid.

8. A mass spectrometry method using matrix-assisted laser desorption / ionization, comprising: preparing a mixed solution of a solution containing a compound to be subjected to mass spectrometry and a matrix solution on a sample plate; adjusting the temperature of the sample plate to a temperature within a preparation range; and performing mass spectrometry by the matrix-assisted laser desorption / ionization method using the sample plate to obtain a mass spectrum; The mass spectrometry method, wherein the temperature in the preparation range is 30 to 60°C.

9. a mass spectrometry mechanism; a temperature adjustment mechanism that adjusts the temperature of a sample plate used in the mass spectrometry mechanism to a temperature within a temperature adjustment range; The temperature within the preparation range is 30 to 60°C.

10. The mass spectrometer of claim 9 , further comprising a controller for controlling the temperature of the temperature adjustment mechanism.

11. The mass spectrometer according to claim 9 or 10, wherein the temperature within the adjustment range is 45 to 50°C.

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