Mass spectrometer

Abstract

A mass spectrometer (1) in which first ion sources (12)-(17) for spraying and ionizing a liquid sample under atmospheric pressure and a second ion source (111) for irradiating the sample with laser light and ionizing are selectively mounted as ionization units, the mass spectrometer (1) being provided with: mass analysis units (231), (242)-(246) that are provided in a vacuum chamber connected to the ionization units via a partition wall and that perform mass analysis on the sample; separating and detecting ions according to the mass-to-charge ratio; second ion introduction tubes (31, 36) that are provided so as to pass through the partition wall, introduce ions into the vacuum chamber, are longer than the first ion introduction tube used when the first ion source is used, and are used when the second ion source is used; and heating units (37, 38) that heat a portion of the second iontophoresis tube that extends from the first iontophoresis tube to the ionization unit side.

Description

Technical Field

[0001] The present invention relates to a mass spectrometer using an ion source for generating ions by irradiating a sample with laser light in an atmospheric pressure atmosphere. Background Art

[0002] In order to identify or quantify the target substance contained in the liquid sample, a mass spectrometer having an ionization unit that generates ions of the target substance by electrospray ionization (ESI) is used. In ESI, the liquid sample is charged and sprayed into an ionization chamber at approximately atmospheric pressure, and the ions are introduced into the mass spectrometer in the vacuum chamber via an ion introduction tube. The ion introduction tube is arranged so as to penetrate the partition wall between the ionization chamber and the vacuum chamber, and by heating the ion introduction tube, the desolvation of the ions is promoted, thereby improving the efficiency of ion generation.

[0003] In addition, in order to measure target substances contained in biological samples, etc., mass analysis using a mass spectrometer equipped with MALDI is performed (for example, Patent Document 1). MALDI is an ion source that ionizes a sample by a matrix-assisted laser desorption / ionization method.

[0004] There are two types of MALDI: atmospheric pressure MALDI that ionizes a sample under atmospheric pressure and vacuum MALDI that ionizes a sample under vacuum. A mass spectrometer using atmospheric pressure MALDI includes an atmospheric pressure ionization unit (atmospheric pressure MALDI) and a mass spectrometer installed in a vacuum chamber that separates and detects ions based on their mass-to-charge ratio.

[0005] In a mass spectrometer equipped with atmospheric pressure MALDI, mass analysis was performed as follows.

[0006] First, a pretreatment is performed by coating the surface of the sample placed on the sample plate with a substance that is easily ionized, i.e., a matrix substance, so that microcrystals of the matrix substance that have taken in molecules of the sample are formed on the surface of the sample. If the sample plate carrying the pretreated sample is placed at a predetermined position of MALDI and the sample surface is irradiated with laser light, the microcrystals of the matrix substance present on the surface are heated, and the sample molecules taken in the microcrystals are separated and ionized.

[0007] Ions generated from sample molecules are taken in from the inlet end (ion intake) of the ion introduction tube, pass through the ion introduction tube and enter the mass analysis unit. The ions entering the mass analysis unit are separated according to the mass-to-charge ratio and detected by the ion detector. By correlating the signal intensity output from the ion detector with the mass-to-charge ratio of the ion, a mass spectrum is obtained with the mass-to-charge ratio on the horizontal axis and the signal intensity on the vertical axis.

[0008] Although the ionization methods are different in ESI and atmospheric pressure MALDI, the mass spectrometer can use a common mass spectrometer. However, in atmospheric pressure MALDI, the reflector for reflecting the irradiated light to the sample surface and the lens for focusing light are arranged in front of the sample. Therefore, compared with ESI, in atmospheric pressure MALDI, the sample is usually located farther from the vacuum chamber.

[0009] Prior art literature

[0010] Patent Literature

[0011] Patent Document 1: Japanese Patent Application Publication No. 2021-196303

[0012] Non-patent literature

[0013] Non-patent document 1: "Imaging One-Stop Application - From physical property evaluation of administered drugs to metabolomics based on distribution and quantification of drugs or metabolites -", ​​[Online], Shimadzu Corporation, [retrieved on September 7, 2023], URL: https: / / www.an.shimadzu.co.jp / bio / imaging / index.htm> Summary of the invention

[0014] Technical problem to be solved by the invention

[0015] If the ion introduction tube used in ESI is used directly, the distance from the sample to the entrance of the ion introduction tube becomes longer, and the efficiency of ion introduction into the ion introduction tube becomes poor. Therefore, in the case of generating ions by atmospheric pressure MALDI, for example, an extension tube is connected to an ion introduction tube for introducing ions generated by ESI into a vacuum chamber, and the entrance end of the ion introduction tube is arranged near the measurement point. However, it is known that if the extension tube is connected to the ion introduction tube used in ESI and extended, and the ions generated by atmospheric pressure MALDI are introduced into the vacuum chamber, it is sometimes impossible to measure the ions with sufficient sensitivity.

[0016] The technical problem to be solved by the present invention is to improve the measurement sensitivity of ions in a mass spectrometer using an ion source that generates ions by irradiating a sample with laser light under an atmospheric pressure atmosphere.

[0017] Solutions for solving the above technical problems

[0018] The present invention completed in order to solve the above technical problems is a mass spectrometer, which is selectively equipped with a first ion source and a second ion source as an ionization unit, wherein the first ion source sprays a liquid sample under an atmospheric pressure atmosphere to ionize, and the second ion source irradiates a sample with a laser under an atmospheric pressure atmosphere to ionize, and the mass spectrometer comprises:

[0019] A mass analysis unit is provided in a vacuum chamber connected to the ionization unit via a partition wall, and separates and detects ions generated by the ionization unit according to a mass-to-charge ratio;

[0020] a second ion introduction tube, which is provided through the partition wall and introduces ions generated by the ionization section into the vacuum chamber, the second ion introduction tube being longer than the first ion introduction tube used when the first ion source is used and being used when the second ion source is used;

[0021] The heating unit heats a portion of the second ion introduction tube extending from the first ion introduction tube to the ionization unit side.

[0022] Effects of the Invention

[0023] The first ion source for ionizing the liquid sample by spraying is, for example, ESI, atmospheric pressure chemical ionization (APCI), or a dual ion source (DUIS) having both. In addition, the second ion source for ionizing the sample by irradiating the sample with laser in an atmospheric pressure atmosphere is, for example, atmospheric pressure MALDI or surface assisted laser desorption ionization (SALDI).

[0024] If the ion introduction tube used in ESI and APCI is directly used when using atmospheric pressure MALDI, etc., the distance from the entrance end of the ion introduction tube to the measurement point becomes longer, and the efficiency of ion introduction into the ion introduction tube becomes worse. Therefore, in the present invention, when using the second ion source, a second ion introduction tube that is longer than the first ion introduction tube used when using the first ion source is used. According to the discovery obtained by the inventors, the reason why ions could not be measured with sufficient sensitivity when using the second ion introduction tube in the past was that the part of the second ion introduction tube extending from the first ion introduction tube to the ionization part side was not heated and became low temperature. In the mass spectrometer involved in the present invention, by using a heating part to heat the part of the second ion introduction tube extending from the first ion introduction tube to the ionization part side, the measurement sensitivity of ions can be improved compared with the past. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a diagram showing the main structure of one embodiment of the mass spectrometer according to the present invention.

[0026] Figure 2It is a schematic diagram of a sample introduction section of the mass spectrometer (when ESI is used) according to the present embodiment.

[0027] Figure 3 It is a schematic diagram of a sample introduction section of the mass spectrometer (when atmospheric pressure MALDI is used) according to the present embodiment.

[0028] Figure 4 This is an example of the configuration of a sample introduction unit of the mass spectrometer (when atmospheric pressure MALDI is used) according to the present embodiment.

[0029] Figure 5 This is a diagram showing a detachable portion of a sample introduction section of the mass spectrometer (when atmospheric pressure MALDI is used) according to the present embodiment.

[0030] Figure 6 These are the results of measuring the temperature of the second ion introduction tube in the comparative example and the example.

[0031] Figure 7 These are the results of measuring the intensities of AngII and Chloroquine ions in Comparative Examples and Examples.

[0032] Figure 8 These are the results of measuring the intensity of ions derived from mouse brain under different conditions of heating temperature of the tip in the examples. DETAILED DESCRIPTION

[0033] Hereinafter, one embodiment of the mass spectrometer according to the present invention will be described with reference to the drawings.

[0034] Figure 1 The main components of the mass spectrometer 1 of this embodiment (when using atmospheric pressure MALDI) are shown. The mass spectrometer 1 of this embodiment includes: an ionization unit, which is an atmospheric pressure MALDI having an ionization chamber 11 set at approximately atmospheric pressure; and a mass analysis unit, which is set in a vacuum chamber 20 and separates and detects ions according to the mass-to-charge ratio. In addition, in the mass spectrometer 1 of this embodiment, ESI (see Figure 2 ) to replace atmospheric pressure MALDI.

[0035] Atmospheric pressure MALDI includes a sample plate holder 13 for placing a sample plate 12, and a sample plate 12 at an observation position ( Figure 1 The position shown by the dashed line in the middle) and the measurement position ( Figure 1The apparatus is provided with a moving mechanism 14 for moving between positions (shown by the solid line in the middle). In addition, it is provided with an optical system such as a laser light source 15, a reflector 16 for reflecting light emitted from the laser light source 15 and irradiating the sample plate 12 placed on the sample plate holder 13, and a lens 17 for focusing the laser light reflected by the reflector 16 on the measurement point on the sample plate. In addition, it is provided with an optical microscope 18 for observing the surface of the sample on the sample plate 12.

[0036] A partition wall 80 is provided between the atmospheric pressure MALDI and the vacuum chamber 20, and a sample introduction part 3 is provided in the partition wall 80. The sample introduction part 3 will be described in detail later.

[0037] In the vacuum chamber 20, a first intermediate vacuum chamber 21, a second intermediate vacuum chamber 22, a third intermediate vacuum chamber 23 and an analysis chamber 24 are provided in order from one side of the ionization chamber 11. Each of these chambers has a multi-stage differential exhaust system structure in which the vacuum degree gradually increases from the first intermediate vacuum chamber 21 to the analysis chamber 24.

[0038] The first intermediate vacuum chamber 21 is provided with an ion lens 211 composed of a plurality of annular electrodes for converging ions generated in the ionization chamber 11 and introduced through the sample introduction unit 3 to the vicinity of the ion optical axis C, which is the central axis of the ion flight direction, and transporting them to the subsequent stage.

[0039] The first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 are separated by a taper 212 having a small hole at the top. The second intermediate vacuum chamber 22 is also provided with an ion guide 221 composed of a plurality of rod electrodes for converging ions near the ion optical axis C and transporting them to the subsequent stage.

[0040] The second intermediate vacuum chamber 22 and the third intermediate vacuum chamber 23 are connected through a small-diameter hole provided in the partition wall between the two. In the third intermediate vacuum chamber 23, a quadrupole mass filter 231 composed of four rod electrodes, a collision cell 232, and an ion lens 234 composed of a plurality of ring electrodes are arranged in order from the side close to the second intermediate vacuum chamber 22. A multipole ion guide 233 composed of a plurality of rod electrodes is arranged inside the collision cell 232. CID gas such as argon gas and nitrogen gas is continuously or intermittently supplied to the inside of the collision cell 232 at an appropriate time.

[0041] The third intermediate vacuum chamber 23 is connected to the analysis chamber 24 through a small-diameter hole provided in the partition wall between the two. In the analysis chamber 24, an ion lens 241 composed of a plurality of annular electrodes, an orthogonal acceleration unit 242, an acceleration electrode 243, a flight tube 244, a reflection electrode 245 and an ion detector 246 are arranged. The orthogonal acceleration unit 242 is composed of a repelling electrode 2421 and an introduction electrode 2422, which are plate-shaped electrodes, respectively. The repelling electrode 2421 and the introduction electrode 2422 are arranged opposite to each other across the flight path of the ions transported by the ion lens 241. An opening for the ions to pass through is provided in the introduction electrode 2422. The acceleration electrode 243 is composed of a plurality of annular electrodes for accelerating the ions whose flight direction is changed by the orthogonal acceleration unit 242. The flight tube 244 is a cylindrical electrode, and the flight space of the ions is defined inside it. The reflection electrode 245 is composed of a plurality of annular electrodes, and a predetermined voltage is applied to each electrode to form a potential gradient that increases toward the potential of the rear stage side. The ions accelerated by the accelerating electrode 243 and flying in the flight space defined in the flight tube 244 return to the flight using the potential gradient. The ion detector 246 detects the ions returning to the flight using the potential gradient formed by the reflecting electrode 245.

[0042] The control unit 5 includes a storage unit 51. The storage unit 51 stores flight time-mass-to-charge ratio information and applied voltage information. The flight time-mass-to-charge ratio information is information that records the time required for ions with various mass-to-charge ratios to fly in the flight space within the analysis chamber 24. In addition, the applied voltage information includes information related to the value of the applied voltage to each electrode provided in the mass spectrometer 1, and information related to the relationship between the applied voltage applied from the first power supply 34 or the second power supply 38 described later and the set temperature. Furthermore, the storage unit 51 also stores a compound database, etc., which includes information related to the measurement conditions (mass-to-charge ratio of the precursor ion, the value of the collision energy, etc.) and analysis methods of each of a plurality of known compounds.

[0043] The control unit 5 also includes a measurement execution unit 52 and an analysis processing unit 53 as functional modules. The measurement execution unit 52 controls the operation of each unit by applying a predetermined voltage to each electrode configured in the mass spectrometer 1 based on the measurement conditions set by the user, thereby performing measurement. The analysis processing unit 53 performs processing such as generating a mass spectrum based on the measurement data. The entity of the control unit 5 is, for example, a general personal computer, and the above-mentioned functional modules are realized by executing a pre-installed dedicated program by a processor. The control unit 5 is also connected to an input unit 6 composed of a keyboard, a mouse, etc. and a display unit 7 composed of a liquid crystal display, etc.

[0044] The mass analysis itself performed by the mass spectrometer 1 of the present embodiment is the same as that in the related art, and therefore will be briefly described below.

[0045] First, a pretreatment is performed by coating the surface of the sample placed on the sample plate 12 with a substance that is easily ionized, i.e., a matrix substance, so that microcrystals of the matrix substance that have taken in the molecules of the sample are formed on the surface of the sample. Next, the sample plate 12 carrying the pretreated sample is placed on the sample plate holder 13, and the sample plate holder 13 is arranged at the measurement position. Then, when the laser is irradiated from the laser light source 15, the microcrystals of the matrix substance are heated, and the sample molecules are separated and ionized. The ions generated by the sample molecules in the ionization chamber 11 pass through the sample introduction part 3 and enter the vacuum chamber 20. The ions entering the vacuum chamber 20 are transported by the ion lens 211 and the ion guide 221, and then incident on the quadrupole mass filter 231. In the quadrupole mass filter 231, ions with a specified mass-to-charge ratio are screened as precursor ions and incident on the collision cell 232. The precursor ions incident on the collision cell 232 collide with the molecules of the CID gas introduced into the collision cell 232 and break, generating product ions. The product ions generated in the collision cell 232 are transported by ion lenses 234 and 241 and incident on the orthogonal acceleration unit 242. The product ions whose flight direction is changed to a substantially orthogonal direction in the orthogonal acceleration unit 242 are accelerated by the acceleration electrode 243, enter the flight space surrounded by the flight tube 244, and are detected by the ion detector 246 after returning to the flight using the potential gradient formed by the reflection electrode 245 located at the end of the flight space.

[0046] The output signals from the ion detector 246 are sequentially stored in the storage unit 51. After the measurement is completed, the analysis processing unit 53 converts the flight time of each ion into a mass-to-charge ratio based on the flight time-mass-to-charge ratio information stored in the storage unit 51, and generates mass spectrum data with mass-to-charge ratio and signal intensity as dual axes.

[0047] The mass spectrometer 1 of the present embodiment is characterized in that the sample introduction section 3 is provided in the partition wall 80 between the ionization chamber 11 and the first intermediate vacuum chamber 21. The sample introduction section 3 will be described below.

[0048] Figure 2 1 is a schematic diagram showing the structure of the sample introduction part 3 when mass analysis is performed on ions generated by ESI. The sample introduction part 3 has a first tube (equivalent to the first ion introduction tube in the present invention) 31, a tube mounting part 32 for mounting the first tube 31, a heating element 33 arranged on the outer periphery of the first tube 31, and a first power supply 34 for supplying power to the heating element 33. The first tube 31 is made of, for example, a stainless steel tube. The central axis of the first tube 31 is orthogonal to the spray direction of the charged droplets from the ESI probe 111, and the ions generated by desolvation of the charged droplets are introduced into the first tube 31 due to the pressure difference between the ionization chamber 11 and the vacuum chamber 20.

[0049] Figure 31 is a schematic diagram showing the structure of the sample introduction part 3 when mass analysis is performed on ions generated by atmospheric pressure MALDI. The sample introduction part 3 includes a first tube 31 mounted on a tube mounting part 32, a tube connecting part 35, and a second tube 36 connected to the first tube 31 through the tube connecting part 35. The second tube 36 also uses a tube made of, for example, stainless steel. The second tube 36 and the tube connecting part 35 can be loaded and unloaded on the first tube 31. In this way, by connecting the second tube 36 to the first tube 31, the ion introduction tube is extended compared to the case of generating ions by ESI, and the inlet end of the second tube 36 is arranged near the sample on the sample plate 12. The first tube 31 and the second tube 36 are equivalent to the second ion introduction tube in the present invention, and the second tube 36 is equivalent to the part of the second ion introduction tube in the present invention that extends from the first ion introduction tube to the ionization part side. Thus, by using an ion introduction tube longer than that used in ESI, the entrance end of the ion introduction tube can be brought closer to the sample surface, and more ions emitted from the sample can be introduced into the mass spectrometer from the ion introduction tube (the second tube 36 and the first tube 31). Here, the ion introduction tube for atmospheric pressure MALDI is formed by connecting the first tube 31 and the second tube 36 by the tube connection part 35, but a single long ion introduction tube can also be used.

[0050] A heating element 33 schematically shown by a heating wire is attached to the outer periphery of the first tube 31, and the first tube 31 is heated by supplying power to the heating element 33 from a first power source 34. Figure 2 and Figure 3 The heating element 33 is schematically shown by a heating line in the figure, but various heating elements that can heat the first tube 31 can be used, for example, a cartridge heater (block heater, etc.), a micro sheath heater, a ceramic coating, etc. can be used as the heating element 33. Alternatively, the first tube 31 can also be heated by irradiation with infrared light or the like.

[0051] A heating element (equivalent to the heating unit in the present invention) 37 schematically shown by a heating wire is also installed on the outer periphery of the second tube 36, and the second tube 36 is heated by supplying power from the second power supply 38 to the heating element 37. The heating element 37 and the second power supply 38 are equivalent to the heating unit in the present invention. Various heating elements can be used to heat the second tube 36. For example, the heating element 37 and the second power supply 38 composed of the various heaters described above, or the second tube 36 can be heated by irradiating infrared light.

[0052] In the mass spectrometer 1 of this embodiment, the heating element 37 for heating the second tube 36 is arranged to heat the end (the end on the ionization chamber 11 side) of the second tube 36. Preferably, the heating element 37 is arranged to surround the tip of the second tube 36 or the periphery near it.

[0053] In conventional mass spectrometers, when mass analysis is performed on ions generated by atmospheric pressure MALDI, the ion introduction tube is simply connected to the first tube to extend the ion introduction tube, but in this case, the ions may not be measured with sufficient sensitivity. Various factors may be considered for this, but since only the first tube is heated and the second tube is not heated and becomes low temperature, it is believed that, for example, the molecules of the matrix substance applied during the pretreatment of the sample are not separated from the ions of the sample molecules, or the ions from the sample lose energy due to collision with the low-temperature gas molecules and adhere to the ion introduction tube and disappear.

[0054] In contrast, in the mass spectrometer 1 of the present embodiment, a heating element 37 is provided to heat the second tube 36. Therefore, not only the first tube 31 but also the second tube 36 is sufficiently heated. As will be described later, referring to the measurement results, by heating the second tube 36, ions can be detected with higher sensitivity than before.

[0055] Next, the measurement result that the detection sensitivity of ions is improved by heating the second tube 36, which is confirmed in the mass spectrometer 1 of the present embodiment, is described. Figure 4 As shown, a first tube mounting component 41 is arranged on the outer periphery of the first tube 31, and a second tube mounting component 42 is arranged on the outer periphery of the second tube 36. Both the first tube mounting component 41 and the second tube mounting component 42 are made of conductive stainless steel. The first tube mounting component 41 and the second tube mounting component 42 can be installed and removed. The first tube mounting component 41 is connected to the first power source 34. When the first power source 34 is energized to the first tube mounting component 41 and the first tube 31, the first tube 31 having a large resistance is heated. Inside the second tube mounting component 42, a cartridge heater 43 is arranged along the outer periphery of the second tube 36. When a voltage is applied to the cartridge heater 43 from the second power source 38, the cartridge heater 43 is heated and the second tube 36 is heated.

[0056] exist Figure 4 In the sample introduction section 3 of the configuration example, it is possible to load and unload Figure 5 The parts shown in the figure (tube connection part 35, second tube 36, second tube mounting member 42 and cartridge heater 43). Therefore, when switching between ESI and atmospheric pressure MALDI, only the installation and removal Figure 5 The components shown are sufficient, and there is no need to remove the first pipe 31 mounted to the partition wall 80 via the pipe mounting portion 32 .

[0057] In addition, Figure 4In the illustrated configuration example, the second tube 36 and the cartridge heater 43 (the second tube mounting member 42 including the cartridge heater 43) are separately configured, and both can be attached and detached. Therefore, when the sample component adheres to the inside of the second tube 36 or when the second tube 36 is clogged, only the second tube 36 can be removed for cleaning or replacement. In addition, when the cartridge heater 43 fails such as disconnection, only the cartridge heater 43 can be replaced. As a result, the cost can be reduced compared to the case of replacing the second tube 36 and the cartridge heater 43 (the second tube mounting member 42 including the cartridge heater 43) which are integrated.

[0058] First, as a comparative example (without front end heating), the first tube 31 was heated to 250° C. by powering from the first power source 34, and the temperature of the second tube 36 was measured. Furthermore, as an example (with front end heating), in addition to heating the first tube 31, the second tube 36 was heated to 450° C. by the cartridge heater 43, and the temperature of the second tube 36 was measured. In addition, the length of the second tube 36 used in these measurements was 50 mm.

[0059] like Figure 6 As shown in the measurement results, in the embodiment (with front end heating), the entire second tube 36 becomes higher temperature than the comparative example. In particular, the front end portion of the second tube 36 on the ionization chamber side becomes higher temperature than the comparative example (about 50°C).

[0060] In addition, for the comparative examples and the examples, the ions generated by AngII (angiotensin II) and Chloroquine (chloroquine) were measured respectively. Figure 7 As shown, for any ion, the measured intensity of the example with front-end heating is improved compared with the comparative example without front-end heating.

[0061] Furthermore, a measurement was performed to investigate the relationship between the heating temperature and the measured intensity when the front end was heated as in the example. In this measurement, a slice of mouse brain (mouse brain) was used as a sample, and the ion of m / z=798.54 (phosphatidylcholine (34:1)) generated from the slice was measured.

[0062] like Figure 8 As shown in FIG. 1 , the maximum heating temperature of the front end in the measurement (the heating temperature of the second tube 36) is about 430°C. At least until this temperature, the higher the heating temperature, the higher the measurement intensity of the ions. The heat resistance of the sample needs to be considered, but it is believed that at least before exceeding 400°C, the higher the second tube 36 is heated, the higher the measurement sensitivity of the ions. In addition, although it depends on the material of the second tube 36, it is appropriate to set the upper limit of the heating temperature of the second tube 36 to about 500°C in consideration of heat resistance.

[0063] In the above-described embodiment, the configuration of the device used for actual measurement is merely an example and can be appropriately changed in accordance with the gist of the present invention.

[0064] In the above-mentioned embodiments and examples, atmospheric pressure MALDI and ESI are used as ion sources, but other laser ion sources (such as SALDI) may be used instead of atmospheric pressure MALDI. In addition, APCI or DUIS having both ESI and APCI may be used instead of ESI.

[0065] In the above-mentioned embodiments and examples, the ion introduction tube for atmospheric pressure MALDI is formed by connecting the second tube 36 as an extension tube to the ion introduction tube for ESI, that is, the first tube 31. However, an ion introduction tube longer than the ion introduction tube for ESI can also be used as the ion introduction tube for atmospheric pressure MALDI.

[0066] In addition, in the above-mentioned embodiment, the configuration of heating the first tube 31 and the second tube 36 is described, but it is also effective to provide a means for suppressing heat dissipation in addition to the heating unit. Specifically, a heat insulating material may be wound around the outer periphery of the first tube 31 and / or the second tube 36, or a reflector that reflects heat radiation from the first tube 31 and / or the second tube 36 may be arranged in a manner that surrounds the first tube 31 and / or the second tube 36.

[0067] [plan]

[0068] The above-described exemplary embodiments are specific examples of the following aspects, which are self-evident to those skilled in the art.

[0069] (Item 1)

[0070] One embodiment of the present invention is a mass spectrometer, which is selectively equipped with a first ion source and a second ion source as an ionization unit, wherein the first ion source sprays a liquid sample under an atmospheric pressure atmosphere to ionize, and the second ion source irradiates a sample with a laser under an atmospheric pressure atmosphere to ionize, and the mass spectrometer comprises:

[0071] A mass analysis unit is provided in a vacuum chamber connected to the ionization unit via a partition wall, and separates and detects ions generated by the ionization unit according to a mass-to-charge ratio;

[0072] a second ion introduction tube, which is provided through the partition wall and introduces ions generated by the ionization section into the vacuum chamber, the second ion introduction tube being longer than the first ion introduction tube used when the first ion source is used and being used when the second ion source is used;

[0073] The heating unit heats a portion of the second ion introduction tube extending from the first ion introduction tube to the ionization unit side.

[0074] The mass spectrometer involved in the first item is a mass spectrometer that selectively has a first ion source and a second ion source as an ionization unit, the first ion source spraying a liquid sample under an atmospheric pressure atmosphere to ionize, and the second ion source irradiating a sample mixed or coated with a matrix substance under an atmospheric pressure atmosphere to ionize by laser. The first ion source that sprays a liquid sample to ionize is, for example, ESI, APCI, or a DUIS that has both. In addition, the second ion source that irradiates a sample mixed or coated with a matrix substance under an atmospheric pressure atmosphere to ionize by laser is an atmospheric pressure MALDI.

[0075] If the ion introduction tube used in ESI and APCI is directly used when using atmospheric pressure MALDI, the distance from the entrance end of the ion introduction tube to the measurement point becomes longer, and the efficiency of ion introduction into the ion introduction tube becomes worse. Therefore, in the mass spectrometer involved in the first item, when using the second ion source, a second ion introduction tube that is longer than the first ion introduction tube used when using the first ion source is used. According to the discovery obtained by the inventors, the reason why ions could not be measured with sufficient sensitivity when using the second ion introduction tube in the past was that the portion of the second ion introduction tube extending from the first ion introduction tube was not heated and became low temperature. In the mass spectrometer involved in the first item, by using a heating unit to heat the portion of the second ion introduction tube extending from the first ion introduction tube, the measurement sensitivity of ions can be improved compared with the past.

[0076] (Item 2)

[0077] The mass spectrometer according to item 2 is the mass spectrometer according to item 1,

[0078] The second ion introduction tube includes the first ion introduction tube and an extension tube connected to the first ion introduction tube.

[0079] (Item 3)

[0080] The mass spectrometer according to item 3 is the mass spectrometer according to item 1,

[0081] The second ion introduction tube is composed of one tube.

[0082] The second ion introduction tube in the mass spectrometer of item 1 may be a single ion introduction tube having a length such that the end portion on the ionization portion side is located at the laser irradiation position close to the sample surface, as in the mass spectrometer of item 3, or may include a first ion introduction tube and a second tube detachably connected to the first ion introduction tube, as in the mass spectrometer of item 2. In the mass spectrometer of item 2, the second ion introduction tube can be simply constructed by connecting an extension tube to a state where the first ion introduction tube penetrating the partition wall is installed.

[0083] (Item 4)

[0084] The mass spectrometer according to item 4 is the mass spectrometer according to any one of items 1 to 3,

[0085] The heating unit includes a heating element that is provided so as to surround the second ion introduction tube and generates heat when electricity is supplied thereto.

[0086] In the mass spectrometer of item 4, by heating the ion introduction tube with the heating element that generates heat when energized, the second ion introduction tube can be heated to a higher temperature, thereby improving the measurement sensitivity of ions.

[0087] (Item 5)

[0088] The mass spectrometer according to item 5 is the mass spectrometer according to item 4,

[0089] The heating element and the second ion introduction tube are configured as separate bodies and can be attached to and detached from each other.

[0090] In the mass spectrometer according to item 5, when the sample component is attached to the inside of the second ion introduction tube or the second ion introduction tube is clogged, only the second ion introduction tube can be removed for cleaning or replacement. In addition, when the heating element fails such as disconnection, only the heating element can be replaced. Therefore, compared with the case of replacing both the second ion introduction tube and the heating element, the cost can be reduced.

[0091] Description of Reference Numerals

[0092] 1. Quality analysis device

[0093] 11. Ionization chamber

[0094] 111 ESI probe

[0095] 12 Sample Plate

[0096] 13 Sample plate holder

[0097] 14 Mobile mechanism

[0098] 15. Laser light source

[0099] 16 Reflector

[0100] 17 Lens

[0101] 18. Optical Microscope

[0102] 20 Vacuum chamber

[0103] 21. 1st intermediate vacuum chamber

[0104] 211 Ion Lens

[0105] 212 cone body

[0106] 22. Second intermediate vacuum chamber

[0107] 221 Ion Guide

[0108] 23 The third intermediate vacuum chamber

[0109] 231 Quadrupole Mass Filter

[0110] 232 Collision Cell

[0111] 233 Multipole ion guide

[0112] 234 Ion Lens

[0113] 24 Analysis Room

[0114] 241 Ion Lens

[0115] 242 Orthogonal Acceleration Unit

[0116] 2421 Repulsion Electrode

[0117] 2422 Introduction of electrodes

[0118] 243 Accelerating Electrode

[0119] 244 Flight Tube

[0120] 245 Reflection Electrode

[0121] 246 Ion Detector

[0122] 3. Sample introduction section

[0123] 31 No.1 Tube

[0124] 32 Pipe installation part

[0125] 33 Heating element

[0126] 34 1st Power Supply

[0127] 35 Pipe connection

[0128] 36 No. 2 Tube

[0129] 37 Heating element

[0130] 38 Second power supply

[0131] 41 1st pipe mounting parts

[0132] 42 2nd pipe mounting parts

[0133] 43 Cartridge Heater

[0134] 5. Control Unit

[0135] 51 Storage

[0136] 52 Measurement execution unit

[0137] 53 Analysis Processing Unit

[0138] 6 Input section

[0139] 7 Display

[0140] 80 partition wall

[0141] C ion optical axis.

Claims

1. A mass spectrometer, wherein a first ion source and a second ion source are selectively installed as ionization units, wherein the first ion source sprays a liquid sample under an atmospheric pressure atmosphere to ionize the sample, and the second ion source irradiates the sample with a laser under an atmospheric pressure atmosphere to ionize the sample, the mass spectrometer comprising: A mass analysis unit is provided in a vacuum chamber connected to the ionization unit via a partition wall, and separates and detects ions generated by the ionization unit according to a mass-to-charge ratio; a second ion introduction tube, which is provided through the partition wall and introduces ions generated by the ionization section into the vacuum chamber, the second ion introduction tube being longer than the first ion introduction tube used when the first ion source is used and being used when the second ion source is used; The heating unit heats a portion of the second ion introduction tube extending from the first ion introduction tube to the ionization unit side.

2. The mass spectrometer according to claim 1, wherein: The second ion introduction tube includes the first ion introduction tube and an extension tube connected to the first ion introduction tube.

3. The mass spectrometer according to claim 1, wherein: The second ion introduction tube is composed of one tube.

4. The mass spectrometer according to claim 1, wherein: The heating unit includes a heating element that is provided so as to surround the second ion introduction tube and generates heat when electricity is supplied thereto.

5. The mass spectrometer according to claim 4, wherein: The heating element and the second ion introduction tube are configured as separate bodies and can be attached to and detached from each other.

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