Quality analysis device

Abstract

Provided is a mass spectrometer (1) in which a first ion source (12) to (17) that atomizes a liquid sample under an atmospheric pressure to ionize the liquid sample and a second ion source (111) that emits laser beam to the sample to ionize the sample are attached alternatively as an ionization section, the mass spectrometer (1) being further provided with: a mass analysis section (231), (242) to (246) which is disposed in a vacuum chamber connected to the ionization section through a partitioning wall and separates and detects ions in accordance with mass-to-charge ratios thereof; a second ion introduction tube (31), (36) which is longer than a first ion introduction tube and is used when the second ion source is used, in which the first ion introduction tube is disposed through the partitioning wall and through which ions are introduced into the vacuum chamber and us used when the first ion source is used; and a heating section (37), (38) which heats a part of the second ion introduction tube which extends from the first ion introduction tube toward the ionization section side.

Description

[Technical Field]

[0001] The present invention relates to a mass spectrometer that uses an ion source that generates ions by irradiating a sample with laser light in an atmospheric pressure environment. [Background technology]

[0002] Mass spectrometers equipped with an ionization unit that generates ions of target substances by electrospray ionization (ESI) are used to identify and quantify target substances contained in liquid samples. In ESI, the liquid sample is charged and sprayed into an ionization chamber at approximately atmospheric pressure, and the ions are then introduced into a mass analysis unit in a vacuum chamber via an ion introduction tube. The ion introduction tube is positioned so as to penetrate the partition between the ionization chamber and the vacuum chamber, and heating the ion introduction tube promotes desolvation of ions, thereby increasing ion generation efficiency.

[0003] Furthermore, mass spectrometry using a mass spectrometer equipped with MALDI is being carried out to measure target substances contained in biological samples, etc. (For example, Patent Document 1). MALDI is an ion source that ionizes a sample by the matrix-assisted laser desorption / ionization method.

[0004] There are two types of MALDI: atmospheric pressure MALDI, which ionizes samples in an atmospheric pressure environment, and vacuum MALDI, which ionizes samples in a vacuum environment. Mass spectrometers with atmospheric pressure MALDI have an ionization section (atmospheric pressure MALDI) that operates at atmospheric pressure, and a mass analysis section located in a vacuum chamber that separates and detects ions according to their mass-to-charge ratio.

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

[0006] First, a sample surface placed on a sample plate is pretreated by applying a matrix substance, which is an easily ionized substance, to form microcrystals of the matrix substance that incorporate the sample molecules on the sample surface. When the sample plate with the pretreated sample placed on it is set in a predetermined position in the MALDI and laser light is irradiated onto the sample surface, the microcrystals of the matrix substance present on the surface are heated, and the sample molecules incorporated into the microcrystals are desorbed and ionized.

[0007] Ions generated from sample molecules are introduced into the inlet end (ion inlet) of the ion introduction tube and pass through the ion introduction tube to enter the mass analysis section. The ions that enter the mass analysis section are separated according to their mass-to-charge ratio and detected by an ion detector. By correlating the signal intensities sequentially output from the ion detector with the mass-to-charge ratio of the ions, 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 ESI and atmospheric pressure MALDI use different ionization methods, they can use the same mass analyzer. However, in atmospheric pressure MALDI, mirrors for reflecting the light irradiating the sample surface and lenses for focusing the light are placed in front of the sample. Therefore, in atmospheric pressure MALDI, the sample is usually located farther from the vacuum chamber than in ESI. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Patent Publication No. 2021-196303 [Non-patent literature]

[0010] [Non-Patent Document 1] "Imaging One-Stop Application: From Evaluation of the Physical Properties of Administered Drugs to Metabolomics by Distribution and Quantitation of Drugs and Metabolites", [online], Shimadzu Corporation, [Retrieved September 7, 2023], Internet<URL:https: / / www.an.shimadzu.co.jp / bio / imaging / index.htm> Summary of the Invention [Problem to be solved by the invention]

[0011] If the ion introduction tube used in ESI is used as is, the distance from the sample to the inlet of the ion introduction tube becomes long, resulting in poor ion uptake efficiency into the ion introduction tube. Therefore, when ions are generated by atmospheric pressure MALDI, for example, an extension tube is connected to the ion introduction tube used to introduce ions generated by ESI into a vacuum chamber, and the inlet end of the ion introduction tube is positioned near the measurement point. However, it has been found that when an extension tube is connected to the ion introduction tube used in ESI to lengthen the tube and introduce ions generated by atmospheric pressure MALDI into a vacuum chamber, it may not be possible to measure the ions with sufficient sensitivity.

[0012] The problem to be solved by the present invention is to improve the measurement sensitivity of ions in a mass spectrometer that uses an ion source that generates ions by irradiating a sample with laser light in an atmospheric pressure environment. [Means for solving the problem]

[0013] The present invention, which has been made to solve the above problems, is a mass spectrometer in which a first ion source that sprays and ionizes a liquid sample in an atmospheric pressure environment and a second ion source that ionizes the sample by irradiating it with laser light in an atmospheric pressure environment are alternatively installed as an ionization unit, a mass analysis unit provided in a vacuum chamber connected to the ionization unit via a partition wall, which separates and detects ions generated in the ionization unit according to their mass-to-charge ratios; a second ion introduction tube that is provided through the partition wall and introduces ions generated in the ionization unit into the vacuum chamber, the second ion introduction tube being longer than the first ion introduction tube that is used when the first ion source is in use and that is used when the second ion source is in use; a heating unit that heats a portion of the second ion introduction tube that extends from the first ion introduction tube toward the ionization unit; Equipped with. [Effects of the Invention]

[0014] The first ion source that sprays and ionizes a liquid sample is, for example, an ESI, an atmospheric pressure chemical ionization (APCI), or a dual ion source (DUIS) equipped with both. The second ion source that ionizes a sample by irradiating it with laser light in an atmospheric pressure environment is, for example, an atmospheric pressure MALDI or a surface-assisted laser desorption ionization source (SALDI).

[0015] If an ion introduction tube used in ESI or APCI is used in atmospheric pressure MALDI or the like, the distance from the inlet end of the ion introduction tube to the measurement point becomes long, resulting in poor ion introduction efficiency into the ion introduction tube. Therefore, in the present invention, when using a 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 findings of the present inventors, the reason why ions could not be measured with sufficient sensitivity when using a second ion introduction tube in the past was that the portion of the second ion introduction tube extending from the first ion introduction tube toward the ionization section was not heated and remained at a low temperature. In the mass spectrometer according to the present invention, the portion of the second ion introduction tube extending from the first ion introduction tube toward the ionization section is heated by a heating section, thereby improving ion measurement sensitivity compared to conventional methods. [Brief explanation of the drawings]

[0016] [Figure 1] 1 is a diagram showing the configuration of a main part of an embodiment of a mass spectrometer according to the present invention; [Figure 2]FIG. 2 is a schematic diagram of the sample introduction section of the mass spectrometer of this embodiment (when using ESI). [Figure 3] FIG. 2 is a schematic diagram of the sample introduction section of the mass spectrometer of the present embodiment (when atmospheric pressure MALDI is used). [Figure 4] 1 shows an example of the configuration of the sample introduction section of the mass spectrometer of this embodiment (when atmospheric pressure MALDI is used). [Figure 5] FIG. 2 is a diagram showing a detachable portion of the sample introduction section of the mass spectrometer of the present embodiment (when atmospheric pressure MALDI is used). [Figure 6] 10 shows the results of measuring the temperature of the second iontophoresis tube in the comparative example and the example. [Figure 7] The results of measuring the ionic strength of Ang II and chloroquine in the comparative example and the example. [Figure 8] 1 shows the results of measuring the intensity of ions derived from mouse brain under different heating temperatures of the tip in an example. DETAILED DESCRIPTION OF THE INVENTION

[0017] An embodiment of a mass spectrometer according to the present invention will be described below with reference to the drawings.

[0018] 1 shows the overall configuration of the main components of a mass spectrometer 1 (using atmospheric pressure MALDI) according to this embodiment. The mass spectrometer 1 of this embodiment includes an ionization section having atmospheric pressure MALDI installed in an ionization chamber 11 that is at approximately atmospheric pressure, and a mass analysis section installed in a vacuum chamber 20 that separates and detects ions according to their mass-to-charge ratio. Furthermore, in the mass spectrometer 1 of this embodiment, instead of atmospheric pressure MALDI, ESI (see FIG. 2) can be used, which similarly sprays and ionizes a liquid sample in an atmospheric pressure environment (electrospray ionization).

[0019] The atmospheric pressure MALDI system includes a sample plate holder 13 on which a sample plate 12 is placed, and a moving mechanism 14 that moves the sample plate 12 between an observation position (the position indicated by the dashed line in FIG. 1) and a measurement position (the position indicated by the solid line in FIG. 1). It also includes an optical system including a laser light source 15, a mirror 16 that reflects light emitted from the laser light source 15 and irradiates the sample plate 12 placed on the sample plate holder 13, and a lens 17 that focuses the laser light reflected by the mirror 16 onto a measurement point on the sample plate. It also includes an optical microscope 18 for observing the surface of the sample on the sample plate 12.

[0020] A partition wall 80 is provided between the atmospheric pressure MALDI and the vacuum chamber 20, and the partition wall 80 is provided with a sample introduction part 3. Details of the sample introduction part 3 will be described later.

[0021] Within 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 this order from the ionization chamber 11 side. Each of these chambers has a multi-stage differential pumping system configuration in which the degree of vacuum gradually increases from the first intermediate vacuum chamber 21 to the analysis chamber 24.

[0022] An ion lens 211 made up of multiple ring electrodes is arranged in the first intermediate vacuum chamber 21 to focus the ions generated in the ionization chamber 11 and introduced through the sample introduction section 3 in the vicinity of the ion optical axis C, which is the central axis of the ion flight direction, and transport them to the subsequent stage.

[0023] The first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 are separated by a skimmer 212 having a small hole at the top. The second intermediate vacuum chamber 22 also has an ion guide 221 made up of multiple rod electrodes for focusing ions near the ion optical axis C and transporting them to the subsequent stage.

[0024] The second intermediate vacuum chamber 22 and the third intermediate vacuum chamber 23 are connected by a small-diameter hole provided in the partition between them. In the third intermediate vacuum chamber 23, from the side closest to the second intermediate vacuum chamber 22, there are arranged a quadrupole mass filter 231 composed of four rod electrodes, a collision cell 232, and an ion lens 234 composed of multiple ring electrodes. Inside the collision cell 232, there is arranged a multipole ion guide 233 composed of multiple rod electrodes. A CID gas such as argon or nitrogen is supplied continuously or intermittently into the collision cell 232 at appropriate timing.

[0025] The third intermediate vacuum chamber 23 and the analysis chamber 24 are connected by a small-diameter hole in the partition between them. The analysis chamber 24 contains an ion lens 241 composed of multiple ring electrodes, an orthogonal acceleration unit 242, an acceleration electrode 243, a flight tube 244, a reflectron electrode 245, and an ion detector 246. The orthogonal acceleration unit 242 is composed of a pusher electrode 2421 and a pull-in electrode 2422, which are plate-shaped electrodes arranged opposite each other across the flight path of ions transported by the ion lens 241. The pull-in electrode 2422 has an opening for allowing ions to pass through. The acceleration electrode 243 is composed of multiple ring electrodes for accelerating ions whose flight direction has been changed by the orthogonal acceleration unit 242. The flight tube 244 is a cylindrical electrode that defines a flight space for ions. The reflectron electrode 245 is composed of multiple ring electrodes, and a predetermined voltage is applied to each electrode to form a potential gradient in which the potential increases toward the downstream side. Ions accelerated by the accelerating electrode 243 and flying through the flight space defined inside the flight tube 244 are turned around by this potential gradient. The ion detector 246 detects the ions that have turned around due to the potential gradient formed by the reflectron electrode 245.

[0026] The control unit 5 includes a memory unit 51. The memory unit 51 stores time-of-flight-mass-to-charge ratio information and applied voltage information. The time-of-flight-mass-to-charge ratio information is information describing the time required for ions having various mass-to-charge ratios to fly through the flight space within the analysis chamber 24. The applied voltage information includes information regarding the value of the voltage applied to each electrode provided in the mass spectrometer 1, and information regarding the relationship between the applied voltage from the first power supply 34 and the second power supply 38 (described below) and the set temperature. The memory unit 51 also stores a compound database containing information regarding the measurement conditions (mass-to-charge ratio of the precursor ion, collision energy value, etc.) and analysis methods for each of a plurality of known compounds.

[0027] The control unit 5 also includes, as functional blocks, a measurement execution unit 52 and an analysis processing unit 53. The measurement execution unit 52 executes measurements by controlling the operation of each unit, for example by applying a predetermined voltage to each electrode arranged in the mass spectrometer 1 based on measurement conditions set by the user. The analysis processing unit 53 performs processes such as generating a mass spectrum from measurement data. The actual entity of the control unit 5 is, for example, a general personal computer, and the above functional blocks are realized by executing a dedicated program pre-installed in the processor. The control unit 5 is also connected to an input unit 6 consisting of a keyboard, mouse, etc., and a display unit 7 consisting of a liquid crystal display, etc.

[0028] The mass analysis itself performed by the mass spectrometer 1 of this embodiment is the same as that performed in the conventional mass spectrometer, and will be briefly described below.

[0029] First, a pretreatment is performed by applying a matrix substance, which is an easily ionized substance, to the surface of a sample placed on the sample plate 12, thereby forming microcrystals of the matrix substance that incorporate sample molecules on the sample surface. Next, the sample plate 12 with the pretreated sample placed thereon is placed on the sample plate holder 13, and the sample plate holder 13 is positioned at the measurement position. Laser light is then irradiated from the laser light source 15, heating the microcrystals of the matrix substance, causing the sample molecules to desorb and ionize. Ions generated from the sample molecules in the ionization chamber 11 enter the vacuum chamber 20 through the sample introduction section 3. After entering the vacuum chamber 20, the ions are transported by the ion lens 211 and ion guide 221 and then enter the quadrupole mass filter 231. In the quadrupole mass filter 231, ions with a predetermined mass-to-charge ratio are selected as precursor ions and enter the collision cell 232. The precursor ions entering the collision cell 232 collide with molecules of the CID gas introduced into the collision cell 232 and are fragmented to generate product ions. The product ions generated in the collision cell 232 are transported by ion lenses 234 and 241 and enter 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 an acceleration electrode 243, enter a flight space surrounded by a flight tube 244, and after flying back and forth due to the potential gradient formed by a reflectron electrode 245 located at the end of the flight tube, are detected by an ion detector 246.

[0030] The output signals from the ion detector 246 are sequentially stored in the memory unit 51. After the measurement is completed, the analysis processing unit 53 converts the time of flight of each ion into a mass-to-charge ratio based on the time-of-flight-mass-to-charge ratio information stored in the memory unit 51, and generates mass spectrum data with the mass-to-charge ratio and signal intensity as two axes.

[0031] The mass spectrometer 1 of this embodiment is characterized by the configuration of the sample introduction section 3 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.

[0032] 2 is a schematic diagram showing the configuration of the sample introduction unit 3 when mass spectrometry is performed on ions generated by ESI. The sample introduction unit 3 has a first tube 31 (corresponding to the first ion introduction tube in this invention), a tube attachment unit 32 to which the first tube 31 is attached, a heating element 33 arranged on the outer periphery of the first tube 31, and a first power supply 34 that supplies power to the heating element 33. The first tube 31 is made of, for example, stainless steel. The central axis of the first tube 31 is perpendicular to the spray direction of the charged droplets from the ESI probe 111, and ions generated by desolvation from the charged droplets are drawn into the first tube 31 due to the pressure difference between the ionization chamber 11 and the vacuum chamber 20.

[0033] FIG. 3 is a schematic diagram showing the configuration of the sample introduction unit 3 when mass analyzing ions generated by atmospheric pressure MALDI. The sample introduction unit 3 includes a first tube 31 attached to a tube mounting unit 32, a tube connection unit 35, and a second tube 36 connected to the first tube 31 via the tube connection unit 35. The second tube 36 is also made of, for example, stainless steel. The second tube 36 and the tube connection unit 35 are detachable from the first tube 31. By connecting the second tube 36 to the first tube 31 in this manner, the ion introduction tube is made longer than when ions are generated by ESI, and the inlet end of the second tube 36 is positioned near the sample on the sample plate 12. The first tube 31 and the second tube 36 correspond to the second ion introduction tube in this invention, and the second tube 36 corresponds to the portion of the second ion introduction tube that extends from the first ion introduction tube toward the ionization unit in this invention. In this way, by using a longer ion introduction tube than when using ESI, the inlet end of the ion introduction tube can be brought closer to the sample surface, allowing a larger number of ions emitted from the sample to be introduced into the mass spectrometer from the ion introduction tube (second tube 36 and first tube 31). Here, the ion introduction tube for atmospheric pressure MALDI is configured by connecting first tube 31 and second tube 36 with tube connector 35, but a single long ion introduction tube may also be used.

[0034] A heating element 33, schematically represented by a heater 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 supply 34. Although a heater wire is schematically shown in Figures 2 and 3, various devices capable of heating the first tube 31 can be used, and for example, a cartridge heater (such as a block heater), a microsheath heater, or a ceramic coating can be used as the heating element 33. Alternatively, the first tube 31 may be heated by irradiation with infrared light or the like.

[0035] Similarly, a heating element (corresponding to the heating section in the present invention) 37, schematically shown as a heater wire, is attached to the outer periphery of the second tube 36, and the second tube 36 is heated by supplying power to the heating element 37 from a second power source 38. The heating element 37 and the second power source 38 correspond to the heating section in the present invention. Various methods can be used to heat the second tube 36; for example, the second tube 36 can be heated using the heating element 37 and the second power source 38 made up of the various heaters described above, or by irradiating it with infrared light.

[0036] In the mass spectrometer 1 of this embodiment, the heating element 37 that heats the second tube 36 is arranged so as to heat the end (the end on the ionization chamber 11 side) of the second tube 36. Preferably, the heating element 37 is arranged so as to surround the outer periphery of the tip of the second tube 36 or the vicinity thereof.

[0037] In conventional mass spectrometers, when performing mass analysis of ions generated by atmospheric pressure MALDI, the ion introduction tube was simply extended by connecting a second tube to the first tube, but in this case, ions could not always be measured with sufficient sensitivity. There are several possible reasons for this, including the fact that only the first tube is heated, while the second tube is not, remaining at a low temperature. For example, it is thought that the molecules of the matrix material applied during sample pretreatment do not desorb from the ions of the sample molecules, or that the ions from the sample lose energy through collisions with low-temperature gas molecules, adhering to the ion introduction tube and disappearing.

[0038] In contrast, the mass spectrometer 1 of this embodiment is provided with a heating element 37 that heats 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 with reference to measurement results, by heating the second tube 36, ions can be detected with higher sensitivity than conventional methods.

[0039] Next, we will explain the results of measurements confirming that heating the second tube 36 improves ion detection sensitivity in the mass spectrometer 1 of this embodiment. Here, as shown in FIG. 4 , a first tube mounting member 41 is arranged around the outer periphery of the first tube 31, and a second tube mounting member 42 is arranged around the outer periphery of the second tube 36. Both the first tube mounting member 41 and the second tube mounting member 42 are made of electrically conductive stainless steel. The first tube mounting member 41 and the second tube mounting member 42 are detachable. A first power supply 34 is connected to the first tube mounting member 41. When electricity is applied from the first power supply 34 to the first tube mounting member 41 and the first tube 31, the first tube 31, which has a high electrical resistance, generates heat. A cartridge heater 43 is arranged inside the second tube mounting member 42 and along the outer periphery of the second tube 36. When a voltage is applied to the cartridge heater 43 from the second power supply 38, the cartridge heater 43 generates heat, thereby heating the second tube 36.

[0040] 4, the components shown in Fig. 5 (tube connection part 35, second tube 36, second tube mounting member 42, and cartridge heater 43) can be attached and detached. Therefore, when switching between ESI and atmospheric pressure MALDI, it is only necessary to attach and detach the components shown in Fig. 5, and there is no need to remove first tube 31 attached to partition wall 80 by tube mounting part 32.

[0041] In addition, in the configuration example shown in Figure 4, the second tube 36 and the cartridge heater 43 (including the second tube mounting member 42) are configured as separate bodies, and both are detachable. Therefore, if sample components adhere to the inside of the second tube 36 or if the second tube 36 becomes clogged, only the second tube 36 can be removed and cleaned or replaced. Also, if a malfunction occurs in the cartridge heater 43, such as a wire break, only the cartridge heater 43 can be replaced. This reduces costs compared to replacing the integrated second tube 36 and cartridge heater 43 (including the second tube mounting member 42).

[0042] First, as a comparative example (without tip heating), the first tube 31 was heated to 250°C by applying current from the first power source 34, and the temperature of the second tube 36 was measured. Also, as an example (with tip 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. The length of the second tube 36 used in these measurements was 50 mm.

[0043] 6, in the example (with tip heating), the entire second tube 36 is at a higher temperature than in the comparative example. In particular, the tip of the second tube 36 on the ionization chamber side is at a higher temperature by more than 200°C compared to the comparative example (approximately 50°C).

[0044] Furthermore, the ions generated from Ang II (angiotensin II) and chloroquine were measured for each of the comparative example and the example. As shown in Figure 7, the measured intensity for each ion was higher in the example in which tip heating was performed than in the comparative example in which tip heating was not performed.

[0045] Furthermore, measurements were also carried out to examine the relationship between the heating temperature and the measurement intensity when tip heating was performed as in the example. In these measurements, mouse brain slices (mouse brain) were used as samples, and the ion m / z = 798.54 (Phosphatidylcholine (34:1)) generated from the slices was measured.

[0046] As shown in Figure 8, the maximum heating temperature of the tip (heating temperature of second tube 36) in this measurement was approximately 430°C, and the measured ion intensity increased as the heating temperature was increased, at least up to this temperature. Although it is necessary to consider the heat resistance of the sample, it is thought that the higher the second tube 36 is heated to, the better the ion measurement sensitivity will be, at least up to 400°C or more. Note that, although this depends on the material of second tube 36, considering heat resistance and other factors, it is appropriate to set the upper limit of the heating temperature of second tube 36 to approximately 500°C.

[0047] The above embodiment and the configuration of the device used in the actual measurements are merely examples, and can be modified as appropriate in accordance with the spirit of the present invention.

[0048] In the above embodiments and examples, atmospheric pressure MALDI and ESI were used as ion sources, but other laser ion sources (e.g., SALDI) can be used instead of atmospheric pressure MALDI. Also, instead of ESI, APCI or a DUIS equipped with both ESI and APCI can be used.

[0049] In the above-described embodiments and examples, an ion introduction tube for atmospheric pressure MALDI is constructed by connecting the second tube 36 as an extension tube to the first tube 31, which is an ion introduction tube for ESI. However, a single ion introduction tube that is longer than the ion introduction tube for ESI may also be used as the ion introduction tube for atmospheric pressure MALDI.

[0050] Furthermore, in the above embodiment, a configuration for heating the first pipe 31 and the second pipe 36 has been described, but it is also effective to provide a means for suppressing heat radiation in addition to a heating unit. Specifically, a heat insulating material may be wrapped around the outer periphery of the first pipe 31 and / or the second pipe 36, or a reflector that reflects heat radiation from the first pipe 31 and / or the second pipe 36 may be disposed so as to surround the first pipe 31 and / or the second pipe 36.

[0051] [Aspect] It will be apparent to those skilled in the art that the above-described exemplary embodiments are examples of the following aspects.

[0052] (Section 1) One aspect of the present invention is a mass spectrometer in which a first ion source that sprays and ionizes a liquid sample in an atmospheric pressure environment and a second ion source that ionizes the sample by irradiating it with laser light in an atmospheric pressure environment are alternatively installed as an ionization unit, a mass analysis unit provided in a vacuum chamber connected to the ionization unit via a partition wall, which separates and detects ions generated in the ionization unit according to their mass-to-charge ratios; a second ion introduction tube that is provided through the partition wall and introduces ions generated in the ionization unit into the vacuum chamber, the second ion introduction tube being longer than the first ion introduction tube that is used when the first ion source is in use and that is used when the second ion source is in use; a heating unit that heats a portion of the second ion introduction tube that extends from the first ion introduction tube toward the ionization unit; Equipped with.

[0053] The mass spectrometer according to paragraph 1 is a mass spectrometer that is alternatively equipped as an ionization unit with a first ion source that sprays and ionizes a liquid sample under atmospheric pressure, and a second ion source that ionizes a sample mixed with or coated with a matrix substance under atmospheric pressure by irradiating the sample with laser light. The first ion source that sprays and ionizes a liquid sample is, for example, a DUIS equipped with ESI, APCI, or both. Furthermore, the second ion source that ionizes a sample mixed with or coated with a matrix substance under atmospheric pressure by irradiating the sample with laser light is atmospheric pressure MALDI.

[0054] If an ion introduction tube used in ESI or APCI is used in atmospheric pressure MALDI without modification, the distance from the inlet end of the ion introduction tube to the measurement point becomes long, resulting in poor ion introduction efficiency into the ion introduction tube. Therefore, in the mass spectrometer according to paragraph 1, 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 findings of the present 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 remained at a low temperature. In the mass spectrometer according to paragraph 1, the portion of the second ion introduction tube extending from the first ion introduction tube is heated by a heating unit, thereby improving ion measurement sensitivity compared to conventional methods.

[0055] (Section 2) The mass spectrometer according to paragraph 2 is the mass spectrometer according to paragraph 1, The second iontophoretic tube has the first iontophoretic tube and an extension tube connected to the first iontophoretic tube.

[0056] (Section 3) The mass spectrometer according to paragraph 3 is the mass spectrometer according to paragraph 1, The second iontophoretic tube is composed of a single tube.

[0057] The second ion introduction tube in the mass spectrometer of paragraph 1 may be a single ion introduction tube having a length such that the end on the ionization section side is positioned close to the position on the sample surface that is irradiated with laser light, as in the mass spectrometer of paragraph 3, or may have a first ion introduction tube and a second tube detachably connected to the first ion introduction tube, as in the mass spectrometer of paragraph 2. In the mass spectrometer of paragraph 2, the second ion introduction tube can be easily configured by connecting an extension tube while the first ion introduction tube that penetrates the partition remains attached.

[0058] (Section 4) The mass spectrometer according to paragraph 4 is a mass spectrometer according to any one of paragraphs 1 to 3, The heating unit is provided so as to surround the second iontophoresis tube and has a heating element that generates heat when energized.

[0059] In the mass spectrometer of paragraph 4, the ion introduction tube is heated by a heating element that generates heat when energized, thereby heating the second ion introduction tube to a higher temperature and improving the ion measurement sensitivity.

[0060] (Section 5) The mass spectrometer according to paragraph 5 is the mass spectrometer according to paragraph 4, The heating element and the second iontophoresis tube are configured as separate bodies and are detachable from each other.

[0061] In the mass spectrometer according to paragraph 5, if sample components adhere to the inside of the second ion introduction tube or if the second ion introduction tube becomes clogged, only the second ion introduction tube can be removed and cleaned or replaced. Furthermore, if a malfunction such as a break in the heating element occurs, only the heating element can be replaced. This reduces costs compared to replacing both the second ion introduction tube and the heating element. [Explanation of symbols]

[0062] 1...Mass spectrometer 11...Ionization chamber 111...ESI probe 12...Sample plate 13...Sample plate holder 14...Movement mechanism 15...Laser light source 16...Mirror 17...Lens 18...Optical microscope 20...Vacuum chamber 21...First intermediate vacuum chamber 211...Ion lens 212...Skimmer 22...Second intermediate vacuum chamber 221...Ion Guide 23...Third intermediate vacuum chamber 231...Quadrupole mass filter 232...Collision cell 233...Multipole ion guide 234...Ion lens 24…Analysis room 241...Ion lens 242...Orthogonal acceleration section 2421...Extrusion electrode 2422...Pull-in electrode 243...acceleration electrode 244...Flight tube 245...Reflectron electrode 246...Ion detector 3...Sample introduction section 31…1st pipe 32...Pipe attachment part 33...heating element 34...1st power supply 35...Pipe connection part 36…Second pipe 37...heating element 38…Second power supply 41...First pipe mounting member 42...Second pipe mounting member 43...Cartridge heater 5...Control unit 51...Storage section 52...Measurement execution unit 53...Analysis processing unit 6...Input section 7…Display section 80...Bulkhead C...Ion optical axis

Claims

1. A mass spectrometer having an ionization unit selectively equipped with a first ion source that sprays and ionizes a liquid sample in an atmospheric pressure environment, and a second ion source that ionizes the sample by irradiating it with laser light in an atmospheric pressure environment, a mass analysis unit provided in a vacuum chamber connected to the ionization unit via a partition wall, which separates and detects ions generated in the ionization unit according to their mass-to-charge ratios; an ion introduction tube provided through the partition wall and configured to introduce ions generated in the ionization unit into the vacuum chamber; an extension tube that is attached to a tip of the ion introduction tube on the ionization unit side when the second ion source is in use and that is detached from the ion introduction tube when the first ion source is in use; a heating unit that heats the extension tube attached to the tip of the ion introduction tube on the ionization unit side; A mass spectrometer comprising:

2. A mass spectrometer having an ionization unit selectively equipped with a first ion source that sprays and ionizes a liquid sample in an atmospheric pressure environment, and a second ion source that ionizes the sample by irradiating it with laser light in an atmospheric pressure environment, a mass analysis unit provided in a vacuum chamber connected to the ionization unit via a partition wall, which separates and detects ions generated in the ionization unit according to their mass-to-charge ratios; a tube mounting part to which either a first ion introduction tube, which is provided to penetrate the partition and introduces ions generated in the ionization unit into the vacuum chamber, and which is used when the first ion source is in use, or a second ion introduction tube, which is provided to penetrate the partition and introduces ions generated in the ionization unit into the vacuum chamber, and which is used when the second ion source is in use, and which is composed of a single tube having a portion extended from the first ion introduction tube toward the ionization unit so that a tip thereof is located closer to the ionization unit than the first ion introduction tube when in use; a heating unit that heats an extension portion of the second ion introduction tube attached to the tube attachment unit, the extension portion extending from the first ion introduction tube toward the ionization unit; A mass spectrometer comprising:

3. The mass spectrometer according to claim 1 , wherein the heating unit includes a heating element that is provided so as to surround the extension tube and generates heat when energized.

4. 4. The mass spectrometer according to claim 3, wherein the heating element and the extension tube are separate and detachable from each other.

5. The mass spectrometer according to claim 2 , wherein the heating unit is provided so as to surround the extension portion and includes a heating element that generates heat when energized.

6. 6. The mass spectrometer according to claim 5, wherein the heating element and the extension portion are separate and detachable from each other.

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