WO2024100977A1

WO2024100977A1 - Mass spectrometer

Info

Publication number: WO2024100977A1
Application number: PCT/JP2023/032730
Authority: WO
Inventors: 健太寺島; 郷志笠松
Original assignee: 株式会社島津製作所
Priority date: 2022-11-10
Filing date: 2023-09-07
Publication date: 2024-05-16

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

Mass Spectrometer

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.

In order to identify and quantify target substances contained in liquid samples, mass spectrometers equipped with an ionization section that generates ions of the target substance by electrospray ionization (ESI) are used. In ESI, the liquid sample is charged and sprayed into an ionization chamber that is at approximately atmospheric pressure, and the ions are introduced into the mass analysis section in the 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 the ion introduction tube is heated to promote desolvation of the ions and increase the efficiency of ion generation.

In addition, 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 samples using the Matrix-Assisted Laser Desorption/Ionization method.

　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. A mass spectrometer with atmospheric pressure MALDI is equipped with an ionization section that is at atmospheric pressure (atmospheric pressure MALDI) and a mass analysis section that is installed in a vacuum chamber and separates and detects ions according to their mass-to-charge ratio.

In a mass spectrometer equipped with atmospheric pressure MALDI, mass analysis is performed as follows:

First, a pretreatment is performed by applying a matrix substance, which is an easily ionized substance, to the surface of the sample placed on the sample plate, forming microcrystals of the matrix substance that incorporate the molecules of the sample on the surface of the sample. When the sample plate with the pretreated sample placed on it is set in a designated 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.

Ions generated from the sample molecules are taken in through the inlet end (ion intake port) 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 the ion detector. By correlating the signal intensities sequentially output by the ion detector with the mass-to-charge ratios 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.

　ESI and atmospheric pressure MALDI use different ionization methods, but they can use the same mass spectrometer. However, in atmospheric pressure MALDI, mirrors for reflecting the light irradiated onto 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.

JP 2021-196303 A

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, and the efficiency of ion intake into the ion introduction tube becomes poor. For this reason, when ions are generated by atmospheric pressure MALDI, for example, an extension tube is connected to the ion introduction tube used to introduce the ions generated by ESI into the vacuum chamber, and the inlet end of the ion introduction tube is positioned near the measurement point. However, it has been found that when the ion introduction tube used in ESI is lengthened by connecting an extension tube to it and ions generated by atmospheric pressure MALDI are introduced into the vacuum chamber, it may not be possible to measure the ions with sufficient sensitivity.

The problem that this invention aims to solve 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.

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 irradiates a laser beam onto a sample in an atmospheric pressure environment to ionize the sample are alternatively installed as an ionization unit,
a mass spectrometry unit provided in a vacuum chamber connected to the ionization unit via a partition wall, the mass spectrometry unit separating and detecting the 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 a first ion introduction tube that is used when the first ion source is used and that is used when the second ion source is used;
a heating unit configured to heat a portion of the second ion introduction tube that extends from the first ion introduction tube toward the ionization unit.

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

If an ion introduction tube used in ESI or APCI is used as is when atmospheric pressure MALDI or the like is used, the distance from the inlet end of the ion introduction tube to the measurement point becomes long, and the efficiency of ion intake into the ion introduction tube becomes poor. Therefore, in the present invention, when the second ion source is used, a second ion introduction tube that is longer than the first ion introduction tube used when the first ion source is used is used. According to the knowledge 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 that extended from the first ion introduction tube to the ionization section side was not heated and became low temperature. In the mass spectrometer according to the present invention, the part of the second ion introduction tube that extended from the first ion introduction tube to the ionization section side is heated by the heating section, and the ion measurement sensitivity can be improved compared to the past.

1 is a diagram showing the configuration of a main part of an embodiment of a mass spectrometer according to the present invention; FIG. 2 is a schematic diagram of a sample introduction section of the mass spectrometer of the present embodiment (when using ESI). FIG. 2 is a schematic diagram of a sample introduction section of the mass spectrometer of the present embodiment (when atmospheric pressure MALDI is used). 1 shows an example of the configuration of a sample introduction section of a mass spectrometer according to the present embodiment (when atmospheric pressure MALDI is used). FIG. 2 is a diagram showing a removable portion of the sample introduction section of the mass spectrometer of the present embodiment (when atmospheric pressure MALDI is used). 4 shows the results of measuring the temperature of the second iontophoretic tube in the comparative example and the example. The results of measuring the ionic intensity of AngII and chloroquine in the comparative example and the example. 13 shows the results of measuring the intensity of ions derived from mouse brain under different heating temperatures of the tip in the example.

One embodiment of a mass spectrometer according to the present invention will be described below with reference to the drawings.

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

Atmospheric pressure MALDI is equipped with 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 (position shown by a dashed line in FIG. 1) and a measurement position (position shown by a solid line in FIG. 1). It also has an optical system including a laser light source 15, a mirror 16 that reflects the light emitted from the laser light source 15 and irradiates it onto 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 is also equipped with an optical microscope 18 for observing the surface of the sample on the sample plate 12.

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

Inside the vacuum chamber 20, in order from the ionization chamber 11 side, there are a first intermediate vacuum chamber 21, a second intermediate vacuum chamber 22, a third intermediate vacuum chamber 23, and an analysis chamber 24. 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 toward the analysis chamber 24.

In the first intermediate vacuum chamber 21, an ion lens 211 consisting of multiple ring electrodes is arranged to focus the ions generated in the ionization chamber 11 and introduced through the sample introduction section 3 near the ion optical axis C, which is the central axis of the ion flight direction, while transporting them to the subsequent stage.

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

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, a quadrupole mass filter 231 consisting of four rod electrodes, a collision cell 232, and an ion lens 234 consisting of multiple ring electrodes are arranged. Inside the collision cell 232, a multipole ion guide 233 consisting of multiple rod electrodes is arranged. Inside the collision cell 232, a CID gas such as argon or nitrogen is continuously or intermittently supplied at an appropriate timing.

The third intermediate vacuum chamber 23 and the analysis chamber 24 are connected by a small diameter hole provided in the partition between them. In the analysis chamber 24, an ion lens 241 consisting of multiple ring electrodes, an orthogonal acceleration section 242, an acceleration electrode 243, a flight tube 244, a reflectron electrode 245, and an ion detector 246 are arranged. The orthogonal acceleration section 242 is composed of an extrusion electrode 2421 and a retraction electrode 2422, each of which is a plate-shaped electrode, and is arranged opposite each other across the flight path of the ions transported by the ion lens 241. The retraction electrode 2422 has an opening for passing the ions. The acceleration electrode 243 is composed of multiple ring electrodes for accelerating the ions whose flight direction has been changed by the orthogonal acceleration section 242. The flight tube 244 is a cylindrical electrode, and the flight space of the ions is defined inside it. The reflectron electrode 245 is composed of multiple ring electrodes, and a predetermined voltage is applied to each electrode so as to form a potential gradient in which the potential increases toward the rear stage. Ions accelerated by the acceleration 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 turned around ions by the potential gradient formed by the reflectron electrode 245.

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

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 the measurement conditions set by the user. The analysis processing unit 53 performs processing such as generating a mass spectrum from the measurement data. The actual 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.

The mass analysis performed by the mass spectrometer 1 of this embodiment is the same as in the conventional method, so it will be explained briefly below.

First, a pretreatment is performed by applying a matrix substance, which is a substance that is easily ionized, to the surface of the sample placed on the sample plate 12, thereby forming microcrystals of the matrix substance that incorporate the molecules of the sample on the surface of the sample. Next, the sample plate 12 on which the pretreated sample is placed is placed on the sample plate holder 13, and the sample plate holder 13 is placed at the measurement position. Then, when laser light is irradiated from the laser light source 15, the microcrystals of the matrix substance are heated, and the sample molecules are desorbed and ionized. Ions generated from the sample molecules in the ionization chamber 11 enter the vacuum chamber 20 through the sample introduction section 3. The ions that enter the vacuum chamber 20 are transported by the ion lens 211 and the ion guide 221, and then enter the quadrupole mass filter 231. In the quadrupole mass filter 231, ions having 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 the

ion lenses

234 and 241 and enter the orthogonal acceleration section 242. The product ions, whose flight direction is changed to a substantially orthogonal direction in the orthogonal acceleration section 242, are accelerated by the acceleration electrode 243, enter a flight space surrounded by a flight tube 244, and fly back and forth due to the potential gradient formed by the reflectron electrode 245 located at the end of the flight tube, before being detected by the ion detector 246.

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 flight time of each ion into a mass-to-charge ratio based on the flight time-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 on two axes.

The mass spectrometer 1 of this embodiment is characterized by the configuration of the sample introduction section 3 provided in the partition 80 between the ionization chamber 11 and the first intermediate vacuum chamber 21. The sample introduction section 3 will be described below.

FIG. 2 is a schematic diagram showing the configuration of the sample introduction section 3 when mass spectrometry is performed on ions generated by ESI. The sample introduction section 3 has a first tube 31 (corresponding to the first ion introduction tube in the present invention), a tube attachment section 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 to supply 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 by the pressure difference between the ionization chamber 11 and the vacuum chamber 20.

FIG. 3 is a schematic diagram showing the configuration of the sample introduction section 3 when performing mass analysis on ions generated by atmospheric pressure MALDI. The sample introduction section 3 has a first tube 31 attached to a tube attachment section 32, a tube connection section 35, and a second tube 36 connected to the first tube 31 by the tube connection section 35. The second tube 36 is also made of, for example, stainless steel. The second tube 36 and the tube connection section 35 are detachable from the first tube 31. By connecting the second tube 36 to the first tube 31 in this way, 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 the present invention, and the second tube 36 corresponds to the portion of the second ion introduction tube that extends from the first ion introduction tube to the ionization section side in the present invention. In this way, by using a longer ion introduction tube than when ESI is used, the inlet end of the ion introduction tube can be brought closer to the sample surface, and more ions emitted from the sample can be introduced from the ion introduction tube (second tube 36 and first tube 31) to the mass analysis section. Here, the ion introduction tube for atmospheric pressure MALDI is constructed by connecting the first tube 31 and the second tube 36 with the tube connection part 35, but a single long ion introduction tube may also be used.

A heating element 33, shown diagrammatically as 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 source 34. Although a heater wire is shown diagrammatically in FIGS. 2 and 3, various items capable of heating the first tube 31 can be used, and for example, a cartridge heater (such as a block heater), a microsheath heater, a ceramic coating, etc. can be used as the heating element 33. Alternatively, the first tube 31 may be heated by irradiation with infrared light, etc.

Similarly, a heating element (corresponding to the heating section in this invention) 37, shown diagrammatically 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 this invention. Various methods can be used to heat the second tube 36; for example, the second tube 36 can be heated by 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.

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

In conventional mass spectrometers, when performing mass analysis on ions generated by atmospheric pressure MALDI, the ion introduction tube was simply extended by connecting a second tube to the first tube, but in that case, it was sometimes not possible to measure ions with sufficient sensitivity. There are various possible reasons for this, but it is thought that because only the first tube is heated and the second tube is not heated and is at a low temperature, for example, the molecules of the matrix material applied during sample pretreatment do not detach from the ions of the sample molecules, or ions derived from the sample lose energy through collisions with low-temperature gas molecules and attach to the ion introduction tube, resulting in their disappearance.

In contrast, in the mass spectrometer 1 of this 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 with reference to the measurement results, by heating the second tube 36, ions can be detected with higher sensitivity than before.

Next, the results of measurements that confirmed that the ion detection sensitivity is improved by heating the second tube 36 in the mass spectrometer 1 of this embodiment will be described. Here, as shown in FIG. 4, the first tube mounting member 41 is arranged on the outer periphery of the first tube 31, and the second tube mounting member 42 is arranged on 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 stainless steel having electrical conductivity. The first tube mounting member 41 and the second tube mounting member 42 are detachable. The first tube mounting member 41 is connected to the first power source 34. When electricity is applied from the first power source 34 to the first tube mounting member 41 and the first tube 31, the first tube 31, which has a large electrical resistance, generates heat. Inside the second tube mounting member 42, a cartridge heater 43 is arranged along the outer periphery of the second tube 36. When a voltage is applied from the second power source 38 to the cartridge heater 43, the cartridge heater 43 generates heat and the second tube 36 is heated.

In the sample introduction section 3 of the configuration example of FIG. 4, the parts shown in FIG. 5 (tube connection section 35, second tube 36, second tube attachment member 42, and cartridge heater 43) can be attached and detached. Therefore, when exchanging between ESI and atmospheric pressure MALDI, it is only necessary to attach and detach the parts shown in FIG. 5, and there is no need to remove the first tube 31 attached to the bulkhead 80 by the tube attachment section 32.

In addition, in the configuration example shown in FIG. 4, the second tube 36 and the cartridge heater 43 (including the second tube attachment 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 broken wire, only the cartridge heater 43 can be replaced. This allows for reduced costs compared to replacing the integrated second tube 36 and cartridge heater 43 (including the second tube attachment member 42).

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.

As the measurement results are shown in Figure 6, in the embodiment (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).

In addition, the ions generated from AngII (angiotensin II) and chloroquine were measured for each of the comparative example and 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.

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

As shown in Figure 8, the maximum heating temperature of the tip in this measurement (heating temperature of second tube 36) was approximately 430°C, and at least up to this temperature, the higher the heating temperature, the higher the measured ion intensity. Although it is necessary to take into account the heat resistance of the sample, it is thought that the higher the second tube 36 is heated to, at least up to over 400°C, the better the ion measurement sensitivity will be. Note that, although this depends on the material of second tube 36, taking into account heat resistance, etc., it is appropriate to set the upper limit of the heating temperature of second tube 36 to around 500°C.

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.

In the above embodiments and examples, atmospheric pressure MALDI and ESI were used as the ion source, 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.

In the above embodiment 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, but 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.

In the above embodiment, a configuration for heating the first tube 31 and the second tube 36 has been described, but it is also effective to provide a means for suppressing heat dissipation in addition to the heating section. Specifically, a heat insulating material may be wrapped around the outer circumference 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 disposed so as to surround the first tube 31 and/or the second tube 36.

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

(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 irradiates and ionizes the sample with laser light in an atmospheric pressure environment are alternatively installed as an ionization unit,
a mass spectrometry unit provided in a vacuum chamber connected to the ionization unit via a partition wall, the mass spectrometry unit separating and detecting the 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 a first ion introduction tube that is used when the first ion source is used and that is used when the second ion source is used;
a heating unit configured to heat a portion of the second ion introduction tube that extends from the first ion introduction tube toward the ionization unit.

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 in an atmospheric pressure environment, and a second ion source that irradiates a sample to which a matrix substance has been mixed or applied with laser light in an atmospheric pressure environment to ionize the sample. The first ion source that sprays and ionizes a liquid sample is, for example, a DUIS equipped with ESI, APCI, or both. The second ion source that ionizes a sample to which a matrix substance has been mixed or applied with laser light in an atmospheric pressure environment is atmospheric pressure MALDI.

If an ion introduction tube used in ESI or APCI is used as is in atmospheric pressure MALDI, the distance from the inlet end of the ion introduction tube to the measurement point becomes long, and the efficiency of ion introduction into the ion introduction tube becomes poor. Therefore, in the mass spectrometer according to paragraph 1, when the second ion source is used, a second ion introduction tube that is longer than the first ion introduction tube used when the first ion source is used is used. According to the knowledge obtained by the present inventor, in the past, when using the second ion introduction tube, it was not possible to measure ions with sufficient sensitivity because the part of the second ion introduction tube that extended from the first ion introduction tube was not heated and became low temperature. In the mass spectrometer according to paragraph 1, the part of the second ion introduction tube that extended from the first ion introduction tube is heated by a heating unit, thereby improving the ion measurement sensitivity compared to the past.

(Section 2)
A mass spectrometer according to paragraph 2 is a 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.

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

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 located close to the position where the laser light is irradiated on the sample surface, 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 bulkhead is still attached.

(Section 4)
A mass spectrometer according to paragraph 4 is a mass spectrometer according to any one of paragraphs 1 to 3,
The heating section is provided so as to surround the second iontophoretic tube and has a heating element that generates heat when electricity is applied thereto.

In the mass spectrometer of paragraph 4, the ion introduction tube is heated by a heating element that generates heat when electricity is passed through it, thereby heating the second ion introduction tube to a higher temperature and improving the measurement sensitivity of ions.

(Section 5)
A mass spectrometer according to claim 5, in the mass spectrometer according to claim 4,
The heating element and the second iontophoretic tube are configured as separate bodies and are detachable from each other.

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. Also, if a malfunction occurs such as a broken wire in the heating element, only the heating element can be replaced. This allows for reduced costs compared to replacing both the second ion introduction tube and the heating element.

1... Mass spectrometer 11... Ionization chamber 111... ESI probe 12... Sample plate 13... Sample plate holder 14... Moving 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 chamber 241... Ion 3. Reflectron lens 242...orthogonal acceleration section 2421...push electrode 2422...pull-in electrode 243...acceleration electrode 244...flight tube 245...reflectron electrode 246...ion detector 3...sample introduction section 31...first tube 32...tube attachment section 33...heating element 34...first power supply 35...tube connection section 36...second tube 37...heating element 38...second power supply 41...first tube attachment member 42...second tube attachment member 43...cartridge heater 5...control section 51...memory section 52...measurement execution section 53...analysis processing section 6...input section 7...display section 80...partition wall C...ion optical axis

Claims

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 a laser beam in an atmospheric pressure environment are alternatively installed as an ionization unit,
a mass spectrometry unit provided in a vacuum chamber connected to the ionization unit via a partition wall, the mass spectrometry unit separating and detecting the 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 a first ion introduction tube that is used when the first ion source is used and that is used when the second ion source is used;
a heating unit configured to heat a portion of the second ion introduction tube that extends from the first ion introduction tube toward the ionization unit.
The mass spectrometer according to claim 1, wherein the second ion introduction tube has the first ion introduction tube and an extension tube connected to the first ion introduction tube.
The mass spectrometer of claim 1, wherein the second ion introduction tube is composed of a single tube.
The mass spectrometer according to claim 1, wherein the heating unit is provided so as to surround the second ion introduction tube and has a heating element that generates heat when electricity is applied.
The mass spectrometer according to claim 4, wherein the heating element and the second ion introduction tube are separate and detachable from each other.