Ion analyzer

Abstract

An ion analyzer (1) is provided with: a reaction chamber (132) into which precursor ions derived from a sample component are introduced, at least a part of the inner peripheral surface of the reaction chamber (132) being formed from an insulating material (1323); and an active particle introduction unit (4) that generates active particles from the raw material gas and introduces the active particles into the reaction chamber. One embodiment of the present invention is also provided with: a multi-pole ion guide (1333) comprising a plurality of electrodes (1331) arranged around an ion optical axis (C), which is the central axis of the flight path of ions in the reaction chamber, the plurality of electrodes being formed by cutting out a portion (1334), which is a plate-shaped or columnar base material, other than the portion facing the ion optical axis; and the surface area is reduced compared with that of the base material.

Description

Technical Field

[0001] This invention relates to an ion analysis device that reacts precursor ions derived from sample components with active particles such as free radicals to generate product ions for measurement. Background Technology

[0002] To identify components in a sample or to estimate their molecular structure, mass spectrometry (MS / MS) analysis is performed. In MS / MS analysis, ions derived from the sample components (precursor ions) are introduced into a reaction chamber, where they dissociate to generate product ions, which are then separated and detected by mass. Sample components or estimated molecular structures can be identified based on partial structural information obtained from the mass-to-charge ratio of the detected product ions.

[0003] One method for dissociating precursor ions is to react them with various types of free radicals, such as hydrogen radicals, oxygen radicals, hydroxyl radicals, and nitrogen radicals (e.g., Patent Documents 1-4). For example, by reacting precursor ions derived from peptides with free radicals to dissociate them, product ions reflecting the structure of the peptide, such as its amino acid sequence, are generated. By analyzing the mass spectra of these product ions, the structure of the peptide can be deduced.

[0004] Non-patent documents 1 and 2 describe radical generation devices used in performing the above-described dissociation method. These radical generation devices include a tube made of dielectric material and a helical antenna wound around the outer periphery of the tube. High-frequency power is supplied to the helical antenna while a raw material gas (e.g., water vapor) flows through the inside of the tube to generate plasma from the raw material gas, thereby generating radicals. Patent document 4 describes a mass spectrometry device that connects one end of the aforementioned tube to a reaction chamber and supplies radicals to the reaction chamber.

[0005] Existing technical documents Patent documents Patent Document 1: Japanese Patent Application Publication No. 2019-191081 Patent Document 2: International Publication No. 2019 / 155725 Patent Document 3: International Publication No. 2021 / 095105 Patent Document 4: International Publication No. 2022 / 059247 Patent Document 5: Japanese Patent Application Publication No. 2007-128694 Non-patent literature Non-patent literature 1: Yuji Simabukuro et al., “Tandem mass spectrometry analysis of peptide ions using microwave-excited hydrogen and water plasma”, Analytical Chemistry, 2018, Vol. 90, No. 12, pp. 7239-7245. Non-Patent Document 2: Yuji Simabukuro, “Comprehensive Study on Low-Energy Atomic Hydrogen Beams: From Generation to Velocity Distribution Measurement” (Doctoral Dissertation Text), [Online], [Searched June 15, 2023], Doshisha University Academic Institutions Database, Internet <URL: https: / / doshisha.repo.nii.ac.jp / ?action=pages_view_main&active_action=repository_view_main_item_detail&item_id=1608&item_no=1&page_id=13&block_id=100> Non-patent literature 3: Harmeet Singh et al., “Recombination coefficients of O and N radicals in stainless steel”, Journal of Applied Physics, 2000, Vol. 88, No. 6, pp. 3748-3755. Non-Patent Literature 4: JC Greaves et al., “Atom recombination on surfaces, Part 5—Oxygen atoms on oxide surfaces,” *Trans. Faraday Soc.*, 1959, Vol. 55, pp. 1346-1354. Non-Patent Literature 5: Rok Zaplotnik et al., “Atomic oxygen and hydrogen loss coefficients on functionalized polyethylene terephthalate, polystyrene and polytetrafluoroethylene polymers”, May 2018, Plasma Processes and Polymers, 15(9):e1800021, DOI:10.1002 / ppap.201800021, [online], [retrieved June 29, 2023], <URL: https: / / onlinelibrary.wiley.com / doi / abs / 10.1002 / ppap.201800021> Non-Patent Document 6: “Thermal Spraying”, Process Co., Ltd., [Online], [Searched August 10, 2023], <URL: http: / / www.process-1.co.jp / product / index-use04.php> Non-Patent Document 7: "Types and Characteristics of Teflon Coatings", Yumoto Electric Co., Ltd., [Online], [Searched August 10, 2023], <URL: https: / / www.yumoto.jp / technology / onepoint / teflon-coating> Non-Patent Document 8: “Key Points! Substrate Design Suitable for Teflon™ Fluoropolymer Coatings,” Coating Magazine, Yoshida SKT Co., Ltd., [Online], [Searched August 10, 2023], <URL: https: / / www.y-skt.co.jp / magazine / coating / base_engineering / > Non-Patent Document 9: "PBI / PI Coating High-Performance Plastic Coating", Yoshida SKT Co., Ltd., [Online], [Searched August 10, 2023], <URL: https: / / www.y-skt.co.jp / products-pbi-pi.html> Non-Patent Literature 10: Hidenori Takahashi et al. 7, “Hydrogen Adsorption / Extraction Dissociation (HAD) of Gas-Phase Peptide Ions for Tandem Mass Spectrometry Analysis”, Analytical Chemistry, 2016, Vol. 88, No. 7, pp. 3810-3816 Summary of the Invention The technical problem that the invention aims to solve In existing mass spectrometry devices, the reaction chamber is located inside a cylindrical body made of metal. For example, as described in Non-Patent Document 3, free radicals have a high recombination coefficient with metals. When free radicals introduced into the reaction chamber come into contact with the inner circumferential surface of the reaction chamber, they easily recombine with the metal atoms constituting that inner circumferential surface and disappear. Therefore, there is a problem that it is difficult to increase the density of free radicals within the reaction chamber.

[0006] This example illustrates the dissociation of precursor ions by reacting them with free radicals, but the same problem exists when other reactive particles, such as ozone or metastable particles, are used to dissociate precursor ions.

[0007] The technical problem to be solved by the present invention is to suppress the disappearance of active particles introduced into the reaction chamber in an ion analysis device in which precursor ions and active particles such as free radicals derived from sample components are introduced into the reaction chamber to react and generate product ions for measurement.

[0008] Solution to the above technical problems The ion analysis apparatus of the present invention, completed to solve the above-mentioned technical problems, includes: A reaction chamber, at least a portion of which is formed of an insulating material on its inner circumferential surface, through which precursor ions derived from the sample components are introduced; and The active particle introduction section generates active particles from the raw material gas and introduces the active particles into the reaction chamber.

[0009] Invention Effects In existing mass spectrometry devices, most of the active particles introduced into the reaction chamber recombine with the metal atoms constituting the inner peripheral surface of the reaction chamber and disappear. In contrast, in the ion analysis device of the present invention, at least a portion of the inner peripheral surface of the reaction chamber is composed of an insulating material. The recombination coefficient between the active particles and the insulating material is lower than that between the active particles and the metal, meaning that even if the active particles introduced into the reaction chamber come into contact with molecules of the insulating material constituting the inner peripheral surface of the reaction chamber, their probability of disappearance is low. Therefore, compared to existing mass spectrometry devices, the disappearance of active particles introduced into the reaction chamber can be suppressed. Attached Figure Description

[0010]

【 Figure 1 [Image 1] is a schematic structural diagram of an embodiment of the ion analysis device of the present invention, namely a mass spectrometry device.

[0011]

Figure 2

[0012] 【 Figure 3 The diagram shows the structure of the electrodes that constitute the multipolar ion guide in an existing mass spectrometry device.

[0013] 【 Figure 4 [Illustration 1] is a diagram showing the structure of the electrodes constituting the multipolar ion guide in the mass spectrometry apparatus of this embodiment.

[0014] 【 Figure 5 [Image caption: Photograph of the electrodes constituting the multipolar ion guide in the mass spectrometry apparatus of this embodiment.]

[0015] 【 Figure 6 The figure shown is a diagram illustrating how the electrode of this embodiment is mounted on the electrode holder.

[0016] 【 Figure 7 [Image 1] is a diagram showing the collision chamber of this embodiment as viewed along the ion optical axis.

[0017] 【 Figure 8 The graph shows the results of measurements taken to compare the reaction efficiency of existing mass spectrometry devices with that of the mass spectrometry device of this embodiment.

[0018] 【 Figure 9 [Illustration 1] is a diagram showing the structure of the electrodes constituting a multipolar ion guide in other embodiments. Detailed Implementation

[0019] Hereinafter, embodiments of the mass spectrometry apparatus of the present invention will be described with reference to the accompanying drawings. Furthermore, in the drawings used in the following description, the scaling ratios of each component have been appropriately altered from the actual scale for easier understanding of the structure of the main components in this embodiment, and some component illustrations have been omitted.

[0020] <Simplified Structure of Mass Spectrometry Device 1> Figure 1 This diagram illustrates a schematic structure of one embodiment of the present invention, namely, the mass spectrometry apparatus 1. The mass spectrometry apparatus 1 of this embodiment is a quadrupole-time-of-flight (Q-TOF) mass spectrometry apparatus equipped with an atmospheric pressure ion source. This mass spectrometry apparatus 1 can be pre-connected to a liquid chromatograph (LC) and used as a liquid chromatography-mass spectrometry apparatus.

[0021] The mass spectrometer apparatus 1 of this embodiment includes an ionization chamber 10 and a vacuum chamber 100. The ionization chamber 10 is filled with an atmosphere at approximately atmospheric pressure. The vacuum chamber 100 is internally divided into multiple chambers (four chambers in this embodiment), which are sequentially arranged from the side closest to the ionization chamber 10 as a first intermediate vacuum chamber 11, a second intermediate vacuum chamber 12, a first analysis chamber 13, and a second analysis chamber 14. Each of these chambers is evacuated by a vacuum pump (rotary pump and / or turbomolecular pump, not shown), and the apparatus has a structure of a multi-stage differential evacuation system with the vacuum level increasing sequentially from the approximately atmospheric pressure atmosphere of the ionization chamber 10 towards the high vacuum atmosphere of the second analysis chamber 14.

[0022] An electrospray ionization (ESI) probe 101 is provided in the ionization chamber 10 to charge and spray a liquid sample. A liquid sample, for example containing sample components separated by a chromatographic column of an LC (not shown), is introduced into the ESI probe 101.

[0023] The ionization chamber 10 is connected to the first intermediate vacuum chamber 11 via a narrow desolvation tube 102 heated by a heat source (not shown). The first intermediate vacuum chamber 11 is equipped with an ion guide 111, which consists of a plurality of rod-shaped electrodes arranged around an ion optical axis C, which serves as the central axis of the ion flight path, and focuses the ions in the vicinity of the ion optical axis C.

[0024] The first intermediate vacuum chamber 11 and the second intermediate vacuum chamber 12 are separated by a tapered plate 112 with a small hole at the top. An ion guide 121 is also disposed in the second intermediate vacuum chamber 12, which consists of a plurality of rod-shaped electrodes arranged around the ion optical axis C, to focus ions in the vicinity of the ion optical axis C.

[0025] In the first analysis chamber 13, arranged along the ion optical axis C are: a quadrupole mass filter 131 that separates ions according to their mass-to-charge ratio (m / z), a collision chamber 132 containing a multipolar ion guide 133, and an ion transport electrode 134 for transporting ions passing through the collision chamber 132 to subsequent stages. The quadrupole mass filter 131 and the multipolar ion guide 133 are each composed of multiple rod-shaped electrodes. The ion transport electrode 134 is composed of multiple annular electrodes. The detailed internal structure of the collision chamber 132 containing the multipolar ion guide 133 will be described later.

[0026] An opening 1321 for inserting a discharge tube 410 into the free radical generation unit 4 is provided on the wall of the collision chamber 132. The structure of the free radical generation unit 4 will be described later. Furthermore, a cylindrical tube connection component 1322 is provided, one end of which surrounds the opening 1321. The collision chamber 132 is also connected to a collision-induced dissociation (CID) gas supply source 61. A valve 62 is provided in the flow path connecting the CID gas supply source 61 and the collision chamber 132 to regulate the flow rate of CID gas (e.g., an inert gas such as argon) supplied from the CID gas supply source 61 to the collision chamber 132.

[0027] In the collision chamber 132, the following methods can be performed: a dissociation method in which precursor ions are dissociated by free radicals such as oxygen free radicals supplied from the free radical generation unit 4, and a collision-induced dissociation (CID) method in which precursor ions are given energy to accelerate them and enter the collision chamber 132, and are dissociated by colliding with CID gas.

[0028] The second analysis chamber 14 includes: an ion transport electrode 141 for transporting ions incident from the first analysis chamber 13; an orthogonal acceleration unit 142 having a set of ejection and introduction electrodes arranged opposite each other across the ion optical axis C; an acceleration electrode 143 for accelerating ions sent out by the orthogonal acceleration unit 142 to the flight space; a reflection electrode 144 for forming a refracting trajectory of ions in the flight space; an ion detector 145; and a flight tube 146 forming the flight space inside. The ion detector 145 is, for example, an electron multiplier tube or a microchannel plate.

[0029] The mass spectrometer apparatus 1 of this embodiment also includes a control / processing unit 7, an input unit 81, and a display unit 82. The control / processing unit 7 includes a storage unit 71. The storage unit 71 stores information such as analytical conditions (measurement conditions, analytical methods, etc.) for various compounds. The control / processing unit 7 includes an analytical execution unit 72 as a functional block. The analytical execution unit 72 sets analytical conditions according to instructions from the user and performs sample measurement and analysis of measurement data based on the set analytical conditions. The control / processing unit 7 is, for example, composed of a general-purpose personal computer (PC), and various functions are realized by executing dedicated control / processing software installed on the computer through a processor.

[0030] <Simplified structure of free radical generation section 4> Figure 2This is a schematic cross-sectional view of the main part of the structure of the plasma generation unit 41 in the free radical generation unit 4. The plasma generation unit 41 generates plasma from the raw material gas supplied from the raw material gas supply source 48 and introduces the free radicals generated in the plasma into the collision chamber 132. Examples of raw material gases used include water vapor, oxygen, nitrogen, dry air, and hydrogen. A microwave power supply 46 supplies power to the helical antenna 411 (described later) for plasma generation. The amount of raw material gas supplied from the raw material gas supply source 48 is regulated by a valve 40 provided in the flow path connecting the raw material gas supply source 48 and the discharge tube 410.

[0031] The plasma generation unit 41 includes: a discharge tube 410 made of quartz or alumina, which is both an insulator and a dielectric; a spiral conductor, i.e., a spiral antenna 411, wound around the discharge tube 410 in a spiral shape; an outer conductor portion 412, which is coaxial with the discharge tube 410 and has a cylindrical opening with an inner diameter larger than the outer diameter of the discharge tube 410; a permanent magnet 413 embedded in the outer conductor portion 412; a housing 414 holding the outer conductor portion 412; and a permanent magnet 415 disposed at the bottom of the housing 414. The spiral antenna 411 is made of a metal such as copper, and preferably a material close to pure copper (oxygen-free copper, ductile copper, etc.) with high conductivity and formability. Furthermore, gold plating is preferably applied to its surface to prevent oxidation.

[0032] A microwave supply connector 416 is provided on the housing 414. Furthermore, a light source 417 that emits ultraviolet light into the interior of the discharge tube 410, and a photodetector 418 that detects the plasma generated inside the discharge tube 410 are mounted on the housing 414. The light source 417 is turned on / off based on a control signal sent from the analysis execution unit 72. In this embodiment, a light source 417 emitting deep ultraviolet light with a wavelength of 275 nm or less is used. When light in this wavelength band is irradiated onto the discharge tube 410, which is made of quartz or alumina, electrons are emitted from the wall of the discharge tube 410. This electrons induce plasma. The light source 417 can be, for example, a UV-LED. The photodetector 418 is a detector that is not sensitive to the wavelength band of light emitted from the light source 417, but is sensitive only to the wavelength band of light emitted from the plasma inside the discharge tube 410. The photodetector 418 can be, for example, a photodiode. The detection signal from the photodetector 418 is sent to the control / processing unit 7 and stored in the storage unit 71. The analysis execution unit 72 determines whether plasma is generated by comparing the magnitude of the detection signal from the photodetector 418 with a predetermined threshold.

[0033] The discharge tube 410 is a raw material inlet tube that introduces raw material gas from the raw material gas supply source 48. Inside it, the area where the spiral antenna 411 is wound and irradiated by ultraviolet light from the light source 417 becomes the free radical generation chamber 4101, and its downstream side becomes the free radical transport section 4102.

[0034] The microwave supply connector 416 is a coaxial connector that connects to the microwave power supply 46 via a coaxial cable. The conductive wires of the coaxial connector are connected to one end of the helical antenna 411. Furthermore, the outer conductor portion 412 is grounded. A portion of the helical antenna 411 is electrically connected to the outer conductor portion 412 via a resonator adjustment mechanism 420, at which point the helical antenna 411 is grounded. The helical antenna 411, the outer conductor portion 412, and the resonator adjustment mechanism 420 constitute an electron cyclotron resonance (ECR) resonator. The resonator adjustment mechanism 420 is used for adjusting the ECR resonator. The structure of the resonator adjustment mechanism 420 is the same as described in Patent Document 3, therefore a detailed description is omitted. The microwave power supply 46 supplies power to the resonator via the coaxial cable and the microwave supply connector 416.

[0035] In the plasma generation unit 41 of this embodiment, plasma is generated and maintained using localized inductively coupled discharge and electron cyclotron resonance. In this plasma generation unit 41, the plasma density can be increased and stabilized through ECR.

[0036] A generally disc-shaped magnet holder 51 is mounted on the bottom surface of the housing 414. The housing 414 and the magnet holder 51 serve as a holding member 50 for holding the discharge tube 410. An opening is formed in the center of the magnet holder 51 for the discharge tube 410 and the guide member 52 to pass through. The guide member 52 is a cylindrical member coaxially disposed with respect to the outer periphery of the discharge tube 410, and a compression spring 56 that extends and retracts axially in the discharge tube 410 is mounted on its outer periphery. In addition, a cylindrical protector 53 is provided at the tip of the guide member 52. In the discharge tube 410, the guide member 52 and the protector 53 are disposed on the outer periphery of the tip portion exposed from the magnet holder 51, and the tip of the protector 53 is located further outward than the tip of the discharge tube 410. Thus, the guide member 52, the protector 53, and the compression spring 56 serve as a tube protection member 54 to protect the outer periphery and tip of the portion of the discharge tube 410 exposed from the holding member 50.

[0037] <Installation of the 4-way collision chamber 132 for free radical generation> The collision chamber 132 is fixed to the vacuum chamber 100 via a portion not shown. Openings are formed on the walls of both the vacuum chamber 100 and the collision chamber 132, and a tube connection member 1322 is inserted into two of these openings. The tube connection member 1322 is a cylindrical component with a bottom surface having a through hole, and its bottom is mounted on the opening 1321 of the collision chamber 132. The diameter of the through hole formed on the bottom surface of the tube connection member 1322 is larger than the outer diameter of the discharge tube 410 and smaller than the outer diameter of the protector 53.

[0038] The operation of installing the free radical generation unit 4 onto the collision chamber 132 is the same as in the prior application, so detailed description is omitted. However, in the free radical generation unit 4, the outer side of the discharge tube 410 is protected by the protector 53 until the tip of the discharge tube 410 enters the interior of the collision chamber 132, which can prevent the discharge tube 410 from being damaged when installing the free radical generation unit 4.

[0039] <Brief Structure of Collision Chamber 132> Reference Figures 3-7 This describes the structure of the electrode 1331, which is disposed in the collision chamber 132 and constitutes the multipolar ion guide 133. Figure 3 This is a side view of electrode 2331 (hereinafter also referred to as "existing electrode"), which constitutes the multipolar ion guide in an existing mass spectrometry device. Figure 4 This is a side view of the electrode 1331 (hereinafter also referred to as "the electrode of this embodiment") constituting the multipolar ion guide 133 of the mass spectrometry device 1 of this embodiment. Figure 5 This is a photograph of the electrode of this embodiment used in an actual mass spectrometry apparatus. Figure 5 It's a photo of four electrodes, but in an actual device, such as... Figure 7 As shown, eight electrodes are arranged around the ion optical axis C to form a multipolar ion guide 133. Figure 6 As shown, each electrode is mounted on the electrode holder 1335. Eight electrodes are used in this embodiment, but multiple electrodes 1331, such as four, six, or more than ten, can also be used to construct the ion guide 133.

[0040] The existing electrode 2331 is formed by forming cutouts 2332 at both ends of a rectangular metal plate (e.g., a stainless steel plate), and has a structure similar to that described in Patent Document 5. The cutouts 2332 are the parts into which the electrode holder is inserted, and are installed inside the collision chamber with the central portion 2333 completely exposed.

[0041] In this embodiment, electrode 1331 is formed by forming cutouts 1332 at both ends of a rectangular metal plate (e.g., a stainless steel plate), and by removing a portion of the central portion 1333 exposed within the collision chamber 132 (excluding the portion 1334 facing the ion optical axis C). In this embodiment, by removing the portion of the substrate, which is a generally rectangular metal plate, excluding the portion facing the ion optical axis C, its surface area is reduced compared to that substrate.

[0042] The electrode holder 1335 is made of an insulating material (such as resin or ceramic). The electrode holder 1335 is identical to that described in Patent Document 5, having a centrally opened disc shape with eight holes 1336 formed on one surface. Eight electrodes 1331 are positioned by inserting the cutouts 1332 into these holes 1336. The electrode holder 1335 is fixed to the impact chamber 132 by a mounting portion (not shown).

[0043] like Figure 7 As shown, an insulating sheet 1323 is mounted on the inner circumferential surface of the collision chamber 132. Thus, the surface of the metal (e.g., aluminum) constituting the collision chamber 132 is covered with an insulating material.

[0044] Non-Patent Document 3 states that oxygen recombines (disappears) on the surface of stainless steel with a recombination coefficient γ = 0.17. Non-Patent Document 4 states that oxygen atoms hardly disappear on the surface of oxides. From Non-Patent Document 4, it can be seen that hydrogen radicals disappear more easily than oxygen radicals on the surface of oxides. Non-Patent Document 5 states that, regarding PTFE, the recombination coefficient γ for both hydrogen and oxygen radicals is approximately 0.001.

[0045] As can be seen from Non-Patent Documents 3-5, free radicals tend to disappear easily upon contact with metal. Therefore, reducing the chance of free radicals contacting metal is effective in suppressing their disappearance. Thus, in the mass spectrometry apparatus 1 of this embodiment, an insulating material (insulating sheet 1323) is installed on the inner circumferential surface of the collision chamber 132, making the exposed area of ​​the metal smaller than before. Examples of such insulating materials include, for instance, various resin materials such as polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyoxymethylene (POM), polyimide (PI), and polybenzimidazole (PBI). Furthermore, in this embodiment, a polyimide sheet is used as the insulating sheet 1323.

[0046] Furthermore, in this embodiment, by removing a portion of the central portion 1333 of the electrode 1331, the surface area of ​​the electrode 1331 is also reduced (excluding the surface area of ​​the portion held by the electrode holder 1335 made of insulation and exposed inside the collision chamber 132).

[0047] In this embodiment, by adopting the above-described structure, the chance of free radicals introduced into the collision chamber 132 coming into contact with the metal is reduced compared to the conventional method. Therefore, compared to existing mass spectrometry devices, the disappearance of free radicals introduced into the collision chamber 132 can be suppressed.

[0048] Here, the results of measurements conducted by the inventors to confirm the effect of making the surface area of ​​electrode 1331 smaller than conventionally, as in this embodiment, and covering the inner peripheral surface of collision chamber 132 with insulating sheet 1323, will be described. In this measurement, a conventional mass spectrometry apparatus (an apparatus in which a multipolar ion director is constructed using conventional electrode 2331) and the mass spectrometry apparatus 1 of this embodiment (an apparatus in which a multipolar ion director 133 is constructed using electrode 1331 of this embodiment) were used to irradiate oleic acid having a single double bond with oxygen free radicals to induce a reaction, and a dissociation method (Oxygen Attachment Dissociation: OAD) was performed. The intensities of the precursor ions and product ions were measured respectively. The measurement conditions (oxygen free radical generation conditions, etc.) were the same in both measurements.

[0049] As described in Patent Document 2, reacting precursor ions derived from molecules having hydrocarbon chains containing unsaturated bond (double bond) sites with oxygen free radicals allows the precursor ions to dissociate at the unsaturated bond sites. In this assay, the precursor ions dissociate at the single double bond present in oleic acid, generating product ions. Therefore, the reaction efficiency of the precursor ions can be determined based on the ratio of the intensity of the product ions to the intensity of the precursor ions. This reaction efficiency reflects the concentration of oxygen free radicals in the collision chamber 132.

[0050] Figure 8 This indicates the measurement result. For example... Figure 8 As shown, in existing mass spectrometry devices, the reaction efficiency of precursor ions is about 1%, while in the mass spectrometry device 1 of this embodiment, it is increased to about 10%. This reflects that by covering the inner peripheral surface of the collision chamber 132 with an insulating material and constructing a multipolar ion guide 133 with the electrode 1331 of the above embodiment, the disappearance of oxygen free radicals due to contact with the metal in the collision chamber 132 is suppressed, and the concentration of oxygen free radicals in the collision chamber 132 is increased. Furthermore, it also reflects that in existing mass spectrometry devices, free radicals introduced near the outlet of the collision chamber disappear upon contact with the inner peripheral surface of the collision chamber or the electrode constituting the multipolar ion guide, while in the mass spectrometry device 1 of this embodiment, free radicals introduced into the collision chamber 132 do not disappear due to contact with the metal and diffuse uniformly throughout the interior of the collision chamber 132.

[0051] In existing mass spectrometry devices, when oxidizing free radicals such as oxygen free radicals are introduced, the free radicals adhere to the electrode surface near the free radical inlet, forming oxides that easily form a locally insulating oxide film on the electrode surface. Applying voltage to the electrode while this locally formed insulating oxide film results in charge-up, which can easily cause disturbances in the electric field generated by the multipolar ion guide, sometimes leading to a decrease in ion transport efficiency or ion capture efficiency. In contrast, in the mass spectrometry device 1 of this embodiment, the free radicals introduced into the collision chamber 132 diffuse uniformly throughout the chamber, thus suppressing the electric field disturbances caused by localized oxidation, resulting in improved ion transport efficiency or ion capture efficiency compared to conventional methods.

[0052] Furthermore, in existing technologies, free radicals with reducing capabilities, such as hydrogen free radicals, are introduced into the collision chamber to reduce and remove the insulating oxide film formed on the electrode surface, thereby cleaning the electrode. However, since the introduced free radicals disappear upon contact with the collision chamber or electrode surface near the free radical inlet, the effect of removing the insulating oxide film remains limited to the vicinity of the free radical inlet, making it difficult to fully restore the basic performance of the mass spectrometer. In contrast, in the mass spectrometer 1 of this embodiment, the free radicals introduced into the collision chamber 132 diffuse uniformly throughout the interior of the collision chamber 132, thus cleaning the entire electrode and obtaining the desired performance. The inventors conducted experiments in both existing mass spectrometers and the mass spectrometer of this embodiment, using a copper electrode with an entirely oxidized surface to construct a multipolar ion guide 133, and introducing hydrogen free radicals into the collision chamber 132. The results showed that in existing mass spectrometers, only the portion of the copper oxide on the electrode surface near the free radical inlet was reduced, while in the mass spectrometer 1 of this embodiment, the copper oxide distributed throughout the entire electrode was reduced and removed.

[0053] In the above embodiment, the surface area of ​​the electrode is reduced by cutting off the central portion of the substrate, but other methods can also be used. For example, such as... Figure 9 As shown, the exposed area of ​​the metal can also be reduced by covering a portion of the central portion 2333 of the existing electrode 2331 (the portion removed in the electrode 1331 of this embodiment) with an insulating material 3337 (an insulating sheet or the like). Examples of suitable insulating materials include resins such as polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyoxymethylene (POM), polyimide (PI), and polybenzimidazole (PBI). Even when using such an electrode 3331, the same effect as when using the electrode 1331 of the above embodiment can be obtained.

[0054] The above embodiment is an example and can be appropriately modified in accordance with the spirit of the present invention.

[0055] In the above embodiments, an insulating sheet 1323 is used to cover the inner peripheral surface of the metal collision chamber 132. However, insulating tape or seals can also be attached to the inner peripheral surface of the collision chamber 132 (e.g., Non-Patent Document 6), or an insulating coating treatment (polyimide coating, fluoropolymer coating, etc.) can be applied to the inner peripheral surface of the collision chamber 132 (e.g., Non-Patent Documents 7-9). Alternatively, the collision chamber 132 itself can also be made of an insulating material (e.g., ceramic).

[0056] In this embodiment, a structure is adopted in which a multipolar ion guide 133 is constructed using electrodes 1331 with a smaller surface area than before, and at least a portion of the inner peripheral surface of the collision chamber 132 is covered with an insulating material. However, a structure that satisfies both of these requirements is preferred, but not necessary in this invention. Even with only one of these structures, a sufficient effect of suppressing the disappearance of free radicals in the collision chamber 132 can be expected.

[0057] In the above embodiment, a mass spectrometry device equipped with a Q-TOF type mass separation unit is used, but any mass separation unit can be used. Furthermore, in the above embodiment, an ion source equipped with an ESI probe 101 for generating ions from a liquid sample is used, but other atmospheric pressure ion sources such as an APCI probe can also be used. Alternatively, an ion source that generates ions in a vacuum atmosphere can also be used. Furthermore, an ion source that generates ions from gaseous or solid samples can also be used. Furthermore, in the above embodiment, a collision chamber 132 is used to enable the precursor ions to react with free radicals, but other reaction chambers such as a three-dimensional ion trap can also be used.

[0058] The above-described embodiment is a mass spectrometry device, but the same structure can also be used in an ion mobility analyzer that separates ions based on their mobility.

[0059] In the above embodiment, the radical generation unit 4 utilizes inductively coupled plasma to generate radicals from the feed gas, but capacitively coupled plasma can also be used to generate radicals from the feed gas. Furthermore, the same structure described above can also be used in mass spectrometry apparatuses equipped with a radical generation unit that generates radicals by introducing a feed gas into a heated discharge tube (e.g., Non-Patent Document 10).

[0060] In the above embodiments, the precursor ions react with free radicals. However, by using active particles other than free radicals, such as ozone or metastable particles, the precursor ions can also be dissociated at specific sites. These active particles, like free radicals, are easily destroyed upon contact with metals. Therefore, by employing the same structure as in the above embodiments, the same effects can be obtained when using these active particles. Furthermore, metastable particles refer to atoms (metastable atoms) or molecules (metastable molecules) in a long-lived excited state.

[0061] [Way] For those skilled in the art, it will be obvious that the above exemplary embodiments are specific examples of the following methods.

[0062] (Item 1) An ion analysis apparatus according to one aspect of the present invention includes: A reaction chamber, at least a portion of which is formed of an insulating material on its inner circumferential surface, through which precursor ions derived from the sample components are introduced; and The active particle introduction section generates active particles from the raw material gas and introduces the active particles into the reaction chamber.

[0063] In existing mass spectrometry devices, most of the active particles introduced into the reaction chamber recombine with the metal atoms constituting the inner circumferential surface of the reaction chamber and disappear. In contrast, in the ion analysis device of the first claim, at least a portion of the inner circumferential surface of the reaction chamber is composed of an insulating material. The recombination coefficient between the active particles and the insulating material is lower than that between the active particles and the metal; therefore, even if the active particles introduced into the reaction chamber come into contact with molecules of the insulating material constituting the inner circumferential surface of the reaction chamber, their probability of disappearance is low. Thus, compared to existing mass spectrometry devices, the disappearance of active particles introduced into the reaction chamber can be suppressed.

[0064] (Item 2) The ion analysis apparatus of the second item, in the ion analysis apparatus of the first item, wherein the reaction chamber is constructed by covering at least a portion of the inner circumferential surface of a cylindrical body made of metal with an insulating material.

[0065] The ion analysis device in item 2 can be simply constructed by covering the inner circumferential surface of a metal cylindrical body used in existing mass spectrometry devices with an insulating material.

[0066] (Item 3) The ion analysis apparatus of item 3, in either item 1 or item 2, further comprises: A multipolar ion guide, comprising multiple electrodes arranged around an ion optical axis that serves as the central axis of the flight path of ions in the reaction chamber. The plurality of electrodes are formed by removing a portion of a substrate, which is a plate or column, except for the portion facing the ion optical axis, so that its surface area is reduced compared to that substrate.

[0067] In the ion analysis device of item 3, by removing a portion of a substrate that is approximately plate-shaped or approximately columnar with the same shape as the existing electrode, the surface area exposed in the reaction chamber is reduced, thereby reducing the chance of free radicals coming into contact with the metal and suppressing the disappearance of free radicals.

[0068] (Item 4) The ion analysis apparatus of item 4, in addition to the ion analysis apparatus of item 1 or 2, also includes: A multipolar ion guide, comprising multiple electrodes arranged around an ion optical axis that serves as the central axis of the flight path of ions in the reaction chamber. At least a portion of the surface of the plurality of electrodes, excluding the portion facing the ion optical axis, is covered with an insulating material.

[0069] In the ion analysis apparatus of item 4, at least a portion of the surface of the conventionally used generally plate-shaped or generally columnar electrode, except for the portion facing the ion optical axis, is covered with an insulating material. Therefore, the exposure of the metal portion in the reaction chamber is reduced, the chance of free radicals coming into contact with the metal is reduced, and the disappearance of free radicals can be suppressed.

[0070] [Explanation of Labels in the Attached Image] 1...Mass spectrometer 10...Ionization chamber 100...Vacuum chamber 101...ESI probe 11...First intermediate vacuum chamber 12...Second intermediate vacuum chamber 13...First analysis chamber 132...Collision chamber 1321...Opening 1322...Tube connection component 1323...Insulating sheet 133...Multipolar ion guide 1331...Electrode 1332...Incision 1333...Central portion 1334...Removed portion 1335...Electrode holder 1336...Hole 14...Second analysis chamber 3331...Electrode 3337...Insulator 4...Free radical generation section 41...Plasma generation section 410...Discharge tube 4101...Free radical generation chamber 411...Helical antenna 412...Outer conductor section 413, 415...Permanent magnet 414...Housing 416...Microwave supply connector 417...Light source 418...Photodetector 420...Resonator adjustment mechanism 46...Microwave power supply 48...Raw material gas supply source 61...CID gas supply source 7...Control / processing section 71...Storage section 72...Analysis execution section 81...Input section 82...Display section C...Ion optical axis.

Claims

1. An ion analysis device, characterized in that, have: A reaction chamber, at least a portion of which is formed of an insulating material on its inner circumferential surface, through which precursor ions derived from the sample components are introduced; and The active particle introduction section generates active particles from the raw material gas and introduces the active particles into the reaction chamber.

2. The ion analysis apparatus according to claim 1, characterized in that, The reaction chamber is constructed by covering at least a portion of the inner circumferential surface of a cylindrical body made of metal with an insulating material.

3. The ion analysis apparatus according to claim 1, characterized in that, It also has: A multipolar ion guide, comprising multiple electrodes arranged around an ion optical axis that serves as the central axis of the flight path of ions in the reaction chamber. The plurality of electrodes are formed by removing a portion of a substrate, which is a plate or column, except for the portion facing the ion optical axis, so that its surface area is reduced compared to that substrate.

4. The ion analysis apparatus according to claim 1, characterized in that, It also has: A multipolar ion guide, comprising multiple electrodes arranged around an ion optical axis that serves as the central axis of the flight path of ions in the reaction chamber. At least a portion of the surface of the plurality of electrodes, excluding the portion facing the ion optical axis, is covered with an insulating material.

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