Ion analyzing device

Abstract

To provide an ion analyzing device for generating product ions by reacting precursor ions derived from sample components with active particles such as radicals and analyzing the product ions, an appropriate amount of active particles which matches the combination of the precursor ions and the active particles being supplied to a reaction chamber.SOLUTION: An ion analyzing device (1) includes a reaction chamber (132) into which precursor ions derived from sample components are introduced, an active particle generation unit (4) that generates active particles from a raw material gas, and an active particle transport unit (4102) that transports the active particles generated in the active particle generation chamber to the reaction chamber and has a high resistance region (4103) provided between the active particle generation chamber and the reaction chamber, the high resistance region having a higher flow resistance than the active particle generation chamber.SELECTED DRAWING: Figure 4

Description

[Technical field]

[0001] The present invention relates to an ion analyzer that generates and measures product ions by reacting precursor ions derived from sample components with active particles such as radicals. [Background technology]

[0002] MS / MS analysis using a mass spectrometer is performed to identify components contained in a sample and to estimate the molecular structure of unknown components. In MS / MS analysis, ions derived from the sample components (precursor ions) are introduced into a reaction chamber, where the precursor ions are dissociated to generate product ions, which are then mass-separated and detected. Based on the partial structure information obtained from the mass-to-charge ratio of the detected product ions, the sample components can be identified and their molecular structures estimated.

[0003] One method of dissociating precursor ions is to react them with radical species such as hydrogen radicals and oxygen radicals (e.g., Patent Documents 1 to 4). For example, when precursor ions derived from a peptide are dissociated by reacting them with radicals, product ions that reflect the structure of the peptide, such as the amino acid sequence, are generated. By analyzing the mass spectrum in which such product ions are observed, the structure of the peptide can be deduced.

[0004] Non-Patent Documents 1 and 2 describe radical generators used in carrying out the radical attachment dissociation method. These radical generators include a straight tube made of a dielectric material and a helical antenna wound around the outer periphery of the straight tube. By supplying high-frequency power to the helical antenna while circulating a source gas such as hydrogen gas or water vapor inside the straight tube, plasma of the source gas is generated to generate radicals. Patent Document 4 describes a mass spectrometer in which one end of the straight tube is connected to a reaction chamber to supply radicals to the reaction chamber. In this mass spectrometer, precursor ions are supplied to the reaction chamber and reacted with the radicals to dissociate them and generate product ions. The reaction chamber is provided with an electrode (multipole ion guide) that defines the flight path of the ions, and the generated product ions are transported to the rear stage by the electric field formed by the multipole ion guide. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2019-191081 A [Patent Document 2] International Publication No. 2019 / 155725 [Patent Document 3] International Publication No. 2021 / 095105 [Patent Document 4] International Publication No. 2022 / 059247 [Non-patent literature]

[0006] [Non-Patent Document 1] Yuji Simabukuro and 4 others, "Tandem Mass Spectrometry of Peptide Ions by Microwave Excited Hydrogen and Water Plasmas", Analytical Chemistry, 2018, Vol.90, No.12, pp.7239-7245 [Non-Patent Document 2] Yuji Simabukuro, "Comprehensive Study on the Low-energy Atomic Hydrogen Beam: From Production to Velocity Distribution Measurement" (Doctoral thesis), [online], [Retrieved June 15, 2023], Doshisha University Academic Repository, 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 Document 3] Kyoto University, Faculty of Engineering, Department of Physics and Engineering, "Energy Science and Engineering Design Exercises and Experiments 2", Special Edition, A-8 Conductance of a Circular Straight Tube, [online], [Retrieved July 11, 2023], Internet<URL: http: / / www.nucleng.kyoto-u.ac.jp / people / ikuji / edu / vac / app-A / conduct.html> [Non-Patent Document 4] Kyoto University, Faculty of Engineering, Department of Physics Engineering, "Energy Science and Engineering Design Exercises and Experiments 2", Special Edition, A-9 Conductance of Various Shapes, [online], [Retrieved July 11, 2023], Internet<URL: http: / / www.nucleng.kyoto-u.ac.jp / people / ikuji / edu / vac / app-A / orifice.html> [Non-Patent Document 5] Hidenori Takahashi and 6 others, "Hydrogen Attachment / Abstraction Dissociation (HAD) of Gas-Phase Peptide Ions for Tandem Mass Spectrometry," Analytical Chemistry, 2016, Vol. 88, No. 7, pp. 3810-3816 Summary of the Invention [Problem to be solved by the invention]

[0007] The efficiency with which radicals contribute to the reaction of precursor ions and radicals varies depending on the combination of precursor ions and radical species. If the amount of radicals supplied to the reaction chamber is insufficient, the reaction is unlikely to occur, and product ions are unlikely to be generated. On the other hand, if the amount of radicals supplied to the reaction chamber is excessive, unreacted radicals will adhere to the electrode placed in the reaction chamber and contaminate the electrode surface. For example, when oxygen radicals or hydroxyl radicals adhere to the electrode surface, oxides are generated and charged up. This causes a disturbance in the electric field in the reaction chamber, which reduces the transport efficiency of ions in the reaction chamber and reduces the measurement sensitivity of product ions. Therefore, it is preferable to set the flow rate of the raw material gas supplied to the radical generation chamber so that an appropriate amount of radicals is generated according to the combination of precursor ions and radical species.

[0008] However, in conventional mass spectrometers, one end of the straight tube is connected to a reaction chamber, which is a high vacuum. When the flow rate of the source gas is reduced to generate a small amount of radicals, the pressure inside the straight tube drops to close to the pressure of the reaction chamber, making it difficult to generate plasma or maintain the plasma state. This poses the problem that it is difficult to supply the appropriate amount of radicals to the reaction chamber according to the combination of sample components and radical species.

[0009] Here, as a typical example, the case where precursor ions are dissociated by reacting with radicals has been described, but the same problem as described above occurs when precursor ions are dissociated using other active particles such as ozone or metastable particles.

[0010] The problem that the present invention aims to solve is to supply an appropriate amount of active particles according to the combination of precursor ions and active particles to a reaction chamber in an ion analyzer that generates and analyzes product ions by reacting precursor ions derived from sample components with active particles such as radicals. [Means for solving the problem]

[0011] The ion analyzer according to the present invention, which has been made to solve the above problems, is a reaction chamber into which precursor ions derived from a sample component are introduced; an active particle generating unit that supplies a raw material gas to an active particle generating chamber and generates active particles from the raw material gas; an active particle transport section for transporting the active particles generated in the active particle generation chamber to the reaction chamber, the active particle transport section including a high resistance region between the active particle generation chamber and the reaction chamber, the high resistance region having a flow path higher than that of the active particle generation chamber; Equipped with. Effect of the Invention

[0012] In the ion analysis device according to the present invention, a raw material gas is supplied to an active particle generation chamber, and active particles are generated from the raw material gas. The active particles may include radicals, ozone, metastable particles, and the like. The active particle generation chamber is provided inside a straight tube made of a dielectric material, for example, with a helical antenna wound around its outer periphery. The active particles generated in the active particle generation chamber are transported by an active particle transport section to a reaction chamber into which precursor ions derived from sample components are introduced. The active particle transport section is provided with a high resistance region between the active particle generation chamber and the reaction chamber, the high resistance region having a flow path resistance higher than that of the active particle generation chamber.

[0013] In a conventional mass spectrometer, one end of a straight tube having an active particle generation chamber inside is connected to a reaction chamber, and the resistance of the flow path from the active particle generation chamber to the reaction chamber is constant, so that when the flow rate of the raw material gas is reduced, the pressure inside the straight tube (active particle generation chamber) drops to near the pressure of the reaction chamber, making it difficult to generate plasma or maintain the plasma state. In contrast, in the ion analyzer according to the present invention, a high resistance region with a higher flow resistance than the active particle generation chamber is provided in the active particle transport section, and the pressure of the active particle generation chamber is unlikely to drop, so that even if the flow rate of the raw material gas flowing into the reaction chamber is reduced, plasma can be generated and maintained in the active particle generation chamber. Therefore, an appropriate amount of active particles according to the combination of the sample components and the active particles can be supplied to the reaction chamber. [Brief description of the drawings]

[0014] [Figure 1] 1 is a schematic diagram of an embodiment of a mass spectrometer according to the present invention; [Diagram 2] FIG. 2 is a cross-sectional view showing a schematic configuration of a radical generating unit in the present embodiment. [Diagram 3] FIG. 4 is a side view showing a schematic configuration of a tip end of a radical generator in the present embodiment. [Figure 4] 4A and 4B are diagrams comparing the tip of a conventional discharge tube with the tip of a discharge tube according to the present embodiment. [Diagram 5] 11A to 11C are diagrams illustrating another embodiment in which a high resistance region is formed. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] An embodiment of a mass spectrometer according to the present invention will be described below with reference to the drawings. In the drawings used in the following description, the scale of each component is appropriately changed from the actual ratio and some components are omitted in order to make the configuration of the main components in the embodiment easier to understand.

[0016] <Schematic configuration of mass spectrometer 1> 1 shows a schematic configuration of a mass spectrometer 1 according to one embodiment of the present invention. The mass spectrometer 1 of this embodiment is a quadrupole time-of-flight (Q-TOF) mass spectrometer equipped with an atmospheric pressure ion source. This mass spectrometer 1 can be used as a liquid chromatograph mass spectrometer by connecting a liquid chromatograph (LC) to the upstream stage.

[0017] The mass spectrometer 1 of this embodiment has an ionization chamber 10 and a vacuum chamber 100. The inside of the ionization chamber 10 is under an approximately atmospheric pressure atmosphere. The inside of the vacuum chamber 100 is divided into a plurality of compartments (four compartments in this embodiment), which are, in order from the side closest to the ionization chamber 10, 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 to a vacuum by a vacuum pump (rotary pump and / or turbo molecular pump) not shown, and has a multi-stage differential pumping system configuration in which the degree of vacuum increases in sequence from the ionization chamber 10, which is under an approximately atmospheric pressure atmosphere, to the second analysis chamber 14, which is under a high vacuum atmosphere.

[0018] An electrospray ionization (ESI) probe 101 that applies an electric charge to a liquid sample and sprays it is installed in the ionization chamber 10. A liquid sample containing sample components separated in, for example, an LC column (not shown) is introduced into the ESI probe 101.

[0019] The ionization chamber 10 and the first intermediate vacuum chamber 11 are in communication with each other through a thin-diameter desolvation tube 102 heated by a heat source (not shown). In the first intermediate vacuum chamber 11, an ion guide 111 is arranged, which is composed of a plurality of rod electrodes arranged to surround an ion optical axis C, which is the central axis of the ion flight path, and which focuses ions in the vicinity of the ion optical axis C.

[0020] The first intermediate vacuum chamber 11 and the second intermediate vacuum chamber 12 are separated by a skimmer 112 having a small hole at the top. The second intermediate vacuum chamber 12 also includes an ion guide 121 that is composed of a plurality of rod electrodes arranged to surround the ion optical axis C and focuses ions in the vicinity of the ion optical axis C.

[0021] In the first analysis chamber 13, a quadrupole mass filter 131 that separates ions according to their mass-to-charge ratio (m / z), a collision cell 132 equipped with a multipole ion guide 133 therein, and an ion transport electrode 134 for transporting ions that have passed through the collision cell 132 to a subsequent stage are arranged along the ion optical axis C. The quadrupole mass filter 131 and the multipole ion guide 133 each comprise a plurality of rod electrodes. The ion transport electrode 134 comprises a plurality of ring-shaped electrodes.

[0022] An opening 1321 for inserting the discharge tube 410 of the radical generation unit 4 is provided on the wall surface of the collision cell 132. The configuration of the radical generation unit 4 will be described later. A cylindrical tube connection member 1322 is provided so that one end surrounds the opening 1321. A collision induced dissociation (CID) gas supply source 61 is also connected to the collision cell 132. A valve 62 for adjusting the flow rate of a CID gas (e.g., an inert gas such as argon gas) supplied from the CID gas supply source 61 to the collision cell 132 is provided in a flow path connecting the CID gas supply source 61 and the collision cell 132.

[0023] In the collision cell 132, a dissociation method can be performed in which precursor ions are dissociated by reacting with radicals such as oxygen radicals supplied from the radical generation unit 4, and a collision-induced dissociation (CID) method can be performed in which precursor ions are accelerated by imparting energy to them while entering the collision cell 132 and dissociated by colliding with a CID gas.

[0024] The second analysis chamber 14 is equipped with an ion transport electrode 141 for transporting the ions incident from the first analysis chamber 13, an orthogonal acceleration section 142 having a pair of a push electrode and a pull electrode arranged opposite to each other across the optical axis C of the ions, an acceleration electrode 143 for accelerating the ions sent out to the flight space by the orthogonal acceleration section 142, a reflectron electrode 144 for forming a return trajectory of the ions in the flight space, an ion detector 145, and a flight tube 146 for forming the flight space therein. The ion detector 145 is, for example, an electron multiplier tube or a multichannel plate.

[0025] The mass spectrometer 1 of this embodiment further comprises a control / processing unit 7, an input unit 81, and a display unit 82. The control / processing unit 7 comprises a memory unit 71. The memory unit 71 stores information on analytical conditions (measurement conditions, analysis methods, etc.) for various compounds. The control / processing unit 7 comprises an analysis execution unit 72 as a functional block. The analysis execution unit 72 sets analytical conditions according to instructions from a user, and performs measurement of a sample and analysis of the measurement data based on the set analytical conditions. The control / processing unit 7 is constituted by, for example, a general-purpose personal computer (PC), and various functions are realized by executing dedicated control / processing software installed on the computer with a processor.

[0026] <Schematic configuration of radical generating unit 4> FIG. 2 is a cross-sectional view of a main part, which shows a schematic structure of the plasma generating section 41 in the radical generating section 4. The radical generating section 4 corresponds to one aspect of the active particle generating section in the present invention. The configuration of the radical generating section 4 shown in FIG. 2 is the same as that of the prior application (Patent Application No. 2022-164919) by the present inventor, except for the configuration of the end portion on the downstream side (the side of the collision cell 132) of the discharge tube 410. FIG. 3 is a schematic cross-sectional view of the downstream end portion of the discharge tube 410, and FIG. 4 shows a comparison between the discharge tube in a conventional mass spectrometer and the discharge tube 410 of this embodiment.

[0027] The plasma generating unit 41 generates plasma of the raw material gas supplied from the raw material gas supply source 48, and introduces radicals generated in the plasma into the collision cell 132. For example, water vapor, oxygen gas, nitrogen gas, dry air, and hydrogen gas are used as the raw material gas. The microwave power supply 46 supplies power for generating the plasma to a helical antenna 411 (described later). The amount of the raw material gas supplied from the raw material gas supply source 48 is adjusted by a mass flow controller including a valve 40 provided in a flow path connecting the raw material gas supply source 48 and the discharge tube 410.

[0028] The plasma generating unit 41 includes a discharge tube 410 made of quartz or aluminum oxide, which is an insulator and a dielectric, a helical antenna 411, which is a belt-shaped conductor wound in a spiral shape around the discharge tube 410, an outer conductor 412, which is a conductor coaxial with the discharge tube 410 and has a cylindrical opening with an inner diameter one size larger than the outer diameter of the discharge tube 410, a permanent magnet 413 embedded in the outer conductor 412, a casing 414 that holds the outer conductor 412, and a permanent magnet 415 arranged at the bottom of the casing 414. For the helical antenna 411, for example, a metal such as copper, preferably a material close to pure copper having high conductivity and formability (oxygen-free copper, tough pitch copper, etc.), is used. In addition, it is preferable that the surface is gold-plated to prevent oxidation.

[0029] The casing 414 is provided with a microwave supply connector 416. The casing 414 is also provided with a light source 417 that emits ultraviolet light inside the discharge tube 410 and a photodetector 418 that detects the light emission of the plasma generated inside the discharge tube 410. The light source 417 is turned on / off based on a control signal transmitted from the analysis execution unit 72. In this embodiment, the light source 417 emits deep ultraviolet light with a wavelength of 275 nm or less. When light in this wavelength band is irradiated onto the discharge tube 410 made of quartz or aluminum oxide, electrons are emitted from the wall surface of the discharge tube 410. These electrons induce plasma. For example, a UV-LED can be used as the light source 417. For the photodetector 418, one that is not sensitive to the wavelength band of the light emitted from the light source 417 and is sensitive only to the wavelength band of the light emitted from the plasma inside the discharge tube 410 is used. For example, a photodiode can be used as the photodetector 418. The detection signal of the photodetector 418 is transmitted to the control and processing unit 7 and stored in the memory unit 71. The analysis execution unit 72 judges the presence or absence of plasma generation by, for example, comparing the magnitude of the detection signal of the photodetector 418 with a predetermined threshold value.

[0030] The discharge tube 410 is a raw material introduction tube into which raw material gas is introduced from the raw material gas supply source 48, and within the discharge tube 410, a region in which the helical antenna 411 is wound and where ultraviolet light is irradiated from the light source 417 constitutes a radical generation chamber 4101, and the region downstream of the radical generation chamber 4101 constitutes a radical transport section 4102. The radical transport section 4102 corresponds to one embodiment of the active particle transport section in the present invention. As shown in Fig. 3, the discharge tube 410 has an outer diameter of 6 mm and an inner diameter of 4 mm, and an opening 4103 having an inner diameter of 0.6 mm and a length of 1.5 mm is provided at the downstream end of the discharge tube 410.

[0031] The microwave supply connector 416 is a coaxial connector, and is connected to the microwave power supply 46 via a coaxial cable. The conductive wire of the coaxial connector is connected to one end of the helical antenna 411. The outer conductor 412 is grounded. A part of the helical antenna 411 and the outer conductor 412 are electrically connected via a resonator adjustment mechanism 420, and the helical antenna 411 is grounded at the connection position. The helical antenna 411, the outer conductor 412, the resonator adjustment mechanism 420, etc. form an electron cyclotron resonance (ECR) resonator. The resonator adjustment mechanism 420 is used to adjust the ECR resonator. The configuration of the resonator adjustment mechanism 420 is the same as that described in Patent Document 3, so a detailed description will be omitted. The microwave power supply 46 supplies power to this resonator via the coaxial cable and the microwave supply connector 416.

[0032] In the plasma generating unit 41 of the present embodiment, local inductively coupled discharge and electron cyclotron resonance are used to generate and maintain plasma. In this plasma generating unit 41, the density of the plasma can be increased and stabilized by ECR.

[0033] A substantially disk-shaped magnet holder 51 is attached to the bottom surface of the casing 414. The casing 414 and the magnet holder 51 function as a holding member 50 that holds the discharge tube 410. An opening is formed in the center of the magnet holder 51 through which the discharge tube 410 and the guide member 52 are inserted. The guide member 52 is a cylindrical member that is arranged coaxially with the discharge tube 410 and on the outer periphery of the discharge tube 410, and a compression spring 56 that expands and contracts in the axial direction of the discharge tube 410 is attached to the outer periphery of the guide member 52. A cylindrical protector 53 is provided at the tip of the guide member 52. The guide member 52 and the protector 53 are arranged on the outer periphery of the tip portion of the discharge tube 410 that is exposed from the magnet holder 51, and the tip of the protector 53 is located outward from the tip of the discharge tube 410. As a result, the guide member 52 , the protector 53 and the compression spring 56 function as a tube protection member 54 that protects the outer periphery and the tip of the portion of the discharge tube 410 that is exposed from the holding member 50 .

[0034] <Attachment of the radical generation unit 4 to the collision cell 132> The collision cell 132 is fixed to the vacuum chamber 100 at a portion not shown. Openings are formed in the walls of the vacuum chamber 100 and the collision cell 132, and a tube connection member 1322 is inserted into both openings. The tube connection member 1322 is a cylindrical member having a bottom surface with a through hole formed therein, and its bottom is attached to the opening 1321 of the collision cell 132. The diameter of the through hole formed in 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. The inlet of the tube connection member 1322 is formed in a tapered shape that widens toward the inlet end. The outer circumferential tip of the protector 53 is also formed in a tapered shape.

[0035] The operation of attaching the radical generation unit 4 to the collision cell 132 is similar to that of the above-mentioned prior application, so a detailed explanation will be omitted; however, in the radical generation unit 4, the outside of the discharge tube 410 is protected by a protector 53 until the tip of the discharge tube 410 enters the inside of the collision cell 132, thereby preventing the discharge tube 410 from being damaged when attaching the radical generation unit 4.

[0036] Next, an example of the operation of MS / MS analysis in the mass spectrometer 1 of this embodiment will be described. Here, a case will be described in which precursor ions derived from components contained in a liquid sample are dissociated by a dissociation method in which they react with radicals and a collision-induced dissociation method to generate product ions and measure them.

[0037] When the user issues an instruction to start measurement, the analysis execution unit 72 operates the above-mentioned components as follows to measure the sample.

[0038] Prior to the introduction of the liquid sample, each chamber in the vacuum chamber 100 and the inside of the discharge tube 410 are evacuated to a predetermined pressure. Then, the valve 62 is opened and the CID gas is supplied to the collision cell 132. When the inside of the collision cell 132 reaches a predetermined pressure, preparation for measurement is completed.

[0039] The ESI probe 101 sprays the supplied liquid sample into the ionization chamber 10 while imparting an electric charge to the liquid sample. The sample components in the sprayed charged droplets are ionized as the droplets are broken down into fine particles and the solvent evaporates. The generated ions derived from the sample components are carried by a gas flow formed by the pressure difference between the ionization chamber 10 and the first intermediate vacuum chamber 11 and are drawn into the first intermediate vacuum chamber 11. The ions that have entered the first intermediate vacuum chamber 11 fly along the ion optical axis C, and pass through the ion guide 111, the small holes in the skimmer 112, and the ion guide 121 in this order, before being sent to the first analysis chamber 13 and entering the quadrupole mass filter 131.

[0040] A voltage consisting of a superimposed DC voltage and a radio frequency voltage is applied from a power source (not shown) to the multiple rod electrodes that make up the quadrupole mass filter 131. Ions (precursor ions) having a specific mass-to-charge ratio according to this applied voltage selectively pass through the quadrupole mass filter 131 and enter the collision cell 132.

[0041] When collision induced dissociation is performed in the collision cell 132, a downward potential gradient is formed from the outlet of the quadrupole mass filter 131 toward the inlet of the collision cell 132, which imparts collision energy to the precursor ions, accelerating them and causing them to enter the collision cell 132. In this embodiment, regardless of whether dissociation by reaction with radicals or collision induced dissociation is being performed, the valve 62 is always maintained at a predetermined opening during measurement, and the inside of the collision cell 132 is maintained at a constant pressure by the CID gas supplied at a predetermined flow rate from the CID gas supply source 61. The precursor ions accelerated and entering the collision cell 132 collide with CID gas molecules, causing the precursor ions to dissociate, generating product ions.

[0042] When dissociation by reaction with radicals is performed in the collision cell 132, the above-mentioned potential gradient is not formed (or the gradient is made small), and the precursor ions are made to enter the collision cell 132 without imparting collision energy to the precursor ions. Radicals are supplied to the collision cell 132 from the radical generator 4, and the precursor ions introduced into the collision cell 132 react with the radicals and dissociate, generating product ions. As described above, in this embodiment, the CID gas is supplied to the collision cell 132 even when dissociation by reaction with radicals is performed, but since the precursor ions are not accelerated, the precursor ions are hardly dissociated even when colliding with CID gas molecules.

[0043] The product ions generated in the collision cell 132 are converged by the action of the electric field formed by the multipole ion guide 133 as they pass through the collision cell 132, pass through the ion transport electrode 134 and the ion transport electrode 141 in that order, and enter the orthogonal acceleration section 142.

[0044] A pulse voltage is applied to the electrodes of the orthogonal acceleration unit 142 from a power source (not shown) at a predetermined timing. The application of this pulse voltage causes an electric field to be formed between the push electrode and the pull electrode, and the ions introduced into the orthogonal acceleration unit 142 are ejected in a direction substantially perpendicular to the ion optical axis C. The ions ejected from the orthogonal acceleration unit 142 are accelerated by the acceleration electrode 143 and introduced into a flight space in a flight tube 146. The ions then fly back in a reflected electric field formed by the reflectron electrode 144 and reach an ion detector 145. The flight time of the ions from the time they leave the orthogonal acceleration unit 142 to the time they reach the ion detector 145 depends on the velocity of the ions, and the ion velocity depends on the mass-to-charge ratio of the ions. The analysis execution unit 72 creates a time-of-flight spectrum showing the relationship between the flight time and the ion intensity based on the detection signal obtained by the ion detector 145, creates a mass spectrum by converting the flight time into a mass-to-charge ratio value, and identifies and quantifies the components contained in the liquid sample.

[0045] The mass spectrometer 1 of this embodiment is characterized by the configuration of the radical production section 4, particularly the configuration of the discharge tube 410. This point will be described below.

[0046] In the radical generation section of a conventional mass spectrometer, a raw material gas is circulated inside a straight tube made of a dielectric material, and the raw material gas is turned into plasma inside the straight tube to generate radicals. On the other hand, in this embodiment, as shown in Figures 3 and 4, an opening 4103 having a diameter smaller than the inner diameter of the discharge tube 410 is formed at the downstream end. The portion where this opening 4103 is formed is a part of the flow path through which the radicals generated in the radical generation chamber 4103 flow, and functions as a high resistance region provided in the radical transport section 4102.

[0047] The efficiency with which radicals contribute to the reaction between precursor ions and radicals varies depending on the combination of precursor ions and radical species. If the amount of radicals supplied to the collision cell 132 is insufficient, the reaction is unlikely to occur, and product ions are unlikely to be generated. On the other hand, if the amount of radicals supplied to the collision cell 132 is excessive, unreacted radicals adhere to the surface of the multipole ion guide 133 in the collision cell 132, contaminating the electrode surface. For example, when oxygen radicals or hydroxyl radicals adhere to the electrode surface, oxides are generated and charged up. This causes a disturbance in the electric field in the collision cell 132, which reduces the ion transport efficiency and reduces the measurement sensitivity of the product ions. Therefore, it is preferable to set the flow rate of the raw material gas supplied to the radical generation chamber 4101 so that an appropriate amount of radicals is generated according to the combination of precursor ions and radical species.

[0048] For example, when water vapor is used as a raw material gas and mixed with hydrogen gas, the standard flow rates are within the range of 0.1 to 1 sccm for each of water vapor and hydrogen gas, and the flow rates for maintaining plasma after radical generation are, for example, 0.3 sccm for water vapor and 0.2 sccm for hydrogen gas. When using this mixed gas, it is water vapor that generates radicals that contribute to the reaction, and hydroxyl radicals and oxygen radicals generated from water vapor dissociate precursor ions. On the other hand, hydrogen radicals generated from hydrogen gas reduce and remove oxides formed on the electrode surface due to the attachment of hydroxyl radicals and oxygen radicals. Also, only water vapor may be used as the raw material gas, and in that case, the standard flow rate is within the range of 0.1 to 1 sccm, and the flow rate for maintaining plasma after radical generation is, for example, 0.3 sccm. Furthermore, when hydrogen gas is used as the raw material gas, the standard flow rate is within the range of 0.1 to 1 sccm, and the flow rate for maintaining plasma after radical generation is, for example, 0.5 sccm. When hydrogen gas is used as the source gas, hydrogen radicals generated from the hydrogen gas are reacted with the precursor ions.

[0049] In general, once the raw material gas is turned into plasma, the plasma state can be maintained by supplying the raw material gas at a flow rate lower than that required to generate the plasma. However, in conventional mass spectrometers, one end of the straight discharge tube is connected to a collision cell, which is a high vacuum. Therefore, when the flow rate of the raw material gas is reduced, the pressure in the radical generation chamber inside the discharge tube drops to near the pressure of the collision cell, making it difficult to generate plasma or maintain the plasma state. This problem is particularly noticeable when hydrogen gas is used as the raw material gas.

[0050] Increasing the flow rate of the source gas makes it easier to generate and maintain plasma, but as mentioned above, if the amount of radicals supplied to the collision cell is excessive, the multipole ion guide in the collision cell is easily contaminated, and the consumption of the source gas increases, resulting in higher costs.

[0051] In addition, in the measurement in which dissociation by reaction with radicals and collision-induced dissociation are switched between as described above, if the supply of CID gas to the collision cell is stopped during dissociation by reaction with radicals, a waiting time occurs until the pressure of the CID gas in the collision cell stabilizes when switching from dissociation by reaction with radicals to collision-induced dissociation. Although it is possible to continue supplying CID gas to the collision cell during dissociation by reaction with radicals, in conventional mass spectrometers, the CID gas flows into the inside of the discharge tube, where it becomes plasma and removes oxides and other substances adhering to the inner wall surface of the discharge tube. When such substances flow into the collision cell, they oxidize the electrode surface in the collision cell, causing a disturbance in the electric field.

[0052] In contrast, in the mass spectrometer 1 of this embodiment, a high resistance region is provided at the downstream end of the discharge tube 410, so that the source gas introduced into the discharge tube 410 is unlikely to flow into the collision cell 132, and the flow rate of the source gas can be easily adjusted to generate an appropriate amount of radicals according to the combination of precursor ions and radicals. Furthermore, even if the flow rate of the source gas is small, the pressure in the radical generation chamber 4101 is unlikely to decrease, making it easy to generate and maintain radicals. Furthermore, the consumption of the source gas can be suppressed, thereby reducing costs.

[0053] Furthermore, in the mass spectrometer 1 of this embodiment, even if the CID gas used for collision induced dissociation is supplied to the collision cell 132 while dissociation by reaction with radicals is being performed, the CID gas hardly flows into the radical generation chamber 4101, and no plasma of the CID gas is generated. Therefore, when performing a measurement in which dissociation by reaction with radicals and collision induced dissociation are performed, there is no need to stop the supply of CID gas to the collision cell 132, and the above-mentioned waiting time can be eliminated to improve the measurement efficiency.

[0054] Based on the above technical idea, the discharge tube 410 of this embodiment determines the diameter and length of the opening 4103 so that an appropriate flow path resistance (the reciprocal of conductance) is obtained. The smaller the diameter of the opening 4103 is, and the longer the opening 4103 is, the larger the flow path resistance is. When the flow path resistance is large, the pressure in the radical generation chamber 4101 is less likely to be reduced, but on the other hand, it becomes difficult to introduce the radicals generated in the radical generation chamber 4101 into the collision cell 132. In addition, if the cross-sectional area of ​​the opening 4103 is too small or the opening 4103 is too long, the radicals generated in the radical generation chamber 4101 are likely to collide with the wall surface of the opening 4103 and disappear. Therefore, it is preferable to determine the diameter and length of the opening 4103 based on the balance between these parameters, for example, the pressure of the collision cell 132, the volume of the radical generation chamber 4101, the flow rate of the raw material gas that can generate an appropriate amount of radicals, and other parameters.

[0055] Here, an actual calculation example regarding the conductance will be described. Conductance C in a molecular flow is expressed by the following formula (see formula (11) in Non-Patent Document 3). C=a 3 / L [Liter / s]=a 3 / L / 1000 [m 3 / s] …(1) In the above formula, a is the radius of the aperture (mm) and L is the length of the aperture (mm).

[0056] The conductance of a straight pipe with an inner diameter of φ4 mm and a length of 50 mm (a conventional configuration without an opening 4103) is: C=2 3 / 50 / 1000=1.6×10 -4 [m 3 / s] …(2) Converting this to flow rate Q (sccm) gives Q = C × P = 1.6 × 10 -4 ×P [Pa·m 3 / s] ≒ 9.5 × 10 -2 ×P [sccm] …(3) In the above formula, P is the pressure (Pa) of the radical generation chamber 4101. Using the above formula (3), when the flow rate is 0.1 sccm, P = 1.1 (Pa), when the flow rate is 0.5 sccm, P = 5.3 (Pa), and when the flow rate is 1.9 sccm, P = 20 (Pa).

[0057] Moreover, the conductance C of the opening is expressed by the following formula (see formula (5)' in Non-Patent Document 4). C=11.6A [L / s] …(4) In the above formula, A is the cross-sectional area of ​​the opening (cm 2 In the above embodiment, when the diameter of the opening 4103 is φ0.3 mm, C = 11.6 × (0.015) 2 ×π≒0.008 [L / s]=8×10 -6 [m 3 / s] …(5) Converting this to flow rate Q (sccm) gives Q = C × P = 8 × 10 -6 ×P [Pa·m 3 / s] ≒ 5 × 10 -3 ×P [sccm] …(6) Therefore, for example, when the flow rate is 0.5 sccm, P=5.3 (Pa) in the conventional configuration, whereas when opening 4103 having a diameter of φ0.3 mm is formed, P=100 (Pa). Also, in the conventional configuration, a flow rate of 1.9 sccm is required to achieve P=20 (Pa), whereas when opening 4103 having a diameter of φ0.3 mm is formed, P=20 (Pa) at a flow rate of 0.1 sccm.

[0058] The inventors also actually measured the pressure inside the discharge tube 410 when the flow rate of hydrogen gas was set to 0.1 sccm for both the conventional configuration and the above embodiment with the opening 4103 having a diameter of φ0.6 mm. The pressure was 1.1 Pa for the conventional configuration, whereas it was 4.7 Pa for the present embodiment with the opening 4103. This result is consistent with the result calculated using the above formula (3) (P≒1.1 (Pa) at a flow rate of 0.1 sccm for the conventional configuration) and the result calculated using the above formula (6) (P≒5 (Pa) at a flow rate of 0.1 sccm when the opening 4103 having a diameter of φ0.6 mm is provided). Thus, by adopting the configuration of the above embodiment with the opening 4103 having a diameter of φ0.6 mm, the internal pressure of the discharge tube 410 (pressure of the radical generation chamber 4101) can be increased to four times or more than that of the conventional configuration.

[0059] Furthermore, in the apparatus of this embodiment, the plasma state could be maintained even when the valve 40 was closed (the set value of the raw material gas flow rate by the mass flow controller was set to 0). This is presumably because even when the set value of the mass flow controller was set to 0, a small amount of raw material gas flowed into the radical generation chamber 410 due to an internal leak of the valve 40 (mass flow controller). The internal leak specification of the mass flow controller used here is less than 0.1 sccm. In other words, when the set value of the mass flow controller was set to 0, the flow rate of the raw material gas flowing from the raw material gas supply source through the mass flow controller into the radical chamber 410 was less than 0.1 sccm. By providing the opening 4103 as in this embodiment, the plasma state can be maintained even at a low flow rate of less than 0.1 sccm.

[0060] As a result of the above-mentioned investigation, the inventors have determined that when the length of the opening 4103 is set to 1.5 mm, the cross-sectional area is 0.007 mm 2 More than 3.1mm 2 It has been found that it is preferable to set the diameter of the opening 4103 to 0.1 mm or more and 2.0 mm or less when the cross section of the opening 4103 is circular. The cross-sectional shape of the opening 4103 is not limited to a circle, and may be other shapes (polygon, ellipse, etc.).

[0061] The discharge tube 410 in the above embodiment is produced by crimping and welding a 1.5 mm thick quartz plate with an opening 4103 to the end of a straight tube, but it may be produced by other methods. For example, a discharge tube similar to the above embodiment can be produced by flat-sealing a quartz tube and forming an opening at the end.

[0062] Also, the high resistance region may be formed in a member other than the member forming the radical generation chamber. For example, as shown in FIG. 5, the high resistance region can be formed by attaching an attachment 911 to the end of a discharge tube (straight tube) 910. The attachment 911 is a member having a base portion 9111 having an outer diameter approximately equal to the outer diameter of the discharge tube 910 and a cylindrical portion 9112 having an outer diameter slightly smaller than the inner diameter of the discharge tube 910, and a first opening 9113 and a second opening 9114 having an inner diameter smaller than the inner diameter of the first opening are formed in the center of the member. It is difficult to perform processing to form a hole with a high aspect ratio, such as a small diameter (φ0.6 mm) and a length of 5 mm. Therefore, in this example, a small and short second opening 9114 (for example, φ0.6 mm, length 0.5 mm) is formed as a portion that substantially controls the flow path resistance, and the first opening 9113 is made larger in diameter (φ1.0 mm) than that, making the processing easier. A groove is provided on the side circumference of the cylindrical portion 9112, and by attaching an O-ring 912 to this groove and inserting an attachment 911 into the discharge tube 910, the gap between the inner surface of the discharge tube 910 and the outer surface of the attachment 911 is airtightly sealed.

[0063] The above embodiment is merely an example and can be modified as appropriate in accordance with the spirit of the present invention.

[0064] In the above embodiment, the mass spectrometer is equipped with a Q-TOF type mass separator, but any mass separator can be used. In addition, in the above embodiment, the ion source is equipped with an ESI probe 101 that generates ions from a liquid sample, but other atmospheric pressure ion sources such as an APCI probe can be used. Alternatively, an ion source that generates ions in a vacuum atmosphere can be used. Furthermore, an ion source that generates ions from a gas or solid sample can be used. Furthermore, in the above embodiment, a collision cell 132 is used to react precursor ions with radicals, but other reaction chambers such as a three-dimensional ion trap can be used.

[0065] Although the above embodiment is a mass spectrometer, a similar configuration can also be adopted in an ion mobility spectrometer that separates ions according to their mobility.

[0066] In the above embodiment, the light source 417 is used to irradiate the discharge tube 410 made of quartz or aluminum oxide with ultraviolet light. However, the plasma may be generated without using the light source 417 .

[0067] In the above embodiment, the radical generating unit 4 generates radicals from the raw material gas by inductively coupled plasma, but radicals may be generated from the raw material gas by capacitively coupled plasma. Also, a similar configuration to the above can be used in a mass spectrometer equipped with a radical generating unit (e.g., Non-Patent Document 5) that generates radicals by introducing a raw material gas into a heated discharge tube.

[0068] In the above embodiment, the precursor ion reacts with the radical, but the precursor ion can be dissociated at a specific position by using active particles other than radicals, such as ozone or metastable particles. The same configuration as the above embodiment can be adopted when using active particles other than radicals. Note that metastable particles refer to atoms (metastable atoms) or molecules (metastable molecules) in a long-life excited state.

[0069] [Aspects] It will be apparent to those skilled in the art that the above-described exemplary embodiments are illustrative of the following aspects.

[0070] (Section 1) An ion analyzer according to one aspect of the present invention comprises: a reaction chamber into which precursor ions derived from a sample component are introduced; an active particle generating unit that supplies a raw material gas to an active particle generating chamber and generates active particles from the raw material gas; an active particle transport section for transporting the active particles generated in the active particle generation chamber to the reaction chamber, the active particle transport section including a high resistance region between the active particle generation chamber and the reaction chamber, the high resistance region having a flow path higher than that of the active particle generation chamber; Equipped with.

[0071] In the ion analyzer according to paragraph 1, a raw material gas is supplied to an active particle generation chamber, and active particles are generated from the raw material gas. The active particle generation chamber is provided inside a straight tube made of a dielectric material, for example, with a helical antenna wound around its outer periphery. The active particles generated in the active particle generation chamber are transported by an active particle transport section to a reaction chamber into which precursor ions derived from sample components are introduced. This active particle transport section is provided, between the active particle generation chamber and the reaction chamber, with a high resistance region having a flow path resistance higher than that of the active particle generation chamber.

[0072] In a conventional mass spectrometer, one end of a straight tube having a radical generation chamber inside is connected to a reaction chamber, and the resistance of the flow path from the radical generation chamber to the reaction chamber is constant, so that when the flow rate of the raw material gas is reduced, the pressure inside the straight tube drops to near the pressure of the reaction chamber, making it difficult to generate plasma or maintain the plasma state. In contrast, in the ion analyzer according to paragraph 1, a high resistance region with a higher flow resistance than the active particle generation chamber is provided in the active particle transport section, and the pressure in the active particle generation chamber is less likely to drop, so that even if the flow rate of the raw material gas flowing into the reaction chamber is reduced, plasma can be generated and maintained in the active particle generation chamber. Therefore, an appropriate amount of active particles according to the combination of the sample components and active particles can be supplied to the reaction chamber.

[0073] (Section 2) The ion analyzer according to paragraph 2 is the ion analyzer according to paragraph 1, The radical generation chamber is provided inside a straight pipe, and the high resistance region is a flow path having a cross-sectional area smaller than that of the straight pipe.

[0074] In the ion analyzer according to the second aspect, a high resistance region having an appropriate level of flow channel resistance can be easily provided simply by adjusting the cross-sectional area of ​​the flow channel.

[0075] (Section 3) The ion analyzer according to paragraph 3 is an ion analyzer according to paragraph 2, The cross-sectional area is 0.007 mm 2 More than 3.1mm 2 The following is the result.

[0076] In the ion analyzer according to paragraph 3, the cross-sectional area of ​​the flow path is set to 0.007 mm 2 By setting the cross-sectional area of ​​the flow path to 3.1 mm or more, it is possible to prevent the radicals from colliding with the wall of the flow path and being lost. 2 By setting the above as follows, it is possible to reduce the fluctuation in pressure in the radical generation chamber and easily adjust the flow rate of the source gas so as to generate an appropriate amount of radicals according to the combination of precursor ions and radicals. Note that, when the cross section of the opening is circular, the above cross-sectional area corresponds to a diameter of 0.1 mm or more and 2.0 mm or less. The cross-sectional shape of the opening is not limited to a circle, and may be other shapes (polygon, ellipse, etc.).

[0077] (Section 4) The ion analyzer according to paragraph 4 is an ion analyzer according to paragraph 2 or 3, The end of the straight pipe is processed so that the high resistance region is integrally formed with the straight pipe.

[0078] (Section 5) The ion analyzer according to paragraph 5 is an ion analyzer according to paragraph 2 or 3. A mounting member having a flow passage with a diameter smaller than the inner diameter of the straight pipe is attached to the end of the straight pipe.

[0079] In the ion analyzer according to paragraph 2 or 3, the high resistance region may be formed in a member constituting the straight pipe (paragraph 4), or may be formed in a member other than the member constituting the straight pipe (paragraph 5). The former can be produced, for example, by fixing (for example, by crimping and welding) a plate material having an opening that will become the high resistance region to the end of the straight pipe, or by processing (for example, by flat sealing) the end of the straight pipe. The latter can be produced, for example, by attaching an attachment having an opening that will become the high resistance region to the center of a member having a base portion having a diameter approximately equal to the outer diameter of the straight pipe and a cylindrical portion having a diameter slightly smaller than the inner diameter of the straight pipe, to the end of the straight pipe. In either case, it is preferable to use a member constituting the active particle generation chamber and the active particle transport portion, at least whose inner surface is made of a dielectric material. This can reduce the proportion of active particles that are lost when they collide with the wall surface, compared to the case of using metal or the like.

[0080] (Section 6) The ion analyzer according to paragraph 6 is an ion analyzer according to any one of paragraphs 1 to 5, further comprising: a collision gas supply source that supplies a collision gas for collision-induced dissociation of the precursor ions to the reaction chamber; an analysis execution unit that controls the operation of the active particle generation unit and the collision gas supply source, and executes a measurement in which the precursor ions are dissociated by reaction with the active particles and collision induced dissociation to generate product ions, the analysis execution unit generating active particles in the active particle generation unit only during the execution of the reaction with the active particles, and continuing to introduce collision gas from the collision gas supply source into the reaction chamber regardless of the reaction with the active particles or the collision induced dissociation; Equipped with.

[0081] In conventional ion analyzers, when performing measurements that switch between reactions with active particles and collision-induced dissociation, it was necessary to stop the supply of collision gas to the collision cell while the reaction with the active particles was occurring. As a result, when switching from reactions with active particles to collision-induced dissociation, a waiting time was required until the pressure of the collision gas in the collision cell stabilized. However, the ion analyzer according to paragraph 6 continues to supply collision gas, eliminating the above-mentioned waiting time and improving measurement efficiency. [Explanation of symbols]

[0082] 1...Mass spectrometer 10…Ionization chamber 100…Vacuum chamber 101…ESI probe 11…First intermediate vacuum chamber 12...Second intermediate vacuum chamber 13…1st analysis room 131...Quadrupole mass filter 132…Collision cell 1321…Aperture 1322...Pipe connection parts 133...Multipole ion guide 134...Ion transport electrode 14…Second analysis room 141...Ion transport electrode 142...Orthogonal acceleration section 143...acceleration electrode 144...Reflectron electrode 145…Ion detector 146…Flight tube 4... Radical generation section 40…Valve 41...Plasma generating section 410...discharge tube 4101…Radical generation room 4102... Radical transport unit 4103…Aperture 411…Helical antenna 412...Outer conductor part 413...Permanent magnet 414…Casing 415...Permanent magnet 416...Microwave supply connector 417...Light source 418...Photodetector 420…Resonator adjustment mechanism 46...Microwave power supply 48…Source gas supply source 50...Retaining member 51...Magnet holder 52...Guide member 53…Protector 54...Pipe protection member 61…CID gas supply source 62…Valve 7…Control and processing section 71...Storage section 72…Analysis Execution Department 910...discharge tube 911…Attachment 9111...Base 9112…Cylindrical part 9113…First opening 9114…Second opening 912…O-ring C…Ion optical axis< / url:>

Claims

1. a reaction chamber into which precursor ions derived from a sample component are introduced; an active particle generating unit that supplies a raw material gas to an active particle generating chamber and generates active particles from the raw material gas; an active particle transport section for transporting the active particles generated in the active particle generation chamber to the reaction chamber, the active particle transport section including a high resistance region between the active particle generation chamber and the reaction chamber, the high resistance region having a flow path higher than that of the active particle generation chamber; An ion analyzer comprising:

2. 2. The ion analyzer according to claim 1, wherein the active particle generation chamber is provided inside a straight tube, and the high resistance region is a flow path having a cross-sectional area smaller than that of the straight tube.

3. The cross-sectional area is 0.007 mm 2 More than 3.1mm 2 The ion analyzing device according to claim 2 , wherein:

4. The ion analyzing device according to claim 2 , wherein the high resistance region is formed integrally with the straight tube by processing an end portion of the straight tube.

5. 3. The ion analyzer according to claim 2, wherein a mounting member having a flow passage with a diameter smaller than an inner diameter of the straight tube is attached to an end of the straight tube.

6. moreover, a collision gas supply source that supplies a collision gas for collision-induced dissociation of the precursor ions to the reaction chamber; an analysis execution unit that controls the operation of the active particle generation unit and the collision gas supply source, and executes a measurement in which the precursor ions are dissociated by reaction with the active particles and collision induced dissociation to generate product ions, the analysis execution unit generating active particles in the active particle generation unit only while the reaction with the active particles is being executed, and continuing to introduce a predetermined amount of collision gas from the collision gas supply source into the reaction chamber regardless of whether the reaction with the active particles or the collision induced dissociation is being executed; The ion analyzer of claim 1 .

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