Radical generator

Abstract

To reduce the possibility of undesired product ions being generated, undesired mass shifts being generated, and unintended discharges being generated in a mass spectrometer configured to perform ion dissociation by radical reaction by placing a reaction cell in place of a collision cell of an existing mass spectrometer and connecting a radical generation unit to the reaction cell.SOLUTION: In a mass spectrometer, a radical reaction device (4) used in place of a collision cell that dissociates ions generated from a sample, includes a radical generation portion (40) that generates a predetermined type of radical, a reaction cell (42) having a radical inlet into which radicals generated in the radical generation portion are introduced, a vacuum gauge (423) that measures the degree of vacuum in the space in which the reaction cell is placed, and a radical generation control portion (63) that operates the radical generation portion when the degree of vacuum measured by the vacuum gauge satisfies predetermined conditions.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to a radical production device used for producing and measuring product ions by reacting precursor ions derived from sample components with 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, it is possible to identify the sample components and estimate their molecular structure.

[0003] One method of dissociating precursor ions is to react them with radical species such as hydrogen radicals, oxygen radicals, and hydroxyl radicals. The method of dissociating precursor ions by reacting them with hydrogen radicals is called HAD (Hydrogen Attachment / Abstraction Dissociation), and the method of dissociating precursor ions by reacting them with oxygen radicals or hydroxyl radicals is called OAD (Oxygen Attachment Dissociation). For example, by reacting precursor ions derived from peptides with radicals, peptides can be specifically dissociated at the positions where amino acids are bonded (for example, Patent Document 1). Also, for example, by reacting precursor ions derived from sample components having hydrocarbon chains with radicals, molecules having hydrocarbon chains can be specifically dissociated at the positions of double bonds (for example, Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2018 / 186286 [Patent Document 2] International Publication No. 2019 / 155725 [Patent Document 3] International Publication No. 2022 / 059247 Summary of the Invention [Problem to be solved by the invention]

[0005] In conventional mass spectrometers, precursor ions derived from sample components are introduced into a collision cell, where they collide with molecules of an inert gas such as argon, causing collision-induced dissociation (CID) of the precursor ions to generate product ions. The collision cell of a mass spectrometer can be removed for cleaning the internal electrodes, etc., and in order to make it possible to perform HAD and OAD in existing mass spectrometers, it is being considered to place a reaction cell with a radical inlet formed in it instead of the collision cell and connect a radical generator to it.

[0006] Since existing mass spectrometers equipped with a collision cell are not expected to perform HAD or OAD, when a radical generator is attached to the existing mass spectrometer and operated, a radical generation control unit that controls the operation of the radical generator must be provided independently of the existing mass spectrometer. However, the radical generation control unit cannot check the state of the mass spectrometer to which it is attached, particularly the state of gas introduction into the reaction cell and the degree of vacuum in the reaction cell. Therefore, if radicals are introduced while CID gas is introduced, undesired radicals derived from the CID gas may be generated, resulting in the generation of product ions due to unintended reactions, or the desired ion cooling state may not be obtained, resulting in mass deviation. In addition, if radicals are introduced into the reaction cell when the degree of vacuum is insufficient, discharge may occur and the device may be destroyed.

[0007] The problem that the present invention aims to solve is to reduce the possibility of undesired product ions being generated, undesired mass shifts being generated, or unintended discharges being generated in a mass spectrometer that is configured to be capable of performing ion dissociation by radical reactions by placing a reaction cell in place of the collision cell of an existing mass spectrometer and connecting a radical generation unit to the reaction cell. [Means for solving the problem]

[0008] The present invention, which has been made to solve the above problems, is a radical reaction device used in place of a collision cell that dissociates ions generated from a sample in a mass spectrometer, comprising: A radical generator that generates a predetermined type of radical; a reaction cell having a radical inlet into which the radicals generated in the radical generation section are introduced; a vacuum gauge for measuring a degree of vacuum in a space in which the reaction cell is disposed or inside the reaction cell; a radical generation control unit that operates the radical generation unit when the degree of vacuum measured by the vacuum gauge satisfies a predetermined condition; Equipped with. Effect of the Invention

[0009] The radical reaction apparatus according to the present invention is used in place of a collision cell when performing ion dissociation by radical reaction using an existing mass spectrometer. When using the apparatus, the collision cell of the existing mass spectrometer is removed and a reaction cell is placed in its place. In this radical reaction apparatus, a predetermined type of radical generated in the radical generation unit is introduced into the reaction cell, and precursor ions derived from sample components are reacted with the radicals in the reaction cell to generate product ions. The radical reaction apparatus according to the present invention is provided with a vacuum gauge that measures the degree of vacuum in the space in which the reaction cell is placed or inside the reaction cell, and when the degree of vacuum measured by the vacuum gauge satisfies a predetermined condition, the radical generation control unit operates the radical generation unit. This predetermined condition is set to a condition that ensures that no CID gas is introduced and that the vacuum exhaust system is operating normally. In the radical reaction apparatus according to the present invention, it is possible to reduce the possibility that undesired product ions are generated by introducing radicals in a state in which CID gas is introduced, that the desired ion cooling state is not obtained and mass shift occurs, and that unintended discharge occurs by introducing radicals into the reaction cell in a state in which the degree of vacuum is insufficient. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a diagram showing the configuration of a main part of a mass spectrometer equipped with an embodiment of a radical reaction device according to the present invention. [Diagram 2] FIG. 2 is a diagram showing the configuration of a main part of the radical reaction device of the present embodiment. [Diagram 3] FIG. 2 is a diagram showing the configuration of a reaction cell of a radical reaction apparatus according to the present invention (and a collision cell of an existing mass spectrometer). [Figure 4] FIG. 2 is a cross-sectional view taken along line AA′ of the first analysis chamber, illustrating the arrangement of a vacuum gauge in the mass spectrometer of the present embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, an embodiment of a radical reaction device according to the present invention will be described with reference to the drawings.

[0012] <Configuration of mass spectrometer 1> 1 shows the main configuration of a mass spectrometer 1 equipped with an embodiment of a radical reaction device according to 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.

[0013] 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 in an atmosphere of approximately atmospheric pressure. The inside of the vacuum chamber 100 is divided into a plurality of compartments (five 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 third intermediate vacuum chamber 13, a first analysis chamber 14, and a second analysis chamber 15. The first intermediate vacuum chamber 11, the second intermediate vacuum chamber 12, the third intermediate vacuum chamber 13, and the first analysis chamber 14 are evacuated by a first turbomolecular pump 51, and the second analysis chamber 15 is evacuated by a second turbomolecular pump 52. A back pump 53, which is a roughing pump, is connected to the exhaust ports of the first turbomolecular pumps 51 and 52 through an exhaust line 54. This constitutes a multi-stage differential exhaust system in which the degree of vacuum increases from the ionization chamber 10, which is in an atmosphere of approximately atmospheric pressure, toward the second analysis chamber 15, which is in a high vacuum atmosphere.

[0014] 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.

[0015] 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 roughly rod-shaped 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.

[0016] 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 and the third intermediate vacuum chamber 13 are separated by a wall surface having a small hole for passing ions. The second intermediate vacuum chamber 12 and the third intermediate vacuum chamber 13 each include an ion lens 121 and an ion lens 131, which are configured with a plurality of rod electrodes arranged to surround the ion optical axis C and focus ions near the ion optical axis C.

[0017] In the first analysis chamber 14, a quadrupole mass filter 141 including a main rod electrode that is composed of four rod electrodes and separates ions according to their mass-to-charge ratio (m / z), a reaction cell 42 having a multipole ion guide 43 (see the vertical cross-sectional view on the left in FIG. 3 and the B-B' cross-sectional view on the right in FIG. 3) composed of eight plate-shaped electrodes therein, and an ion transport electrode 144 for transporting ions that have passed through the reaction cell 42 to a subsequent stage are arranged along the ion optical axis C. The ion transport electrode 144 is composed of a plurality of ring-shaped electrodes. In addition, as shown in the A-A' cross-sectional view in FIG. 4, two vacuum gauges (vacuum gauge 423 and main body vacuum gauge 145) are arranged at the same position in the direction of the ion optical axis C in the first analysis chamber 14. The vacuum gauge 423 is arranged above the vacuum chamber 100, and the main body vacuum gauge 145 is arranged on the side of the vacuum chamber 100.

[0018] An opening 421 is provided in the wall of the reaction cell 42, and a cylindrical connecting member 422 is arranged to surround the opening 421. A collision induced dissociation (CID) gas source 55 is also connected to the reaction cell 42. A third mass flow controller 56 is provided in a flow path connecting the CID gas source 55 and the reaction cell 42, for adjusting the flow rate of the CID gas (e.g., an inert gas such as argon gas) supplied from the CID gas source 55 to the reaction cell 42. The CID gas can also be used as a cooling gas for cooling ions that have entered the reaction cell 42. Alternatively, the cooling gas may be introduced into the reaction cell 42 from a flow path separate from that for the CID gas.

[0019] The radical production part 40 is connected to an opening 421 in the wall of the reaction cell 42. The radical production part 40, the reaction cell 42, a vacuum gauge 423, and a second control part 6 (see FIG. 2) described later are included in the radical reaction device 4. The configuration of the radical reaction device 4 will be described later.

[0020] In the reaction cell 42, a dissociation method can be performed in which precursor ions are dissociated by radicals such as oxygen radicals supplied from the radical generation unit 40, and a collision-induced dissociation (CID) method can be performed in which precursor ions are accelerated by imparting energy to them and then entering the collision cell 142, where they are dissociated by colliding with a CID gas.

[0021] The second analysis chamber 15 is equipped with an ion transport electrode 151 for transporting the ions incident from the first analysis chamber 14, an orthogonal acceleration section 152 having a pair of push-out and pull-in electrodes arranged opposite to each other across the ion optical axis C, a second acceleration section 153 for accelerating the ions sent out to the flight space by the orthogonal acceleration section 152, a reflectron electrode 154 for forming a return trajectory of the ions in the flight space, an ion detector 155, and a flight tube 156 for forming the flight space therein. The ion detector 155 is, for example, an electron multiplier or a multichannel plate.

[0022] The mass spectrometer 1 of this embodiment further comprises a control / processing unit 7, an input unit 73, and a display unit 74. 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 composed of, for example, a general-purpose personal computer (PC), and various functions are realized by executing dedicated control / processing software installed on the computer in a processor.

[0023] <Configuration of radical reaction device 4> The mass spectrometer 1 of this embodiment is characterized in that it is configured by installing a radical reaction device 4 instead of the collision cell of an existing mass spectrometer. The existing mass spectrometer also has a configuration similar to that of the reaction cell 42 of the radical reaction device 4 (see FIG. 3), that is, a collision cell 142 having a multipole ion guide 143 therein. However, the collision cell 142 does not have an opening corresponding to the opening 421 of the reaction cell 42. When using the radical reaction device 4 of this embodiment, first, the collision cell 142 and the multipole ion guide 143 are removed from the vacuum chamber 100, and the reaction cell 42 is placed at the position of the collision cell 142. Then, a vacuum gauge 423 is attached to the vacuum chamber 100. As shown in the A-A' cross section in FIG. 4, the attachment position of the vacuum gauge 423 is the same as that of the main body vacuum gauge 145 in the direction along the ion optical axis C.

[0024] 2 shows the configuration of the radical reaction device 4 of this embodiment. As described above, the radical reaction device 4 includes the reaction cell 42, the radical generation unit 40 connected to the reaction cell 42, the vacuum gauge 423, and the second control unit 6 that controls the operation of the radical generation unit 40. The radical generation unit 40 and the vacuum gauge 423 are attached to the upper surface of a plate-shaped base material 424. The reaction cell 42 is attached to the lower surface of the base material 424 via a connecting member 422. The outlet end of the quartz tube 41 of the radical generation unit 40 is fixed in a state of being inserted into the opening 421 via the connecting member 422, and the base material 424 is attached to a predetermined position of the vacuum chamber 100, so that the radical generation unit 40, the reaction cell 42, and the vacuum gauge 423 can be attached to the vacuum chamber 100 at the same time.

[0025] The radical generating unit 40 has a quartz tube 41, the inside of which is used as a radical generating chamber, around which a helical antenna is wound, and the inside of the quartz tube 41 (radical generating chamber) is evacuated to a predetermined pressure and high frequency power is supplied to the helical antenna to generate plasma of the raw material gas and generate radicals. For example, the radical generating unit 40 of this embodiment may suitably be one having the configuration described in Patent Document 3, which generates radicals from plasma of the raw material gas by vacuum discharge.

[0026] A source gas supply flow path is connected to the inlet end of the quartz tube 41. The source gas supply flow path branches into two via a flow path switching valve 48, and one flow path is connected to a first mass flow controller 44 and a hydrogen gas supply port 45 that supplies hydrogen gas from outside the housing of the mass spectrometer. The other flow path is connected to a second mass flow controller 46 and a water tank 47. The radical generator 40 generates hydrogen radicals from hydrogen gas supplied from the hydrogen gas supply port 45, or generates hydroxyl radicals or oxygen radicals from water vapor supplied from the water tank 47.

[0027] The second control unit 6 includes a storage unit 61. The storage unit 61 stores information about radical generation conditions, such as the flow rates during use and the high-frequency power supplied to the helical antenna, for each of hydrogen gas and water vapor, and information about the criteria for operating the radical generation unit 40 (the value of the output signal from the vacuum gauge 423 or the degree of vacuum). The second control unit 6 also includes, as functional blocks, a calibration execution unit 62 and a radical generation control unit 63. Both of these functional blocks are realized by the computer processor executing dedicated programs that have been installed in advance. An input unit 64 and a display unit 65 are also connected to the second control unit 6.

[0028] <Use of radical reaction device 4> When using the radical reaction device 4, first, as described above, the collision cell 142 provided in the existing mass spectrometer is removed, and the base material 424 is attached to a predetermined position in the vacuum chamber 100. As described above, the radical generation section 40, the vacuum gauge 423, and the reaction cell 42 are disposed above and below the base material 424 and are integrated with the base material 424, so that these sections are attached to the vacuum chamber 100 at once by simply attaching the base material 424. At this time, as shown in the A-A' cross section of the first analysis chamber 14 in FIG. 4, the main body vacuum gauge 145 and the vacuum gauge 423 are attached to the same position in the direction of the ion optical axis C.

[0029] Inside the first analysis chamber 14, the pressure may vary depending on the position in the direction along the ion optical axis C. By attaching the vacuum gauge 423 and the main body vacuum gauge 145 at the same position in the direction along the ion optical axis C as described above, the vacuum gauge 423 and the main body vacuum gauge 145 measure the vacuum degree of a space at the same pressure. Preferably, the vacuum gauge 423 and the main body vacuum gauge 145 are disposed adjacent to each other. Also, preferably, the vacuum gauge 423 and the main body vacuum gauge 145 are disposed equidistantly from the gas inlet from the CID gas supply source 55 to the reaction cell 42, the opening 421 through which radicals are introduced from the radical production unit 40, and / or the CID gas supply port.

[0030] After the reaction cell 42, the radical generation unit 40, and the vacuum gauge 423 are installed, when the user performs a predetermined input operation to instruct calibration of the vacuum gauge, the calibration execution unit 62 calibrates the vacuum gauge 423. The calibration of the vacuum gauge 423 is performed by matching the value of the output signal from the vacuum gauge 423 with the value of the output signal from the main body vacuum gauge 145 in each of a state (first state) in which the inside of the vacuum chamber 100 is evacuated to a predetermined pressure and a state (second state) in which a predetermined flow rate of CID gas is supplied from the CID gas supply source 55 in the first state. Neither the vacuum gauge 423 nor the main body vacuum gauge 145 directly measures the degree of vacuum inside the reaction cell 42, but rather measures the degree of vacuum in the first analysis chamber 14. However, when CID gas is supplied into the reaction cell 42 in the second state, the CID gas flows out from the ion inlet and ion outlet of the reaction cell 42 into the first analysis chamber 14, and the degree of vacuum in the first analysis chamber 14 decreases (the pressure increases) by that amount compared to the first state. Therefore, a difference occurs in the degree of vacuum in first analysis chamber 14 between the first state and the second state, and the introduction state of the CID gas can be confirmed based on this difference.

[0031] When calibrating the vacuum gauge 423, the pressure obtained from the value of the output signal of the vacuum gauge 423 may be calibrated to match the pressure obtained from the value of the output signal of the main vacuum gauge 145, but the characteristics of the output signal of the vacuum gauge may differ depending on the type of gas present in the measurement space. Therefore, it is preferable to calibrate the vacuum gauge by matching the values ​​of the output signal (e.g., current) from the vacuum gauge. The values ​​of the output signal from the vacuum gauge 423 in the first state and the second state acquired during calibration are stored in the storage unit 61. The first state is a state in which normal evacuation by the first turbo molecular pump 51 is performed, CID gas is not introduced, and radicals can be introduced into the reaction cell 42. Therefore, it is preferable to determine a criterion (the value of the output signal from the vacuum gauge 423 or the degree of vacuum) for operating the radical generator 40 based on the measurement value (the value of the output signal or the degree of vacuum) of the vacuum gauge 423 in the first state. At this time, the measurement value of vacuum gauge 423 may be used as the reference value as is, or a value obtained by allowing some margin for the measurement value of vacuum gauge 423 obtained during calibration (such as a value between the measurement value in the first state and the measurement value in the second state) may be used as the reference value.

[0032] When analyzing a sample, for example, an outlet flow path of a column of a liquid chromatograph is connected to the ESI probe 101. The analysis execution unit 72 controls the operation of each unit except for the radical reaction device 4 based on the analysis conditions stored in the memory unit 71.

[0033] When performing an analysis in which precursor ions derived from sample components are reacted with radicals to generate product ions, the radical generation control unit 63 reads out an output signal from the vacuum gauge 423. Then, when the value of the output signal from the vacuum gauge 423 meets the criteria stored in the memory unit 61, the display unit 65 displays on its screen "Ready for radical introduction OK", indicating that the inside of the reaction cell 42 is in a state in which radicals can be introduced. In response to this, when the user performs an input operation to instruct the introduction of radicals through the input unit 64, the radical generation control unit 63 operates the radical generation unit 40. Specifically, the type of raw material gas (hydrogen gas or water vapor) designated by the user is introduced into the inside of the quartz tube 41 at a predetermined flow rate, and high-frequency power is supplied to the helical antenna wound around the outer periphery of the quartz tube 41. As a result, the raw material gas is turned into plasma and radicals are generated. The generated radicals flow into the reaction cell 42 from the outlet end of the quartz tube 41.

[0034] On the other hand, if the output signal from the vacuum gauge 423 does not satisfy the criteria stored in the memory unit 61, a message such as "Please check the state of the reaction cell" is displayed on the screen of the display unit 65, urging the user to check whether the CID gas has been introduced into the reaction cell 42 and whether the vacuum exhaust system is operating normally. During this time, the radical production control unit 63 stops the radical production unit 40 until the output signal from the vacuum gauge 423 reaches a value satisfying the criteria.

[0035] The components of a sample separated in a liquid chromatograph column are sequentially introduced into the ESI probe 101 and ionized. The ions of the sample components are focused along the ion optical axis C by the ion guide 111 in the first intermediate vacuum chamber 11, and are also focused along the ion optical axis C by the ion lenses 121 and 131 in the second and third intermediate vacuum chambers 12 and 131, respectively, before entering the first analysis chamber 14.

[0036] In the first analysis chamber 14, ions having a predetermined mass-to-charge ratio are selected as precursor ions by the quadrupole mass filter 141. The precursor ions then enter the reaction cell 42 and react with radicals generated in the radical generation section 40 and introduced into the reaction cell 42 to generate product ions. The generated product ions are transported to the second analysis chamber 15 by the ion transport electrode 144.

[0037] In the second analysis chamber 15, the product ions are transported by the ion transport electrode 151 to the orthogonal acceleration section 152. The flight direction of the product ions entering the orthogonal acceleration section 152 is deflected, and the product ions are accelerated by the second acceleration section 153 and enter a flight space. The product ions fly through the flight space at speeds according to their respective mass-to-charge ratios and are detected by the ion detector 155.

[0038] The radical generation control unit 63 acquires the value of the output signal from the vacuum gauge 423 at predetermined intervals even while the above analysis is being performed, and if the value no longer meets a predetermined standard, it stops the operation of the radical generation unit 40 and displays on the screen of the display unit 65 that the operation of the radical generation unit 40 has been stopped.

[0039] In addition, in the mass spectrometer 1, a CID gas can be introduced into the reaction cell 42, and precursor ions derived from the sample components can be subjected to collision-induced dissociation to generate product ions for mass analysis. In this case, the analysis execution unit 72 introduces the CID gas from the CID gas supply source 55 into the reaction cell 42 at a predetermined flow rate based on the analysis conditions stored in the storage unit 71.

[0040] When the measurement is performed by introducing the CID gas into the reaction cell 42 as described above, if the radical generator 40 is operated by mistake to introduce radicals into the reaction cell 42, the CID gas and the radicals react with each other to generate undesired radicals derived from the CID gas, and the radicals may react unintentionally with precursor ions to generate product ions. If product ions are generated by such an unintended reaction, it becomes difficult to analyze the product ion spectrum data obtained by the measurement. In addition, during the analysis of a sample, the precursor ions are cooled in the reaction cell 42 on the assumption that the inside of the first analysis chamber 14 including the reaction cell 42 is at a predetermined vacuum level. However, if the CID gas is introduced into the reaction cell 42, the vacuum level inside the reaction cell 42 decreases, and the desired cooling state of the ions cannot be obtained, which may cause mass deviation. Furthermore, if radicals are introduced into the reaction cell 42 when the reaction cell 42 has an insufficient vacuum level due to the introduction of the CID gas into the reaction cell 42 or the operation of the first turbo molecular pump 51 being defective, discharge may occur and the device may be destroyed.

[0041] In the mass spectrometer 1 of this embodiment, the radical reaction device 4 is provided with a vacuum gauge 423 and a second control unit 6 in addition to the main vacuum gauge 145 and the control / processing unit 7 provided in the existing mass spectrometer. The vacuum gauge 423 is calibrated to match the main vacuum gauge 145, and the radical production control unit 63 operates the radical production unit 40 only when the vacuum gauge 423 indicates that the state inside the reaction cell 42 satisfies a predetermined criterion. The predetermined criterion is a degree of vacuum corresponding to a state in which the first analysis chamber 14 is evacuated to a predetermined degree of vacuum by the first turbo molecular pump 51 and no CID gas is introduced into the reaction cell 42. In this way, in the mass spectrometer 1 of this embodiment, radicals are introduced into the reaction cell 42 only when it is confirmed that the inside of the first analysis chamber 14 is at a degree of vacuum that satisfies the predetermined criterion and that the inside of the reaction cell 42 is in a state in which radicals can be introduced. This reduces the possibility of undesired product ions being generated when radicals are further introduced into the reaction cell 42 while the CID gas has already been introduced, of mass shifts occurring due to an inability to obtain the desired ion cooling state, and of unintended discharges occurring due to radicals being introduced into the reaction cell when the degree of vacuum is insufficient.

[0042] The above embodiment is merely an example and can be modified as appropriate in accordance with the spirit of the present invention.

[0043] In the above embodiment, in a mass spectrometer having a configuration including a quadrupole mass filter 141 and an orthogonal acceleration time-of-flight mass spectrometer, a reaction cell 42 is arranged instead of a collision cell, and radicals are introduced into the reaction cell from a radical generator 40 to form a radical reaction device 4, but the radical reaction device 4 can also be used in mass spectrometers having other configurations in the same manner as above. For example, a radical reaction device 4 having the same configuration as above can also be suitably used in a triple quadrupole mass spectrometer having a front-stage quadrupole mass filter, a collision cell, and a rear-stage quadrupole mass filter.

[0044] In the above embodiment, the radical generator 40 is used to generate radicals from the source gas by vacuum discharge, but other methods of generating radicals may be used. For example, a radical generator that generates radicals by thermally decomposing hydrogen gas or the like may be used. In the above embodiment, the radical generator generates radicals from hydrogen gas and water vapor, but the combination of the source gas and the type of radicals can be changed as appropriate, for example, nitrogen radicals can be generated from nitrogen gas.

[0045] In the above embodiment, vacuum gauge 423 was calibrated by matching the output signal value from vacuum gauge 423 with the output signal value from main body vacuum gauge 145 in each of a first state in which the inside of vacuum chamber 100 is evacuated to a predetermined pressure, and a second state in which a predetermined flow rate of CID gas is supplied from CID gas supply source 55 in the first state. However, it is also possible to introduce CID gas or radical raw material gas with different flow rates into reaction cell 42 to create a plurality of different vacuum degree states, and calibrate vacuum gauge 423 by matching the output signal value from vacuum gauge 423 at each vacuum degree with the output signal value of main body vacuum gauge 145.

[0046] In the above embodiment, the vacuum gauge 423 of the radical reaction device 4 is calibrated to the main vacuum gauge 145 of the existing mass spectrometer. However, when the vacuum gauge 423 is used only to determine whether radicals can be introduced, the vacuum gauge 423 is not calibrated, and the vacuum level of the reaction cell 42 is measured in advance using only the vacuum gauge 423 of the radical reaction device 4 in a state where the first analysis chamber is normally evacuated by the evacuation system and no CID gas is introduced, and the reference value may be set based on the measured value. However, since information on the vacuum level can be used for various controls other than the introduction of radicals, it is preferable to calibrate the vacuum gauge 423 of the radical reaction device 4 to the main vacuum gauge 145 of the existing mass spectrometer as in the above embodiment. In addition, by calibrating the vacuum gauge 423 to the main vacuum gauge 145, the reference value for the vacuum level can be made common to the two vacuum gauges 423 and 145, which simplifies various settings when the radical generation control unit 63 controls the radical generation unit 40, etc. Specifically, for example, when the main body vacuum gauge 145 of an existing mass spectrometer reaches XPa, an error occurs during processing by the analysis execution unit 72 of the control / processing unit 7, so control can be performed such as adjusting the flow rate of the raw material gas (hydrogen gas or water vapor) so that it does not exceed XPa.

[0047] In the above embodiment, the vacuum level of the first analysis chamber 14 (the space in which the reaction cell 42 is disposed) is measured by the vacuum gauge 423 of the radical reaction device 4 and the main body vacuum gauge 145, but if a vacuum gauge can be disposed inside the reaction cell 42, the vacuum gauge may be attached directly to the reaction cell 42 to measure the vacuum level inside the reaction cell 42. In this case, the main body vacuum gauge 145 attached to the collision cell 142 may be temporarily removed from the collision cell 142, and the reaction cell 42, the vacuum gauge 423, and the like may be attached, and then the main body vacuum gauge 145 may be attached to the reaction cell 42.

[0048] [Aspects] It will be apparent to those skilled in the art that the above-described exemplary embodiments are illustrative of the following aspects.

[0049] (Section 1) One aspect of the present invention is a radical reaction device used in place of a collision cell that dissociates ions generated from a sample in a mass spectrometer, comprising: A radical generator that generates a predetermined type of radical; a reaction cell having a radical inlet into which the radicals generated in the radical generation section are introduced; a vacuum gauge for measuring a degree of vacuum in a space in which the reaction cell is disposed or inside the reaction cell; a radical generation control unit that operates the radical generation unit when the degree of vacuum measured by the vacuum gauge satisfies a predetermined condition; Equipped with.

[0050] The radical reaction apparatus according to the first paragraph is used in place of a collision cell when performing ion dissociation by radical reaction using an existing mass spectrometer. When using the apparatus, the collision cell of the existing mass spectrometer is removed and a reaction cell is placed in its place. In this radical reaction apparatus, a predetermined type of radical generated in a radical generation unit is introduced into a reaction cell, and a precursor ion derived from a sample component is reacted with the radical in the reaction cell to generate product ions. The radical reaction apparatus according to the first paragraph is provided with a vacuum gauge that measures the degree of vacuum in the space in which the reaction cell is placed or inside the reaction cell, and when the degree of vacuum measured by the vacuum gauge satisfies a predetermined condition, a radical generation control unit operates the radical generation unit. The predetermined condition is set to a condition that ensures that no CID gas is introduced and that the vacuum exhaust system is operating normally. In the radical reaction apparatus according to the first paragraph, it is possible to reduce the possibility that undesired product ions are generated by introducing radicals in a state where a CID gas is introduced, that the desired cooling state of ions is not obtained and mass shift occurs, and that unintended discharge occurs by introducing radicals into the reaction cell in a state where the degree of vacuum is insufficient.

[0051] (Section 2) The radical reaction apparatus according to the second aspect of the present invention is the radical reaction apparatus according to the first aspect of the present invention, The mass spectrometer includes a body vacuum gauge that is attached to a space in which the collision cell is disposed or to an inside of the collision cell; moreover, The vacuum gauge is calibrated to the main body vacuum gauge by measuring the degree of vacuum using the vacuum gauge and the main body vacuum gauge in each of a plurality of states in which the internal pressure of the reaction chamber is different.

[0052] In the radical reaction apparatus of paragraph 2, the degree of vacuum measured by the vacuum gauge possessed by the radical reaction apparatus can be made to coincide with the degree of vacuum measured by the main vacuum gauge possessed by an existing mass spectrometer, thereby making it possible to grasp the internal condition of the reaction chamber more accurately.

[0053] (Section 3) The radical reaction apparatus according to the third aspect of the present invention is the radical reaction apparatus according to the second aspect of the present invention, The vacuum gauge is provided at the same position as the main body vacuum gauge in a direction along the central axis of the ion flight path.

[0054] The space in which the reaction chamber is placed and the reaction chamber are provided with an inlet and an outlet for ions. Also, the reaction chamber is provided with an inlet for CID gas and an inlet for radicals. Therefore, the pressure may differ depending on the distance from these. In the radical reaction device according to paragraph 3, the vacuum gauge of the radical reaction device and the main vacuum gauge of the existing mass spectrometer are provided at the same position in the direction along the central axis of the flight path of the ions, i.e., at a position at the same degree of vacuum. Therefore, these vacuum gauges can be used to measure the degree of vacuum in spaces at the same degree of vacuum, and the vacuum gauge can be calibrated more accurately.

[0055] (Section 4) The radical reaction apparatus according to the fourth aspect of the present invention is the radical reaction apparatus according to the second or third aspect of the present invention, The plurality of states include a first state in which the reaction chamber is evacuated to a vacuum, and a second state in which a predetermined flow rate of CID gas is introduced into the first state.

[0056] In the radical reaction apparatus according to paragraph 4, the first state in which the reaction chamber is normally evacuated to a vacuum and no collision induced dissociation gas is introduced, allowing radicals to be introduced, and the second state used when dissociating precursor ions derived from sample components by collision induced dissociation, can be used as is when calibrating the vacuum gauge.

[0057] (Section 5) The radical reaction apparatus according to claim 5 is the radical reaction apparatus according to claim 4, The predetermined condition is to satisfy a criterion that is determined based on a measurement value of the vacuum gauge in the first state.

[0058] In the radical reaction apparatus according to paragraph 5, the predetermined standard can be simply and appropriately determined based on the measured value obtained during calibration of the vacuum gauge.

[0059] (Section 6) The radical reaction apparatus according to claim 6 is the radical reaction apparatus according to any one of claims 1 to 5, The radical generation control unit stops the operation of the radical generation unit when the degree of vacuum inside the reaction cell measured by the vacuum gauge no longer satisfies a predetermined condition while the radical generation unit is operating to analyze a sample.

[0060] In the radical reaction apparatus of paragraph 6, even if the degree of vacuum inside the reaction chamber decreases due to a malfunction of the vacuum pump during sample measurement, the operation of the radical generation section is stopped, thereby reducing the possibility of undesired product ions being generated, mass shifts occurring due to the desired ion cooling state not being obtained, or unintended discharges occurring due to radicals being introduced into the reaction cell in an insufficient degree of vacuum. [Explanation of symbols]

[0061] 1...Mass spectrometer 10…Ionization chamber 100…Vacuum chamber 101…ESI probe 102...solvent removal tube 11…First intermediate vacuum chamber 111…Ion Guide 112…Skimmer 12...Second intermediate vacuum chamber 121…Ion lens 13…Third intermediate vacuum chamber 131…Ion lens 14…1st analysis room 141...Quadrupole mass filter 142…Collision cell 143...Multipole ion guide 144...Ion transport electrode 145...Vacuum gauge 15…Second analysis room 151...Ion transport electrode 152...Orthogonal acceleration section 153...Second acceleration section 154...Reflectron electrode 155…Ion detector 156…Flight tube 4...Radical reaction device 40... Radical generation section 41...Quartz tube 42…Reaction cell 421…Aperture 422...Connecting member 423...Vacuum gauge 424...Base material 43...Multipole ion guide 44…Mass flow controller No. 1 45…Hydrogen gas supply port 46…2nd mass flow controller 47…Water tank 48...Flow path switching valve 51…First turbomolecular pump 52…Second turbomolecular pump 53…Back pump 54…Exhaust line 55…CID gas supply source 56…Third mass flow controller 6...Second control section 61...Storage section 62…Proofreading Department 63... Radical production control section 64...Input section 65...Display section 7…Control and processing section 71...Storage section 72…Analysis Execution Department 73...Input section 74...Display section C…Ion optical axis

Claims

1. A radical reaction device used in place of a collision cell that dissociates ions generated from a sample in a mass spectrometer, comprising: A radical generator that generates a predetermined type of radical; a reaction cell having a radical inlet into which the radicals generated in the radical generation section are introduced; a vacuum gauge for measuring a degree of vacuum in a space in which the reaction cell is disposed or inside the reaction cell; a radical generation control unit that operates the radical generation unit when the degree of vacuum measured by the vacuum gauge satisfies a predetermined condition; A radical reaction apparatus comprising:

2. The mass spectrometer includes a body vacuum gauge that is attached to a space in which the collision cell is disposed or to an inside of the collision cell; moreover, The radical reaction apparatus of claim 1, wherein the vacuum gauge is calibrated against the main vacuum gauge by measuring the degree of vacuum using the vacuum gauge and the main vacuum gauge in each of a plurality of different pressure states inside the reaction chamber.

3. 3. The radical reaction apparatus according to claim 2, wherein the vacuum gauge is provided at the same position as the main body vacuum gauge in a direction along a central axis of the flight path of the ions.

4. 3. The radical reaction apparatus according to claim 2, wherein the plurality of states are a first state in which the reaction chamber is evacuated to a vacuum and a second state in which a predetermined flow rate of CID gas is introduced into the first state.

5. 2. The radical reaction device according to claim 1, wherein the predetermined condition is to satisfy a criterion determined based on a measurement value of the vacuum gauge in the first state.

6. The radical reaction apparatus according to claim 1, wherein the radical generation control unit stops operation of the radical generation unit when the degree of vacuum inside the reaction cell measured by the vacuum gauge no longer satisfies a predetermined condition while the radical generation unit is operating to analyze a sample.

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