Ion analyzer and ion analysis method

Abstract

To prevent contamination of a member such as an electrode due to a radical for radical induction dissociation without deteriorating an analysis efficiency.SOLUTION: An ion analyzer that analyzes an ion dissociated by an act of a radical, comprises: generation parts (21 and 210) that generate the radical from a material gas; gas supply parts (26 and 3) that supply, during an execution of an analysis, a mixed gas obtained by mixing a first gas that becomes a raw material of the radical having an oxidation ability or having the oxidation ability itself and a second gas that becomes a raw material of the radical having a reduction ability or having the reduction ability itself, at a predetermined ratio defined so that an efficiency of dissociation by the radical derived from the first gas is not lower than the efficiency in the case where the second gas is not mixed to the generation part as a material gas; and a reaction chamber (132) into which the radical generated by the generation part is introduced, and brings the radical into contact with an ion derived from a sample.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an ion analyzer and an ion analysis method for analyzing ions derived from a target component contained in a sample.

Background Art

[0002] In order to identify sample components such as polymer compounds contained in a sample or analyze their structures, ions having a specific m / z (mass-to-charge ratio) are selected from ions derived from the sample components, and various product ions generated by dissociating the ions are separated and detected according to m / z. A mass spectrometry method is widely used. Various methods are known as ion dissociation methods. As one of them, a radical-induced dissociation method (also called "radical attachment dissociation method", but referred to as "radical-induced dissociation method" in this specification) in which various radicals are attached to ions or reacted with ions to dissociate the ions is known.

[0003] For example, Patent Document 1 describes that radical-induced dissociation is caused by irradiating ions with hydroxyl (OH) radicals, oxygen radicals, nitrogen radicals, etc. generated by high-frequency discharge, and mass-analyzing the product ions generated thereby. Patent Document 2 also describes that it is possible to analyze the double bond position that determines the biological activity of lipids by MS / MS analysis using a radical-induced dissociation method using hydroxyl radicals and oxygen radicals.

[0004] On the one hand, Patent Document 3 describes an example of a radical generation device for generating radicals used in the above-described radical-induced dissociation method. This radical generation device has a quartz tube and a helical antenna configured by winding a strip-shaped conductor around the outer periphery thereof. A raw material gas such as water vapor is introduced into the quartz tube, and plasma is generated inside the quartz tube by supplying high-frequency (microwave) power to the helical antenna, and radicals are generated in the plasma. Further, a magnet that generates a strong magnetic field is disposed outside the quartz tube, and the density of the plasma in the quartz tube is increased and the generation of the plasma is stabilized by electron cyclotron resonance using this magnetic field. Since this radical generation device utilizes local inductive discharge and electron cyclotron resonance for the generation and maintenance of plasma, it is sometimes called an ECR-LICP (Electron Cyclotron Resonance - Localized Inductively Coupled Plasma) type.

[0005] As described above, in the radical-induced dissociation method, various radical species can be used, and it is desirable to selectively use radical species according to the purpose of analysis and the type of compound. In order to selectively use various radical species with a single mass spectrometer, it is only necessary to switch the type of raw material gas supplied to the radical generation device as described above. For example, in the mass spectrometer described in Patent Document 4, a configuration is adopted in which hydroxyl radicals, oxygen radicals, and hydrogen radicals can be selectively introduced into the collision cell by switching between water vapor and hydrogen gas as the raw material gas.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

Problems to be Solved by the Invention

[0007] In a mass spectrometer capable of performing MS / MS analysis using the above-described radical-induced dissociation (hereinafter referred to as "radical-induced MS / MS analysis"), in order to improve the analysis sensitivity, it is important to increase the efficiency of radical-induced dissociation. To increase the efficiency of radical-induced dissociation, it is important to introduce a large amount of radicals into the collision cell, efficiently contact the radicals with the precursor ions incident on the collision cell, and further collect the generated product ions without waste and send them to the subsequent stage. However, since hydroxyl radicals and oxygen radicals have oxidizing ability, they easily form metal oxides on the surfaces of metal members such as electrodes in the collision cell. When a metal oxide film is formed on the surface of an electrode or the like, an undesired charge-up occurs there, and the desired electric field cannot be formed, resulting in a problem that the behavior of ions cannot be appropriately controlled.

[0008] On the other hand, in the mass spectrometer described in Patent Document 4 above, by selecting water vapor as the source gas during the analysis, hydroxyl radicals and oxygen radicals are introduced into the collision cell to promote the radical-induced dissociation of sample-derived ions, while hydrogen gas is selected as the source gas during the maintenance of the apparatus to supply hydrogen radicals into the collision cell. Hydrogen radicals can be used to dissociate ions, but they also have a strong reducing action and serve to remove the metal oxides formed on the surfaces of metal members such as electrodes. Therefore, in the above conventional mass spectrometer, it can be expected to remove the metal oxide film formed on the surface of an electrode or the like during the maintenance of the apparatus and reduce the occurrence of undesired charge-up during the next analysis.

[0009] However, in a liquid chromatography mass spectrometer in which, for example, a liquid chromatograph is connected to the front stage of a mass spectrometer, it often takes a long time to analyze one sample, and as time elapses from the start of the analysis, contamination of members such as electrodes progresses and the analysis sensitivity may decrease. Further, once the contamination of the electrodes and the like becomes severe, there is also a problem that it takes a long time to remove the oxide even when hydrogen radicals are supplied during apparatus maintenance.

[0010] The present invention has been made to solve such problems, and its main object is to provide an ion analyzer and an ion analysis method capable of preventing or reducing contamination of members such as electrodes caused by radicals for radical-induced dissociation and improving the efficiency of radical-induced dissociation.

Means for Solving the Problems

[0011] One aspect of the ion analyzer according to the present invention is an ion analyzer that analyzes ions dissociated by the action of radicals, comprising: a generation unit that generates radicals from a source gas; a gas supply unit that, during the execution of analysis, supplies a mixed gas, which is obtained by mixing a first gas that serves as a source of radicals having oxidizing ability or itself has oxidizing ability and a second gas that serves as a source of radicals having reducing ability or itself has reducing ability, to the generation unit as the source gas at a predetermined ratio determined such that the dissociation efficiency by radicals derived from the first gas is not lower than that when the second gas is not mixed; a reaction chamber into which the radicals generated by the generation unit are introduced, and the radicals are brought into contact with ions derived from a sample to dissociate the ions; and is provided with.

[0012] Further, one aspect of the ion analysis method according to the present invention is an ion analysis method that uses an ion analyzer including a generation unit that generates radicals from a source gas and a reaction chamber into which the radicals generated by the generation unit are introduced and the radicals are brought into contact with ions derived from a sample to dissociate the ions, and analyzes the ions dissociated in the reaction chamber, comprising: During the execution of the analysis, a first gas that serves as a raw material for radicals having oxidizing ability or itself has oxidizing ability, and a second gas that serves as a raw material for radicals having reducing ability or itself has reducing ability are mixed at a predetermined ratio determined such that the dissociation efficiency by radicals derived from the first gas is not lower than that when the second gas is not mixed, and the mixed gas is supplied as a raw material gas to the generation unit.

Advantages of the Invention

[0013] In the ion analyzer and ion analysis method according to the above aspect of the present invention, a first gas that serves as a raw material for radicals having oxidizing ability, such as water vapor, and a second gas that serves as a raw material for radicals having reducing ability, such as hydrogen gas, are not alternative but mixed at a predetermined ratio and supplied to the generation unit. However, when the first gas and the second gas are mixed in this way to form a raw material gas, radicals generated from the second gas may combine or react with radicals generated from the first gas, resulting in a decrease in the amount of radicals derived from the first gas and a possible reduction in the efficiency of radical-induced dissociation. For example, when water vapor and hydrogen gas are mixed to form a mixed gas, hydrogen radicals derived from hydrogen gas may combine or react with hydroxyl radicals derived from water vapor, reducing the hydroxyl radicals contributing to radical-induced dissociation. Therefore, here, the mixing ratio of the second gas in the raw material gas is restricted so that the radicals derived from the second gas do not become excessive to the extent that the efficiency of radical-induced dissociation decreases compared to the case where the second gas is not mixed (the case of only the first gas). As a result, in the reaction chamber, ions derived from the sample are dissociated mainly by the action of radicals generated from the first gas, and at the same time, oxides formed on the surface of members such as electrodes arranged in the reaction chamber, for example, are effectively removed by the reducing action of radicals generated from the second gas.

[0014] According to the ion analyzer and the ion analysis method according to the above aspect of the present invention in this way, it is possible to prevent or reduce the contamination of members such as electrodes by radicals for radical-induced dissociation while performing the analysis. Thereby, it is possible to avoid a decrease in the efficiency of radical-induced dissociation during the analysis and maintain good analysis sensitivity.

Brief Description of the Drawings

[0015]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Embodiments for Carrying Out the Invention

[0016] An embodiment of the ion analyzer and the ion analysis method according to the present invention will be described with reference to the accompanying drawings. Hereinafter, a mass spectrometer will be described as an embodiment of the ion analyzer, but it is obvious from the following description that the present invention is not limited thereto, and an ion mobility analyzer or an ion mobility-mass spectrometer may also be used.

[0017] FIG. 1 is a schematic configuration diagram of the mass spectrometer of the present embodiment. This mass spectrometer is a quadrupole-time-of-flight (Q-TOF type) mass spectrometer equipped with an atmospheric pressure ion source.

[0018] As shown in FIG. 1, this mass spectrometer includes an ionization chamber 10 and a vacuum chamber 1. The inside of the ionization chamber 10 is in a substantially atmospheric pressure atmosphere. The inside of the vacuum chamber 1 is partitioned into a plurality (four chambers in this embodiment as an example), and in order from the side closer to the ionization chamber 10, there are a first intermediate vacuum chamber 11, a second intermediate vacuum chamber 12, a first analysis chamber 13, and a second analysis chamber 14. Each of these chambers is evacuated by a vacuum pump (rotary pump and / or turbo molecular pump) not shown, and exhibits a configuration of a multi-stage differential evacuation system in which the degree of vacuum increases in order from the ionization chamber 10 toward the second analysis chamber 14.

[0019] An electrospray ionization (ESI) probe 101 that charges and sprays a liquid sample (that is, electrospray) is provided in the ionization chamber 10, and the ionization chamber 10 and the first intermediate vacuum chamber 11 communicate with each other through a thin-diameter desolvation tube 102. 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. Ion guides 111 and 121 are respectively arranged in the first intermediate vacuum chamber 11 and the second intermediate vacuum chamber 12. In the first analysis chamber 13, along the ion optical axis C, there are arranged a quadrupole mass filter 131 that separates ions according to m / z, a collision cell 132 having a multipole ion guide 133 inside, and an ion transport electrode 134 for transporting ions. The quadrupole mass filter 131 and the multipole ion guide 133 are each composed of a plurality of rod electrodes, and the ion transport electrode 134 is composed of a plurality of ring-shaped electrodes arranged along the ion optical axis C.

[0020] An opening 1320 is formed in the wall surface of the collision cell 132, and a cylindrical tube connection member 1321 is provided so that one end surrounds the opening 1320. Inside the tube connection member 1321, a quartz tube 210 extending from the radical generation unit 2 is inserted, and the end of the quartz tube 210 protrudes into the collision cell 132 through the opening 1320. In the collision cell 132, as will be described later, ions are dissociated by radicals supplied from the radical generation unit 2. Although not shown here, in addition to the radical generation unit 2, a gas (typically argon gas) for causing collision-induced dissociation (CID) in the collision cell 132 can be supplied to the collision cell 132.

[0021] In the second analysis chamber 14, there are arranged an ion transport electrode 141 for transporting ions incident from the first analysis chamber 13, an orthogonal acceleration unit 142 including a set of electrodes arranged opposite to each other with the ion optical axis C interposed therebetween, a plurality of acceleration electrodes 143, a flight tube 144 forming a flight space inside, a reflectron electrode 145 forming a folded trajectory of ions in the flight space, and an ion detector 146 for detecting ions. The ion detector 146 is, for example, a multi-channel plate type detector. The detection signal by the ion detector 146 is input to the data processing unit 4. Although the description of signal lines is omitted except for a part, the control unit 3 controls a power supply for applying a voltage or the like to each unit in addition to the radical generation unit 2 and the data processing unit 4.

[0022] A typical MS / MS analysis operation in the mass spectrometer having the above configuration, which is performed under the control of the control unit 3, is as follows. The ESI probe 101 sprays the liquid sample into the ionization chamber 10 while charging the liquid sample, and ionizes the compound in the liquid sample. The generated ions are sent to the first intermediate vacuum chamber 11 through the desolvation tube 102. The ions incident on the first intermediate vacuum chamber 11 are sent to the first analysis chamber 13 through the ion guide 111, the small hole of the skimmer 112, and the ion guide 121, and are introduced into the quadrupole mass filter 131.

[0023] Among the various introduced ions, only the ions having a specific m / z value selectively pass through the quadrupole mass filter 131 and are introduced into the collision cell 132 as precursor ions. Radicals are introduced into the collision cell 132 from the radical generation unit 2 through the quartz tube 210, and the precursor ions react with these radicals and dissociate. The various product ions generated by the dissociation exit the collision cell 132 and are introduced into the orthogonal acceleration unit 142 through the ion transport electrodes 134 and 141.

[0024] The ions introduced into the orthogonal acceleration unit 142 along the ion optical axis C are ejected in a direction substantially orthogonal to the ion optical axis C at an appropriate timing. The ejected ions are accelerated by the acceleration electrode 143 and introduced into the flight space in the flight tube 144. The ions fly back by the electric field formed by the reflectron electrode 145 and finally reach the ion detector 146. The ion detector 146 outputs an ion intensity signal corresponding to the amount of ions reaching the detector 146 to the data processing unit 4. The flight time of the ions from the time they leave the orthogonal acceleration unit 142 until they reach the ion detector 146, that is, the flight time of the ions, depends on the m / z value of the ions. Therefore, the data processing unit 4 creates a flight time spectrum showing the relationship between the flight time and the ion intensity based on the ion intensity signals received as time elapses, and creates a mass spectrum by converting the flight time into an m / z value.

[0025] Next, the detailed configuration and operation of the radical generation unit 2 for generating radicals will be described. As shown in FIG. 1, the radical generation unit 2 includes a plasma generation unit 21. The plasma generation unit 21 generates plasma based on a source gas such as water vapor supplied from the source gas supply source 26, and supplies the radicals generated in the plasma to the collision cell 132. The microwave power supply 25 supplies microwave power for generating plasma to the plasma generation unit 21.

[0026] The raw material gas supply source 26 includes a steam supply pipe 260 provided with a first mass flow controller (MFC) 262, a hydrogen supply pipe 261 provided with a second MFC 263, a water storage section 264 connected to the inlet end of the steam supply pipe 260, and a hydrogen cylinder (or hydrogen generator) 265 connected to the inlet end of the hydrogen supply pipe 261. The other ends of the steam supply pipe 260 and the hydrogen supply pipe 261 are both connected to the quartz tube 210. The water storage section 264 is equipped with a heater (not shown) and can supply the steam generated by heating the stored water through the steam supply pipe 260.

[0027] Figure 2 is a longitudinal sectional view of the main part centered on the plasma generation section 21. The plasma generation section 21 includes a long quartz tube 210 extending in the vertical direction in FIG. 2, a helical antenna 211 which is a strip-shaped conductor spirally wound around the outer periphery of a part of the quartz tube 210, an outer conductor section 212 made of a conductor having a cylindrical opening coaxial with the quartz tube 210 and having an inner diameter slightly larger than the outer diameter of the quartz tube 210, a permanent magnet 213 embedded in the outer conductor section 212, a casing 214 for holding the outer conductor section 212, and a permanent magnet 215 arranged at the bottom of the casing 214. The casing 214 is provided with a microwave supply connector 216, an ultraviolet light source 217, and a photodetector 218. When deep ultraviolet light is irradiated from the ultraviolet light source 217 to the quartz tube 210, electrons are emitted from the wall surface of the quartz tube 210, and the lighting (ignition) of the plasma is induced by these electrons.

[0028] The quartz tube 210 is a raw material introduction tube through which the raw material gas is introduced from the raw material gas supply source 26, and a part of the inside of the tube serves as a generation unit that generates radicals and a flow path that introduces the radicals into the collision cell 132. The microwave supply connector 216 is a coaxial connector and is connected to the microwave power supply 25 via a coaxial cable. The conductive wire of the microwave supply connector 216 is connected to one end (the lower end in FIG. 2) of the helical antenna 211. Although not shown, the outer conductor portion 212 is grounded. A part of the helical antenna 211 and the outer conductor portion 212 are electrically connected via the resonator adjustment mechanism 220, and the helical antenna 211 is grounded at the connection position. A resonator for electron cyclotron resonance is constituted by the helical antenna 211, the outer conductor portion 212, the resonator adjustment mechanism 220, and the like. The resonator adjustment mechanism 220 is used for adjusting the resonator and is, for example, the one described in Patent Document 3.

[0029] This plasma generation unit 21 has a configuration called an ECR-LICP type that utilizes local inductively coupled discharge and electron cyclotron resonance for the generation and maintenance of plasma.

[0030] A substantially disk-shaped magnet holder 221 is attached to the bottom surface of the casing 214. The casing 214 and the magnet holder 221 function as a holding member 222 that holds the quartz tube 210. An opening through which the quartz tube 210 is inserted is formed at substantially the center of the magnet holder 221. As shown in FIG. 2, the plasma generation unit 21 is mounted on the outer surface of the vacuum chamber 1, and the quartz tube 210 held by the holding member 222 is inserted into the inside of the tube connection member 1321 that connects between the collision cell 132 and the vacuum chamber 1 and reaches inside the collision cell 132. Since the inside of the quartz tube 210 and the inside of the collision cell 132 communicate with each other, the inside of the quartz tube 210 is also in a vacuum state when no raw material gas is supplied to the quartz tube 210.

[0031] As described above, in the mass spectrometer of the present embodiment, while flowing the source gas from the source gas supply source 26 into the quartz tube 210, high-frequency discharge by the microwave power supplied from the microwave power supply 27 is generated in the quartz tube 210, thereby generating radicals derived from the source gas. Then, these radicals are introduced into the collision cell 132, and MS / MS analysis using the radical-induced dissociation method is performed. Here, as the source gas that becomes the source of the radicals generated in the radical generation unit 2, the user can appropriately select one from among three options: a mixed gas of water vapor / hydrogen gas, water vapor only, and hydrogen gas only.

[0032] When water vapor is used as the source gas, the radical generation unit 2 can generate hydroxyl radicals and oxygen radicals. On the other hand, when hydrogen gas is used as the source gas, the radical generation unit 2 can generate hydrogen radicals. As disclosed in Patent Document 2, hydroxyl radicals and oxygen radicals are particularly useful for analyzing the double bond positions that determine the biological activity of lipids.

[0033] Thus, hydroxyl radicals and oxygen radicals are radical species useful for radical-induced dissociation. However, due to their high oxidizing ability, they promote the oxidation of metal members such as the surface of the electrodes such as the multipole ion guide 133 disposed in the collision cell 132 and the inner wall surface of the collision cell 132. Most of the metal oxides formed by this oxidation are insulators, and when an insulating film is formed on the surface of the electrodes or the like, undesired charge-up occurs during analysis. When charge-up occurs, the electric field formed by the electrodes does not reach the intended state, and there is a risk that the passage efficiency of ions decreases. As described above, in the mass spectrometer described in Patent Document 4, during the execution of the maintenance mode when it is not in the analysis state, hydrogen radicals having reducing ability are introduced into the collision cell to remove the oxides formed on the electrode surface and the like. However, with such a method, it is not possible to prevent or reduce the contamination of the electrodes and the like during the execution of the analysis, and there is a risk that the efficiency of radical-induced dissociation decreases over time.

[0034] In contrast, in the mass spectrometer of this embodiment, during the execution of MS / MS analysis, hydrogen gas is flowed into the quartz tube 210 simultaneously with water vapor that serves as a source of radicals for radical-induced dissociation, and the reducing ability of hydrogen radicals (and hydrogen gas itself) generated from the hydrogen gas is used to remove oxides on the electrode surface and the like while performing MS / MS analysis.

[0035] Here, the results of experimentally confirming the ion intensity enhancement effect when flowing hydrogen gas into the quartz tube 210 simultaneously with water vapor will be described. FIG. 3 is an example of a total ion current chromatogram of the measured results of radical-induced MS / MS analysis when hydrogen gas is added starting from a state where only water vapor is used as the source gas (that is, the source gas is a mixed gas of water vapor / hydrogen). In this measurement, while continuously supplying the same sample (here, NaI is used) to the ESI probe 101, the total ion current obtained by MS / MS analysis is observed. Until about 1.39 min has elapsed from the start of the analysis, only water vapor is flowed as the source gas at a flow rate of 0.5 sccm, and when about 1.39 min has elapsed, hydrogen gas is added at a flow rate of 0.5 sccm while maintaining the flow rate of water vapor. That is, the mixing ratio of the gases at the time of adding hydrogen gas is 1:1.

[0036] From FIG. 3, it can be seen that when hydrogen gas is additionally introduced starting from a state where only water vapor is used as the source gas, the ion intensity increases rapidly and significantly. This is presumably because the oxides formed on the surface of the electrode are removed by the reducing action of hydrogen radicals generated from hydrogen gas, and the electric field formed by the multipole ion guide 133 and the like approaches the expected state, so the passing efficiency of ions, and thus the efficiency of radical-induced dissociation, is restored.

[0037] Figure 4 shows an example of the results of actually measuring the change in the ion intensity of a predetermined product ion generated by radical-induced dissociation when the flow rate of hydrogen gas added with respect to the flow rate of water vapor is changed. Since this product ion is an ion generated by radical-induced dissociation (difficult to generate by other dissociations such as collision-induced dissociation), it can be said that the higher the ion intensity of this product ion, the higher the efficiency of radical-induced dissociation. From the results of Figure 4, the following can be understood. · The change in ion intensity with respect to the change in the mixing ratio of hydrogen gas is large, and there is clearly an optimal value for the mixing ratio of water vapor and hydrogen gas from the perspective of ion intensity. · When the flow rate of hydrogen gas is approximately the same as the flow rate of water vapor (the mixing ratio is about 1:1), the ion intensity becomes the highest. That is, the efficiency of radical-induced dissociation is almost maximized. · Needless to say, when hydrogen gas is not flowed (the flow rate of hydrogen gas = 0), and also when the flow rate of hydrogen gas is too high, the ion intensity will decrease. In particular, in this example, when the ratio of the flow rate of hydrogen gas exceeds 2 - 2.1, the ion intensity becomes lower than the ion intensity when hydrogen gas is not flowed (the flow rate of hydrogen gas = 0) (the horizontal line indicated by the dashed-dotted line in Figure 4), and the addition of hydrogen gas has a reverse effect.

[0038] The above experimental results can be physically explained as follows. That is, when water vapor and hydrogen gas are flowed simultaneously, if the flow rate of hydrogen gas is small, the oxidation action by hydroxyl radicals and the like is stronger than the reduction action by hydrogen radicals, so the reduction effect cannot be obtained sufficiently and it is difficult to improve the ion intensity. On the other hand, if the flow rate of hydrogen gas is too high with respect to water vapor, the opportunity for contact between hydroxyl radicals and hydrogen radicals increases and their combination and reaction are likely to occur. As a result, the hydroxyl radicals contributing to the target radical-induced dissociation decrease, the efficiency of radical-induced dissociation decreases, and the ion intensity decreases.

[0039] From the above, it can be understood that it is necessary to set the mixing ratio of hydrogen gas to water vapor to a predetermined value or less in order to satisfy the minimum condition of exceeding the ionic strength when hydrogen gas is not mixed (the raw material gas is only water vapor). In the example of Fig. 4, the value of the mixing ratio is about 1:2 for water vapor:hydrogen gas. However, this is the minimum condition, and more generally, the flow rate of hydrogen gas is such that an amount of hydrogen radicals sufficient for its reducing ability to be fully exerted is generated, and at the same time, it is desirable that an excessive amount of hydrogen radicals that would cause active binding and reaction with hydroxyl radicals is not generated. That is, it is desirable that the mixing ratio of water vapor and hydrogen gas is in a moderately balanced state. According to the measured example shown in Fig. 4, the optimal mixing ratio of water vapor and hydrogen gas is about 1:1.

[0040] Also, the ionic strength can be obtained at about 80% or more of its maximum value when the ratio of the flow rate of hydrogen gas is in the range of about 0.7 to 1.4 with respect to the flow rate of water vapor. Furthermore, the ionic strength can be obtained at about 60% or more of the maximum value when the ratio of the flow rate of hydrogen gas is in the range of about 0.46 to 1.6 with respect to the flow rate of water vapor. Also, since it is presumed that the change in ionic strength from the state where no hydrogen gas is mixed to the state where the mixing ratio of water vapor and hydrogen gas is about 1:1 is almost monotonically increasing, it can be said that even a very small mixing ratio of hydrogen gas is effective in improving the radical-induced dissociation efficiency. Also, as will be described later, although these numerical ranges are assumed to depend on conditions such as the type of gas, appropriate values or ranges may be investigated in advance according to the conditions such as the gas to be used.

[0041] Next, a typical control procedure when performing radical-induced MS / MS analysis in the mass spectrometer of this embodiment will be described with reference to the flowchart shown in Fig. 5.

[0042] For example, when an analysis start is instructed by the user (step S1), the control unit 3 that has received this instruction first controls the first MFC 262 and the second MFC 263 so that water vapor and hydrogen gas flow at predetermined flow rates respectively. Thereby, a mixed gas of water vapor and hydrogen gas is supplied as a raw material gas from the raw material gas supply source 26 to the quartz tube 210 and flows into the collision cell 132 through the plasma generation unit 21 (step S2). The gas flow rate at this time can be, for example, water vapor: 0.5 sccm and hydrogen: 0.5 sccm assuming that the mixing ratio when the ion intensity becomes maximum is 1:1 as described above. Such an appropriate flow rate ratio (or flow rate value) in the case of mixing and flowing water vapor and hydrogen gas can be determined in advance by experiments or the like and stored in the memory inside the control unit 3. In that case, the control unit 3 may control the MFCs 262 and 263 based on the information read from the memory.

[0043] After that, the control unit 3 operates the microwave power supply 25 to turn on the plasma that is in the off state. In response to this, the microwave power supply 25 starts supplying a predetermined microwave power to the plasma generation unit 21 (step S3). The frequency of the microwave can be, for example, 2.5 GHz. Also, the control unit 3 operates the ultraviolet light source 217 to start emitting deep ultraviolet light for promoting the lighting of the plasma. When the microwave power is supplied into the quartz tube 210, the raw material gas supplied as described above is ionized and the plasma lights up.

[0044] The photodetector 218 detects light in a wavelength band including the wavelength of the light emitted from the plasma. The control unit 3 monitors the output signal from this photodetector 218 and can confirm that the plasma is in the lit state based on the signal value. If it can be confirmed that the plasma has lit, the control unit 3 applies a predetermined voltage to each electrode such as the quadrupole mass filter 131 through a power supply (not shown) and executes radical-induced MS / MS analysis (step S4). During the execution of this radical-induced MS / MS analysis, a mixed gas of water vapor and hydrogen gas continues to be supplied to the quartz tube 210 as the raw material gas, and both hydroxyl radicals made from water vapor and hydrogen radicals made from hydrogen gas are introduced into the collision cell 132. As a result, in the collision cell 132, ions (precursor ions) derived from the sample are radical-induced dissociated, and the contamination on the surface of the electrodes such as the multipole ion guide 133 is removed mainly by the reduction action of hydrogen radicals. For example, when the conditions for the end of analysis are satisfied such as when a predetermined analysis time ends (Yes in step S5), the control unit 3 ends the analysis operation.

[0045] At the end of the analysis, the control unit 3 controls the first MFC 262 to stop the supply of water vapor (step S6). On the other hand, since hydrogen gas continues to be supplied, only hydrogen radicals and hydrogen gas are introduced into the collision cell 132. Since hydroxyl radicals and oxygen radicals are no longer introduced into the collision cell 132, oxidation of the electrode surface and the like does not proceed thereafter, and the oxides on the electrode surface are satisfactorily removed by the reduction action of hydrogen radicals. When a predetermined time has elapsed since the supply of water vapor was stopped, the control unit 3 controls the second MFC 263 to also stop the supply of hydrogen gas (step S8). At the same time, the power supply from the microwave power supply 25 is also stopped (step S9). As a result, the introduction of radicals and gas into the collision cell 132 is completely stopped.

[0046] According to the processes of steps S6 to S9 described above, only hydrogen gas is supplied as the source gas into the quartz tube 210 for a while after the supply of water vapor is stopped. If the supply of water vapor and hydrogen gas is stopped simultaneously, there is a possibility that the oxide formed on the electrode surface immediately before the supply stop may remain without being sufficiently removed. Also, for a while after the supply of water vapor is stopped, particles having oxidizing ability such as hydroxyl radicals and oxygen radicals may remain in the collision cell 132, and there is also a possibility that oxidation of the electrode surface such as the multipole ion guide 133 may progress due to their action.

[0047] On the other hand, in the mass spectrometer of the present embodiment, since the timing of stopping the hydrogen gas is delayed from the timing of stopping the water vapor, even after the hydroxyl radicals and oxygen radicals are almost completely discharged from the collision cell 132, hydrogen radicals remain in the collision cell 132 for a certain period of time. Thereby, the hydrogen radicals can sufficiently reduce the oxides on the electrode surface and the like, and remove those oxides. In this way, in the mass spectrometer of the present embodiment, when the analysis is completed, it is possible to prevent the metal members such as the electrodes from remaining in an oxidized state.

[0048] Note that the control of the gas supply at the end of the analysis described above should be executed not only at the end of the analysis but also when the analysis is interrupted (temporarily stopped) or when switching from radical-induced dissociation to CID, that is, when radical-induced dissociation is temporarily stopped.

[0049] Also, in the above description, the supply of water vapor and hydrogen gas is stopped by controlling the flow rates by the MFCs 262 and 263, respectively, but the gas supply may be stopped by simply closing the on-off valves. Further, instead of shifting the timing of stopping the supply of water vapor and hydrogen gas by electrical control, the supply of water vapor gas may be stopped with a delay after the supply of water vapor to the plasma generation unit 21 is stopped by mechanical delay.

[0050] For example, in FIG. 1, in the hydrogen supply pipe 261, the portion on the downstream side of the second MFC 263 (the range between the connection point of the second MFC 263 and the quartz tube 210) is made sufficiently longer than the portion on the downstream side of the first MFC 262 in the water vapor supply pipe 260. Thus, even when the gas supply is simultaneously stopped by the MFCs 262 and 263, the water vapor in the source gas flowing through the quartz tube 210 into the plasma generation chamber 21 is first blocked, and then the hydrogen gas is blocked with a delay corresponding to the difference in the pipe lengths (only the hydrogen gas has been flowing until then).

[0051] In the mass spectrometer of the above-described embodiment, water vapor was used as the first gas that is the source of radicals for radical-induced dissociation, and hydrogen gas was used as the second gas having reducing ability. However, the types of the first gas and the second gas are not limited to this. The first gas should be capable of generating radicals useful for the intended radical-induced dissociation (causing dissociation to generate product ions to be observed), and the radicals should have oxidizing ability or the gas itself should have oxidizing ability. In addition to the water vapor described above, the first gas can be, for example, oxygen gas, ozone gas, or a gas containing a compound containing oxygen atoms (e.g., water). On the other hand, the second gas should be a gas that generates radicals having reducing ability or a gas that itself has reducing ability. As the second gas, in addition to the hydrogen gas described above, nitrogen gas, or a gas of a compound containing hydrogen atoms, nitrogen atoms, or oxygen atoms such as carbon monoxide can be used.

[0052] Since the degree of oxidizing ability and reducing ability varies depending on the type of gas, when the first gas and the second gas are mixed and supplied, the mixing ratio at which the ionic strength of the target product ion becomes maximum, that is, the optimal mixing ratio, and the range of mixing ratios at which a significant effect is obtained such that the ionic strength increases compared to the case of using only the first gas differ depending on the type of gas. That is, when using water vapor as the first gas and hydrogen gas as the second gas, the optimal mixing ratio is approximately 1:1, and a sufficient effect is obtained if the ratio of the flow rate of hydrogen gas is in the range of about 0.46 to 1.6 with respect to the flow rate of water vapor. Furthermore, as a minimum condition, it can be said that the ratio of the flow rate of hydrogen gas to the flow rate of water vapor should be greater than 0 and 2 or less. However, these numerical values can change when the types of the first gas and the second gas are different. Therefore, depending on the type of gas used as the raw material gas, it is preferable to experimentally investigate appropriate values or ranges, for example, and control the gas flow rate so that it reaches that value or falls within that range.

[0053] As an experiment for this purpose, as described in the above measurement example, an appropriate standard sample is electrostatically sprayed into the ionization chamber 10, and in that state, while changing the mixing ratio of water vapor (a gas having oxidizing ability) and hydrogen gas (a gas having reducing ability), the intensity of the peak of the target product ion having the same m / z value is observed to search for an appropriate mixing ratio. Of course, the experimental method is not limited to this, and it is only necessary to be able to find a mixing ratio at which the ionic strength of the target product ion is higher than when no gas having reducing ability is mixed. Also, such an experiment is usually carried out by the manufacturer of the device, and it is only necessary to store the information on the flow rate value and flow rate ratio determined based on the experimental results in the memory as control information. However, the user side may also be provided with a function to perform a similar or equivalent experiment and set or change the flow rate ratio and flow rate value based on the results.

[0054] In addition, the appropriate mixing ratio of the first gas and the second gas can vary depending not only on the types of the gases, but also on factors other than the gases, such as the gas flow rate itself, and the structure and size of the collision cell 132. Therefore, for example, it is preferable to examine appropriate values and ranges for each model of the mass spectrometer, depending not only on the types and flow rates of the gases.

[0055] Also, the above-described embodiment is an example in which the ion analyzer according to the present invention is applied to a Q-TOF type mass spectrometer, but it is obvious that the present invention is not limited to the Q-TOF type. Specifically, the present invention can also be applied to other types of mass spectrometers that dissociate ions for mass spectrometry, such as triple quadrupole type mass spectrometers, ion trap type mass spectrometers, and ion trap time-of-flight type mass spectrometers.

[0056] In addition, the present invention can be applied to an apparatus that dissociates ions using radicals generated in a plasma and analyzes product ions generated by the dissociation. Specifically, for example, the present invention can also be applied to an ion mobility analyzer that separates and detects ions according to their ion mobility, and an ion mobility-mass spectrometer that separates ions using both ion mobility and m / z.

[0057] Also, the configuration of the mass spectrometer described above, particularly the configuration of the radical generation unit 2 that generates radicals, is merely an example, and it is natural that it can be appropriately modified as long as it can generate radicals by plasma. In addition, such radicals generally include hydroxyl radicals, hydrogen radicals, oxygen radicals, nitrogen radicals, etc. that are used in radical-induced dissociation methods, as well as various molecules and atoms in an excited state or a metastable state that have been given energy.

[0058] Also, the above-described embodiment and various modified examples described above are merely examples of the present invention, and it is obvious that modifications, additions, etc. can be appropriately made within the scope of the gist of the present invention and still be included in the scope of the claims of this application.

[0059] [Various aspects] Those skilled in the art will understand that the above-exemplified embodiments are specific examples of the following aspects.

[0060] (Item 1) One aspect of an ion analyzer according to the invention is an ion analyzer that analyzes ions dissociated by the action of radicals, comprising: a generation unit that generates radicals from a source gas; during the execution of analysis, a first gas that serves as a source of radicals having oxidizing ability or itself has oxidizing ability, and a second gas that serves as a source of radicals having reducing ability or itself has reducing ability, are mixed at a predetermined ratio determined such that the dissociation efficiency by radicals derived from the first gas is not less than that in the case where the second gas is not mixed, and the mixed gas is supplied as the source gas to the generation unit; a reaction chamber into which the radicals generated by the generation unit are introduced, and the radicals are brought into contact with ions derived from a sample to dissociate the ions; and is provided with.

[0061] (Item 8) One aspect of an ion analysis method according to the invention is an ion analysis method that uses an ion analyzer comprising a generation unit that generates radicals from a source gas and a reaction chamber into which the radicals generated by the generation unit are introduced, and the radicals are brought into contact with ions derived from a sample to dissociate the ions, and analyzes the ions dissociated in the reaction chamber, comprising: during the execution of analysis, a first gas that serves as a source of radicals having oxidizing ability or itself has oxidizing ability, and a second gas that serves as a source of radicals having reducing ability or itself has reducing ability, are mixed at a predetermined ratio determined such that the dissociation efficiency by radicals derived from the first gas is not less than that in the case where the second gas is not mixed, and the mixed gas is supplied as the source gas to the generation unit.

[0062] In the ion analyzer according to claim 1 and the ion analysis method according to claim 8, in the reaction chamber, in parallel with the dissociation of sample-derived ions mainly by the action of radicals generated from the first gas, the oxide formed on the surface of members such as electrodes is removed by the reduction action of radicals generated from the second gas or the second gas itself. Therefore, according to the ion analyzer according to claim 1 and the ion analysis method according to claim 7, it is possible to prevent or reduce the contamination of members such as electrodes by radicals for radical-induced dissociation while performing the analysis. Thereby, it is possible to avoid a decrease in the efficiency of radical-induced dissociation during the analysis and maintain good analysis sensitivity.

[0063] (Item 2, Item 9) In the ion analyzer according to claim 1 and the ion analysis method according to claim 8, the predetermined ratio can be such that the flow rate of hydrogen gas is greater than 0 and less than or equal to 2 with respect to a flow rate of water vapor of 1.

[0064] (Item 3, Item 10) In the ion analyzer according to claim 2 and the ion analysis method according to claim 9, the predetermined ratio can be such that the flow rate of hydrogen gas is in the range of 0.4 to 1.6.

[0065] (Item 4, Item 11) In the ion analyzer according to claim 3 and the ion analysis method according to claim 10, the predetermined ratio can be such that the flow rate of hydrogen gas is in the range of 0.7 to 1.4.

[0066] According to the ion analyzer described in claim 2 and the ion analysis method described in claim 9, it is possible to avoid a situation where the radicals derived from the first gas are reduced due to the combination or reaction with the radicals derived from the second gas because the amount of the second gas is too large, resulting in a decrease in ion intensity. Thereby, while effectively removing the oxide formed on the electrode surface or the like, it is possible to achieve high analysis sensitivity in radical-induced MS / MS analysis. Further, according to the ion analyzer described in claim 3 and the ion analysis method described in claim 10, it is possible to avoid a situation where the reduction effect by the second gas itself or the radicals derived from the second gas cannot be sufficiently obtained because the amount of the second gas is too small, and it is difficult for the ion intensity to increase, and high analysis sensitivity in radical-induced MS / MS analysis can be achieved. Furthermore, according to the ion analyzer described in claim 4 and the ion analysis method described in claim 11, even higher analysis sensitivity can be achieved.

[0067] (Item 5, Item 12) In the ion analyzer according to any one of Items 1 to 4 and the ion analysis method according to any one of Items 8 to 11, the first gas can be water vapor.

[0068] (Item 6, Item 13) Also, in the ion analyzer according to any one of Items 1 to 5 and the ion analysis method according to any one of Items 8 to 12, the second gas can be hydrogen gas.

[0069] According to the ion analyzer described in Item 5 or Item 6 and the ion analysis method described in Item 12 or Item 13, it is possible to accurately remove the contamination of the electrode while collecting the desired data by radical-induced MS / MS analysis.

[0070] (Item 7) In the ion analyzer according to any one of Items 1 to 6, the gas supply unit can be configured to continue supplying only the second gas for a predetermined time after stopping the supply of the first gas to the generation unit at the end of the analysis.

[0071] (Item 14) Further, in the ion analysis method according to any one of Items 8 to 13, after stopping the supply of the first gas to the generation unit at the end of the analysis, only the second gas may be continuously supplied for a predetermined time.

[0072] According to the ion analyzer described in Item 7 and the ion analysis method described in Item 14, even after the first gas and radicals derived from the first gas are almost completely discharged from the reaction chamber, radicals having a reducing ability derived from the second gas or the second gas itself having a reducing ability temporarily remain in the reaction chamber. Thereby, the second gas or radicals derived from the second gas can sufficiently reduce oxides on the electrode surface or the like and remove those oxides. In this way, the next analysis can be executed in a state where the oxides on the electrode surface or the like are sufficiently removed.

Explanation of Signs

[0073] 1…Vacuum chamber 10…Ionization chamber 101…ESI probe 102…Desolvation tube 11…First intermediate vacuum chamber 111, 121…Ion guide 112…Skimmer 12…Second intermediate vacuum chamber 13…First analysis chamber 131…Quadrupole mass filter 132…Collision cell 1320…Opening 1321…Tube connection member 133…Multipole ion guide 134, 141…Ion transport electrode 14…Second analysis chamber 142…Orthogonal acceleration section 143…Acceleration electrode 144…Flight tube 145…Reflectron electrode 146…Ion detector 2…Radical generation unit 21…Plasma generation unit 210…Quartz tube 211…Helical antenna 212… Outer conductor part 213, 215… Permanent magnets 214… Casing 216… Microwave supply connector 217… Ultraviolet light source 218… Photodetector 220… Resonator adjustment mechanism 221… Magnet holder 222… Holding member 25… Microwave power supply 26… Raw material gas supply source 260… Steam supply pipe 261… Hydrogen supply pipe 262, 263… Mass flow controller (MFC) 264… Water storage part 265… Hydrogen cylinder 3… Control unit 4… Data processing unit C… Ion optical axis

Claims

1. An ion analyzer for analyzing ions dissociated by the action of radicals, comprising: a generation unit that generates radicals from a source gas; during the execution of analysis, a first gas that serves as a source of radicals having oxidizing ability or itself has oxidizing ability, and a second gas that serves as a source of radicals having reducing ability or itself has reducing ability, are mixed at a predetermined ratio determined such that the dissociation efficiency by the radicals derived from the first gas is not less than that when the second gas is not mixed, and the mixed gas is supplied as the source gas to the generation unit; during the execution of analysis, a gas supply unit that supplies, as the source gas, a mixed gas in which a first gas serving as a source of radicals and a second gas that is a gas having reducing ability are mixed at a predetermined ratio, to the generation unit; a reaction chamber into which the radicals generated by the generation unit are introduced, and the radicals are brought into contact with ions derived from a sample to dissociate the ions; An ion analyzer comprising the above.

2. The ion analyzer according to claim 1, wherein the predetermined ratio is such that the flow rate of hydrogen gas is greater than 0 and not more than 2 with respect to a flow rate of water vapor of 1.

3. The ion analyzer according to claim 2, wherein the predetermined ratio is in the range of 0.4 to 1.6 for the flow rate of hydrogen gas.

4. The ion analyzer according to claim 3, wherein the predetermined ratio is in the range of 0.7 to 1.4 for the flow rate of hydrogen gas.

5. The ion analyzer according to claim 1, wherein the first gas is water vapor.

6. The ion analyzer according to claim 5, wherein the second gas is hydrogen gas.

7. The ion analyzer according to claim 1, wherein the gas supply unit, at the end of analysis, after stopping the supply of the first gas to the generation unit, continues to supply only the second gas for a predetermined time.

8. An ion analysis method for analyzing ions dissociated in the reaction chamber, using an ion analyzer comprising a generation unit that generates radicals from a source gas and a reaction chamber into which the radicals generated by the generation unit are introduced and the radicals are brought into contact with ions derived from a sample to dissociate the ions. During the execution of the analysis, a first gas that serves as a raw material for radicals having oxidizing ability or itself has oxidizing ability, and a second gas that serves as a raw material for radicals having reducing ability or itself has reducing ability are mixed at a predetermined ratio determined such that the dissociation efficiency by radicals derived from the first gas is not lower than that in the case where the second gas is not mixed. The mixed gas is supplied to the generation unit as a raw material gas. An ion analysis method.

9. The ion analysis method according to claim 8, wherein the predetermined ratio is such that the flow rate of hydrogen gas is greater than 0 and not more than 2 with respect to the flow rate of water vapor being 1.

10. The ion analysis method according to claim 9, wherein the predetermined ratio is in the range of 0.4 to 1.6 for the flow rate of hydrogen gas.

11. The ion analysis method according to claim 10, wherein the predetermined ratio is in the range of 0.7 to 1.4 for the flow rate of hydrogen gas.

12. The ion analysis method according to claim 8, wherein the first gas is water vapor.

13. The ion analysis method according to claim 12, wherein the second gas is hydrogen gas.

14. The ion analysis method according to claim 8, wherein at the end of the analysis, after stopping the supply of the first gas to the generation unit, only the second gas is continuously supplied for a predetermined time.

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