Ion Analyzer

Abstract

An ion analysis device (1) for generating product ions from precursor ions derived from sample components and analyzing the product ions comprises: a reaction chamber (132) into which the precursor ions are introduced; a radical emitter (134) disposed in the reaction chamber or in a space connected to the reaction chamber, wherein at least a portion of the surface of the radical emitter (134) is oxidized or nitrided and the radical emitter is composed of a specified type of metal; a heating unit (20) for heating the radical emitter to a specified temperature; and a separation and detection unit (135, 136) for separating and detecting the product ions generated from the precursor ions by the reaction between the precursor ions and radicals emitted from the radical emitter heated to the specified temperature, based on at least one of a mass-to-charge ratio and an ion mobility.

Description

Technical Field

[0001] The present invention relates to an ion analysis device that generates product ions by irradiating ions derived from sample molecules with radicals to dissociate the ions and analyzes the product ions. Background Art

[0002] When performing structural analysis of proteins or peptides as polymer compounds, it is effective to cleave the protein or peptide at a specific site and estimate the local structure of the protein or peptide based on ions generated by the cleavage.

[0003] Patent Document 1 describes an ion analyzer that generates product ions by irradiating precursor ions derived from protein or peptide sample molecules with free radicals and then analyzes the product ions. In this ion analyzer, a raw material gas is supplied to a vacuum-evacuated free radical generation chamber, and the raw material gas is simultaneously converted into plasma by high-frequency discharge to generate free radicals. The free radicals generated in the free radical generation chamber are then introduced into an ion trap that has captured the precursor ions derived from the sample component. The reaction between the precursor ions and the free radicals causes the precursor ions to dissociate, generating product ions. Patent Document 1 describes the ability to generate α and γ ions from peptide-derived ions using oxygen free radicals, generated using water vapor or air as the raw material gas. It also describes the ability to generate α, β, X, and γ ions from peptide-derived ions using nitrogen free radicals, generated using nitrogen as the raw material gas.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: International Publication No. 2018 / 186286

[0007] Patent Document 2: International Publication No. 2019 / 155725

[0008] Non-patent literature

[0009] Non-patent document 1: Shuro Hara, "Thermal decomposition of metal acid compounds and the release of atomic acid elements", Japan Science Magazine, Vol. 82, No. 2 (1961), p. 152-155 Summary of the Invention

[0010] Problems to be solved by the invention

[0011] The ion analyzer disclosed in Patent Document 1 generates plasma and free radicals from the raw gas by supplying high-output high-frequency power, such as 50W. While the mass spectrometer includes a high-frequency power supply for supplying high-frequency power to the electrodes that comprise the ion guide and mass separation section, the output of the high-frequency power supplied to these electrodes is only a few watts. Therefore, the ion analyzer disclosed in Patent Document 1 requires the addition of a high-output high-frequency power supply to generate free radicals. High-frequency power supplies with outputs of several tens of watts or more are expensive, and thus, the addition of such a power supply increases the cost of the ion analyzer.

[0012] The problem to be solved by the present invention is to provide an ion analysis device capable of generating oxygen radicals or nitrogen radicals for fragmentation of precursor ions at a lower cost than conventional methods.

[0013] Solutions for solving problems

[0014] The ion analysis apparatus according to the present invention, which has been developed to solve the above-mentioned problems, generates product ions from precursor ions derived from sample components and analyzes the product ions, and includes:

[0015] a reaction chamber into which the precursor ions are introduced;

[0016] a radical emitter disposed in the reaction chamber or in a space communicating with the reaction chamber, wherein at least a portion of the surface of the radical emitter is oxidized or nitrided and the radical emitter is composed of a predetermined type of metal;

[0017] a heating unit that heats the radical emitter to a predetermined temperature; and

[0018] The separation and detection unit separates and detects product ions generated from the precursor ions by the reaction between the precursor ions and radicals emitted from the radical emitter heated to the predetermined temperature, based on at least one of a mass-to-charge ratio and an ion mobility.

[0019] Effects of the Invention

[0020] In the ion analysis device of the present invention, oxygen radicals or nitrogen radicals are generated by heating a radical emitter composed of a specified metal, at least a portion of whose surface is oxidized or nitrided, to a specified temperature. The radical emitter can be, for example, a platinum wire coated with platinum oxide. In this case, the radical emitter can be heated to approximately 200°C by supplying a few watts of DC power, thereby generating oxidized radicals. Specifically, the specified temperature is the temperature at which oxygen radicals can be emitted from the radical emitter, and this temperature is predetermined based on prior knowledge or preliminary experiments. The radical emitter is located within a reaction chamber or a space connected to the reaction chamber, thereby supplying radicals to the reaction chamber and generating product ions from the precursor ions through a reaction between the precursor ions and the radicals. The generated product ions are separated and detected by a separation and detection unit based on at least one of mass-to-charge ratio and ion mobility. The ion analyzer according to the present invention does not require a power supply for supplying high-output high-frequency power as in conventional ion analyzers, and therefore can irradiate sample molecules with oxygen radicals or nitrogen radicals at low cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a diagram showing the main structure of a mass spectrometer as one embodiment of the ion analyzer according to the present invention.

[0022] Figure 2 This is a diagram showing the main structure of a mass spectrometer according to Modification 1 of the ion analyzer of the present invention.

[0023] Figure 3 This is a diagram showing the main structure of an oxygen radical generating / irradiating unit used in the mass spectrometer according to Modification 1.

[0024] Figure 4 This is a diagram showing the main structure of a mass spectrometer according to a second modification of the ion analyzer of the present invention.

[0025] Figure 5 This is a product ion spectrum obtained by measuring phospholipids using the mass spectrometer of Example 1. DETAILED DESCRIPTION

[0026] An embodiment of an ion analyzer according to the present invention will be described below with reference to the accompanying drawings. The ion analyzer of this embodiment is a mass spectrometer 1 that separates and detects product ions generated by fragmenting precursor ions derived from sample molecules based on their mass-to-charge ratios.

[0027] Figure 1 1 is a schematic structural diagram of a mass spectrometer 1 according to this embodiment. The mass spectrometer 1 is broadly divided into a mass spectrometer main body 2 and a control / processing unit 5 .

[0028] The mass spectrometer main body 2 is a so-called triple quadrupole mass spectrometer. It has a multi-stage differential exhaust system structure, which includes a first intermediate vacuum chamber 11 and a second intermediate vacuum chamber 12, each with a gradually increased vacuum level, between an ionization chamber 10, which is at approximately atmospheric pressure, and a high-vacuum analysis chamber 13, which is evacuated by a vacuum pump (not shown). The ionization chamber 10 and the first intermediate vacuum chamber 11 are connected via a desolvation tube 102. Furthermore, the first intermediate vacuum chamber 11 and the second intermediate vacuum chamber 12 are connected via a small hole formed in the top of a skimmer 112.

[0029] An ESI probe 101 is provided in the ionization chamber 10 . In order to converge ions and transport them to the subsequent stage, an ion lens 111 is provided in the first intermediate vacuum chamber 11 , and an ion guide 121 is provided in the second intermediate vacuum chamber 12 .

[0030] The analysis chamber 13 is provided with a front-stage quadrupole mass filter 131, a collision chamber 132, a rear-stage quadrupole mass filter 135 and an ion detector 136. A quadrupole ion guide 133 is arranged inside the collision chamber 132, and a metal wire 134 is arranged at a position closer to the wall than the quadrupole ion guide 133. The surface of the quadrupole ion guide 133 of the present embodiment is covered with gold. In addition, the metal wire 134 of the present embodiment is composed of platinum whose surface is covered with an oxide (platinum oxide). Covering the surface of the metal wire 134 can be performed, for example, by placing a platinum wire in an oxygen plasma generated by high-frequency discharge in a vacuum chamber independent of the mass spectrometry analysis device 1 in advance. In addition, in Figure 1 Although only one metal wire 134 is shown, multiple metal wires 134 may be provided. In either case, metal wire 134 is preferably positioned away from the central axis of the ion flight path (ion optical axis C) (e.g., further outward from the interior of quadrupole ion guide 133). This prevents ions from being lost due to collisions with metal wire 134. Here, a gold-coated ion guide is used as quadrupole ion guide 133, but a platinum-coated ion guide may also be used.

[0031] In addition to having a main rod for mass separation of ions by applying appropriate DC voltage and / or high-frequency voltage from a power supply not shown in the figure, the front-stage quadrupole mass filter 131 and the rear-stage quadrupole mass filter 135 also have a front rod and a rear rod for adjusting the electric field on the front-stage side and the rear-stage side of the main rod.

[0032] The metal wire 134 is connected to the first DC power supply 20. In addition, the quadrupole ion guide 133 is connected to the second DC power supply 30. The second DC power supply 30 is used for a purpose different from the power supply (not shown) that applies a DC voltage and / or a high-frequency voltage for selecting the mass-to-charge ratio of ions passing through the quadrupole ion guide 133. In this embodiment, the first DC power supply 20 and the second DC power supply 30 are configured independently of the power supply usually provided in the mass spectrometer, but they can also be combined into one power supply having multiple output systems. In addition, in Figure 1 In FIG. 1 , the second DC power supply 30 is connected to only one of the electrodes constituting the quadrupole ion guide 133 , but is actually connected to all the electrodes.

[0033] The collision chamber 132 is connected to the oxygen supply unit 4. The oxygen supply unit 4 includes an oxygen tank 41, an oxygen introduction flow path 42 for introducing oxygen from the oxygen tank 41 into the collision chamber 132, and a valve 43 for opening and closing the oxygen introduction flow path. Figure 1 Although not shown, a triple quadrupole mass spectrometer generally includes a unit for introducing a collision gas into the collision cell 132. Therefore, the oxygen supply unit 4 of this embodiment can be configured to supply oxygen to the collision cell 132 via such a collision gas introduction flow path.

[0034] The control / processing unit 5 controls the operation of the mass spectrometer main body 2 and stores and analyzes data obtained by the ion detector 136 of the mass spectrometer main body 2. The control / processing unit 5 is a typical personal computer, and its storage unit 51 stores method files describing measurement conditions and a compound database. Furthermore, the control / processing unit 5 includes an analysis control unit 52, an analytical processing unit 53, and an oxidation reaction control unit 54 as functional blocks. These functional blocks are implemented by executing predetermined programs pre-installed in the personal computer. Furthermore, the control / processing unit 5 is connected to an input unit 55 and a display unit 56.

[0035] Next, the operation of the mass spectrometer 1 of this embodiment will be described. When measuring sample components, the analysis control unit 52 controls the operation of each component, performing the following measurement operations. The analysis control unit 52 controls the operation of each component in accordance with the analysis conditions described in the method file stored in the storage unit 51.

[0036] First, the interiors of the first intermediate vacuum chamber 11, the second intermediate vacuum chamber 12, and the analysis chamber 13 of the mass spectrometer main body 2 are evacuated to a predetermined vacuum level using a vacuum pump. Next, a DC current is supplied from the second DC power supply 30 to the quadrupole ion guide 133, heating it to a predetermined temperature (e.g., 100°C). Furthermore, a DC current is supplied from the first DC power supply 20 to the metal filament 134, heating it to a predetermined temperature (e.g., 200°C). This causes platinum oxide to decompose on the surface of the metal filament 134, generating oxygen radicals. Heating the quadrupole ion guide 133 is not a required condition, but in many cases, a high-precision electric field is required in the collision cell 132 to control ion behavior. Therefore, it is preferable to heat the quadrupole ion guide 133 during measurement, as described above, to prevent oxide formation on the electrode surfaces. Furthermore, by pre-coating the surface of the quadrupole ion guide 133 with a precious metal such as gold or platinum, as in this embodiment, oxide formation can be prevented.

[0037] Next (or in parallel with the generation of free radicals), a sample is introduced into the ESI probe 101 to generate ions. This can be done by directly injecting the sample into the ESI probe 101, or by injecting the various components contained in the sample into a liquid chromatograph and sending the resulting eluate, after separation using a chromatographic column, to the ESI probe 101. The ions generated from the sample components within the ionization chamber 10 are drawn into the first intermediate vacuum chamber 11 due to the pressure difference between the ionization chamber 10 and the first intermediate vacuum chamber 11, and are focused onto the ion optical axis C by the ion lens 111. The ions focused onto the ion optical axis C are then drawn into the second intermediate vacuum chamber 12 due to the pressure difference between the first intermediate vacuum chamber 11 and the second intermediate vacuum chamber 12, and are further focused by the ion guide 121. Thereafter, in the analysis chamber 13, ions with a predetermined mass-to-charge ratio are filtered as precursor ions by the pre-quadrupole mass filter 131 and enter the collision chamber 132.

[0038] In the collision cell 132, oxygen free radicals attach to precursor ions derived from sample components, causing unpaired electron-induced fragmentation within the precursor ions to generate product ions. During this process, the quadrupole ion guide 133 is heated by the supply of direct current, thereby suppressing surface oxidation caused by the attachment of oxygen free radicals. The product ions generated by the fragmentation of the precursor ions are ejected from the collision cell 132, undergo mass separation by the post-quadrupole mass filter 135, and then are incident on the ion detector 136 for detection. The detection signals from the ion detector 136 are sequentially transmitted to the control / processing unit 5 and stored in the storage unit 51.

[0039] The analysis processing unit 53 generates a product ion spectrum based on the detection signal and displays the product ion spectrum on the display unit 56. The analysis processing unit 53 performs predetermined data processing based on the information (mass information and intensity) obtained from the product ion spectrum to estimate the structure of the sample component. For example, if the sample component is a phospholipid, the structure of the sample component is estimated based on information such as the difference between the mass of the product ion corresponding to the mass peak appearing in the product ion spectrum (a mass peak with an intensity that can be clearly distinguished from noise) and the mass of the head group included in the compound database stored in the storage unit 51.

[0040] As measurements are repeated in which oxygen radicals are released from the metal wire 134 to fragment precursor ions derived from the sample component, oxides gradually disappear from the surface of the metal wire 134, making it difficult to release oxygen radicals. Therefore, after measurements are performed for a predetermined period of time, a treatment is performed to oxidize the surface of the metal wire 134 under the control of the oxidation reaction control unit 54.

[0041] The oxidation reaction control unit 54 supplies oxygen from the oxygen tank 41 of the oxygen supply unit 4 via the oxygen inlet flow path 42 into the collision cell 132. Next, a DC voltage of a predetermined magnitude is applied from the second DC power supply 30 to the quadrupole ion guide 133. The walls of the collision cell 132 are often grounded, generating a DC discharge between the walls and the quadrupole ion guide 133. This generates oxygen free radicals from the oxygen within the collision cell 132. These generated oxygen free radicals adhere to the surface of the metal wire 134, forming oxides thereon. This replenishes the oxides on the surface of the metal wire 134 during measurement.

[0042] Thus, in the mass spectrometer 1 of this embodiment, oxygen free radicals are generated by heating a metal wire 134, whose surface is made of platinum oxide, to a predetermined temperature. Since the metal wire 134 is disposed within the collision cell 132, free radicals are supplied into the collision cell 132, and product ions are generated from the precursor ions through reactions between the free radicals and the precursor ions. Unlike conventional ion analyzers, the mass spectrometer 1 of this embodiment does not require a power supply that supplies high-output (e.g., tens of watts) high-frequency power. Instead, a low-output (e.g., a few watts) high-frequency power supply is sufficient. Therefore, a low-cost and compact power supply can be used to generate oxygen free radicals. Furthermore, since the oxygen free radicals are generated within the collision cell 132, where the precursor ions are introduced, there is no need to transport the oxygen free radicals, allowing the generated oxygen free radicals to be efficiently used in the fragmentation reaction of the precursor ions. Furthermore, in the mass spectrometer 1 of this embodiment, by generating oxygen free radicals from oxygen gas during non-measurement periods and attaching these free radicals to the metal wire 134, oxygen free radicals can be repeatedly generated from the metal wire 134.

[0043] In the above embodiment, oxygen radicals are generated from oxygen by generating a DC discharge in the collision cell 132. However, oxygen radicals may be generated by a high-frequency discharge instead of a DC discharge. Alternatively, when measurements are not being performed for a long period of time, the surface of the metal wire 134 may be gradually oxidized without generating a discharge by simply supplying oxygen into the collision cell 132.

[0044] The above embodiment is merely an example and can be modified as appropriate according to the spirit of the present invention. In the above embodiment, oxygen radicals are generated from oxygen in the collision cell 132 during non-measurement to oxidize the surface of the metal wire 134. However, oxygen radicals can also be supplied from outside the collision cell 132.

[0045] Figure 2 This is a diagram showing the main structure of a mass spectrometer main body 202 of a mass spectrometer 200 that supplies oxygen radicals from outside the collision cell 132 according to Modification 1. Components identical to those in the above-described embodiment are denoted by the same reference numerals, and their descriptions are omitted.

[0046] The mass spectrometer 200 according to the first modification is characterized in that it includes an oxygen radical generating / irradiating unit 6 . Figure 3 , a schematic structure of the oxygen radical generating / irradiating unit 6 is shown in FIG. The oxygen radical generating / irradiating unit 6 includes a nozzle 64 having a radical generating chamber 61 formed therein; a vacuum pump 67 for exhausting the radical generating chamber 61; a high-frequency power supply 63 for supplying microwaves for generating a vacuum discharge in the radical generating chamber 61; an oxygen tank 66 for supplying oxygen into the radical generating chamber 61; and a valve 661 for opening and closing the flow path of the oxygen tank 66.

[0047] The nozzle 64 includes a ground electrode 641 forming an outer periphery and a torch 642 located inside the ground electrode 641. The interior of the torch 642 forms a free radical generation chamber 61. The torch 642 can be made of, for example, Pyrex (registered trademark) glass. Inside the free radical generation chamber 61, a needle electrode 643 connected to a high-frequency power supply 63 via a connector 644 extends along the longitudinal direction of the free radical generation chamber 61.

[0048] The outlet end of the nozzle 64 is connected to a transport tube 68 for transporting radicals generated in the radical generation chamber 61 to the collision chamber 132. The transport tube 68 is an insulating tube, and a quartz tube, for example, can be used.

[0049] Multiple heads 681 are provided in the portion of the transport tube 68 disposed along the wall of the collision chamber 132 near the wire 134. Each head 681 is provided with an inclined conical irradiation port, which irradiates radicals in a direction intersecting the central axis of the ion flight direction (ion beam axis C). This allows the entire wire 134 to be uniformly irradiated with oxygen radicals.

[0050] In the mass spectrometry device 200 of modification example 1, oxygen free radicals are generated by high-frequency discharge in the same manner as in the mass spectrometry device described in patent document 1. However, in the mass spectrometry device 200 of modification example 1, it is sufficient to generate oxygen free radicals for oxidizing the surface of the metal wire 134, and it is not necessary to generate a large amount of oxygen free radicals in a short time (e.g., 10 ms) as in the case of generating oxygen free radicals for cracking precursor ions. Therefore, it is sufficient to use a high-frequency power supply with a lower output than that of the mass spectrometry device of patent document 1, which can reduce costs. Mass spectrometry devices are generally equipped with a high-frequency power supply for applying a high-frequency voltage to electrodes for converging and screening ions. In the mass spectrometry device 200 of modification example 1, such a high-frequency power supply can also be used for the generation of oxygen free radicals (also used as a high-frequency power supply 63). In addition, oxygen free radicals can also be generated by direct current discharge instead of high-frequency discharge, in which case a cheaper direct current power supply can be used.

[0051] In the above embodiment and Modification 1, the metal wire 134 is disposed in the collision chamber 132 to generate oxygen radicals in the collision chamber 132 . However, a configuration in which oxygen radicals are emitted from the metal wire 134 outside the collision chamber 132 may also be employed.

[0052] Figure 4 This is a diagram showing the main structure of a mass spectrometer main body 302 of a mass spectrometer 300 in Modification 2, which generates oxygen radicals outside the collision cell 132, introduces them into the collision cell 132, and attaches them to precursor ions. Components identical to those in the aforementioned embodiment and Modification 1 are denoted by the same reference numerals, and their description will be omitted.

[0053] The mass spectrometer 300 of Modification 2 is characterized by including an oxygen radical generation chamber 21 connected to a collision cell 132, and a metal wire 134 disposed within the oxygen radical generation chamber 21. In the mass spectrometer 300 of Modification 2, oxygen radicals are generated by supplying a predetermined current from a first DC power supply 20 to the metal wire 134, heating the metal wire to a predetermined temperature, as in the aforementioned embodiment and Modification 1. The oxygen radicals generated within the oxygen radical generation chamber 21 flow into the collision cell 132 connected to the oxygen radical generation chamber 21, and attach to precursor ions derived from sample components, thereby generating product ions.

[0054] In the mass spectrometer 300 of Modification 2, the oxygen radical generation chamber 21 only needs to be large enough to accommodate the metal wire 134. Therefore, the compact oxygen radical generation chamber 21 can be positioned near the collision chamber 132, thereby being integrally formed within the main body 302 of the mass spectrometer 300. By positioning the oxygen radical generation chamber 21 adjacent to the collision chamber 132, the oxygen radicals can travel a shorter distance, reducing their disappearance and improving the utilization efficiency of the generated oxygen radicals.

[0055] In the mass spectrometry device 300 of variant example 2, the metal wire 134 is arranged outside the collision chamber 132. Therefore, even if undesired impurities are released from the metal wire 134, the impurities are unlikely to flow into the collision chamber 132, and the wall surface of the collision chamber 132 and the quadrupole ion guide 133 are unlikely to be contaminated by the impurities. In addition, since the structure is to generate oxygen free radicals outside the collision chamber 132, even if a strip wire or porous metal (both metals whose surfaces are covered with oxides) with a volume larger than that of the metal wire 134 is used, there is no need to worry about the ions colliding with them and disappearing. In addition, in Figure 4 In the embodiment, the oxygen radical generating / irradiating unit 6 is used to form an oxide on the surface of the metal wire 134 during non-measurement, as in Modification 1. However, the oxygen supply unit 4 can also be used as in the above-mentioned embodiment. In this case, an electrode for generating discharge in the oxygen radical generating chamber 21 and an electrode for applying a predetermined voltage to the electrode can be provided as needed.

[0056] The above-described embodiment and modified examples are all configured as triple quadrupole mass spectrometers, but the present invention can also be applied to mass spectrometers of other structures. As one such mass spectrometer, an ion trap-time-of-flight mass spectrometer can be cited. The internal space of the ion trap is generally larger than the internal space of the collision chamber 132 of the mass spectrometer 1 of the above-described embodiment or the mass spectrometer 200 of the modified example. Therefore, a stripline having a larger volume and surface area than the metal wire 134 of the above-described embodiment or modified example can be used. In the case of an ion trap-time-of-flight mass spectrometer, it is also possible to configure the ion trap-time-of-flight mass spectrometer to oxidize the surface of the metal wire or stripline, as in the above-described embodiment, or to configure the ion trap-time-of-flight mass spectrometer to oxidize the surface of the metal wire or stripline, as in the above-described embodiment, by supplying oxygen into the ion trap. Alternatively, it is possible to configure the ion trap-time-of-flight mass spectrometer to oxidize the surface of the metal wire or stripline, as in the above-described modified example.

[0057] In addition, in the above-mentioned embodiment and modification, platinum whose surface is covered with oxide is used as the metal wire 134, but a metal wire composed of a metal other than platinum can also be used. For example, a metal wire composed of tungsten or copper can also be used as described in Non-Patent Document 1. When using these, the temperature at which oxygen free radicals are released from their oxides can be determined in advance through preliminary experiments, as in the above-mentioned embodiment, and this temperature can be used as the above-mentioned prescribed temperature. However, when using a noble metal, it is difficult to release unwanted impurities other than oxygen free radicals, and the surface of the quadrupole ion guide 133 in the collision chamber 132 is not easily contaminated. Therefore, it is preferable to use a metal wire composed of a noble metal such as platinum, as in the above-mentioned embodiment.

[0058] Furthermore, while the above-described embodiments and variations describe structures that release oxygen radicals from metal oxides, it is also possible to configure the system to release nitrogen radicals from metal nitrides. For example, a metal wire or ribbon made of platinum, its surface coated with platinum nitride, can be placed inside a collision cell or ion trap and heated to a predetermined temperature. This allows nitrogen radicals to attach to precursor ions within the collision cell or ion trap, thereby generating product ions. In this case, a nitrogen tank can be used in place of the oxygen tank 41 used in the above-described embodiment, or a nitrogen radical generation / irradiation unit can be used in place of the oxygen radical generation / irradiation unit 6 used in the above-described variations.

[0059] Furthermore, in the above-described embodiment, the ESI probe 101 for ionizing a liquid sample is used as an ionization source, but any ionization source appropriate to the form or characteristics of the sample being measured may be used. For example, in the case of a gaseous sample, an electron ionization source may be used, and in the case of a biological sample, a matrix-assisted laser desorption ionization source (MALDI source) may be used. Furthermore, while the above-described embodiment and modifications are all mass spectrometers that separate and measure ions based on mass-to-charge ratio, the present invention can also be applied to ion analyzers that separate and measure ions based on mobility.

[0060] Next, the results of measurements performed using the mass spectrometer 1 of the above-described embodiment will be described.

[0061] Figure 5This is a mass spectrum (product ion spectrum) obtained by measuring the product ions generated by the fragmentation of precursor ions derived from the phospholipid PC18:1(9Z). In this measurement, a platinum wire (metal wire) with a diameter of 0.1 and a length of 50 mm, which has been previously surface-oxidized, is placed in the collision chamber 132. A current of 0.6 A is passed through the platinum wire to heat it to approximately 1000°C, thereby releasing atomic radicals (atomic oxygen). In this measurement, the platinum wire is placed in an oxygen plasma generated by high-frequency discharge in a vacuum chamber independent of the mass spectrometer 1 for one hour, thereby performing surface oxidation. Of course, surface oxidation treatment is not limited to this method; for example, oxidation can also be performed in a liquid phase, as used in the manufacture of Adams catalysts.

[0062] Figure 5 The product ion spectrum shown shows a mass peak with a mass-to-charge ratio of 690. This peak is the mass of the product ion generated by the fragmentation of the molecular ion (precursor ion) of the phospholipid PC18:1(9Z) at the position of the carbon-carbon unsaturated bond. As described in Patent Document 2, oxygen radicals specifically fragment hydrocarbon chains at the position of the carbon-carbon unsaturated bond. In other words, it can be seen that, in the mass spectrometer 1 of this embodiment, similarly to Patent Document 2, oxygen radicals attach to precursor ions to generate product ions, resulting in an oxygen attachment dissociation (OAD) spectrum.

[0063] In addition, when the above-mentioned measurement is repeated while continuously releasing oxygen free radicals from the platinum wire, an OAD spectrum is obtained from a platinum wire with a diameter of 0.1 for about 1 hour. The larger the surface area of the radical emitter that releases oxygen free radicals, the faster and more oxygen free radicals can be released. In this regard, for example, it is preferred to use the strip wire described in the above-mentioned modification. In addition, the surface area can also be made larger by using porous metal. For example, it is believed that if 8 strip wires with a width of 6 mm are set in the collision chamber, MS / MS measurements can be performed for about 500 hours. As an example, if it is believed that one LC analysis is about 20 minutes, by using such a strip wire, 1500 LC-MS / MS analyses can be performed continuously.

[0064] [Way]

[0065] It will be understood by those skilled in the art that the above-described multiple exemplary embodiments are specific examples of the following aspects.

[0066] (Item 1)

[0067] An analysis device according to one embodiment generates product ions from precursor ions derived from sample components and analyzes the product ions, and includes:

[0068] a reaction chamber into which the precursor ions are introduced;

[0069] a radical emitter disposed in the reaction chamber or in a space communicating with the reaction chamber, wherein at least a portion of the surface of the radical emitter is oxidized or nitrided and the radical emitter is composed of a predetermined type of metal;

[0070] a heating unit that heats the radical emitter to a predetermined temperature; and

[0071] The separation and detection unit separates and detects product ions generated from the precursor ions by the reaction between the precursor ions and radicals emitted from the radical emitter heated to the predetermined temperature, based on at least one of a mass-to-charge ratio and an ion mobility.

[0072] In the ion analysis device described in the first item, oxygen radicals or nitrogen radicals are generated by heating a radical emitter composed of a specified metal, at least a portion of whose surface is oxidized or nitrided, to a specified temperature. The radical emitter can be, for example, a platinum wire coated with platinum oxide. In this case, the radical emitter can be heated to approximately 200°C by supplying a few watts of DC power, thereby generating oxidized radicals. In other words, the specified temperature is the temperature at which oxygen radicals can be emitted from the radical emitter, and this temperature is predetermined based on prior knowledge or preliminary experiments. The radical emitter is located in a reaction chamber or a space connected to the reaction chamber, so that radicals are supplied to the reaction chamber, and product ions are generated from the precursor ions through the reaction between the precursor ions and the radicals. The generated product ions are separated and detected by a separation and detection unit based on at least one of the mass-to-charge ratio and the ion mobility. The ion analyzer according to the present invention does not require a power supply for supplying high-output high-frequency power as in conventional ion analyzers, and therefore can irradiate sample molecules with oxygen radicals or nitrogen radicals at low cost.

[0073] (Second Item)

[0074] In the ion analysis device described in the first item,

[0075] The radical emitter is platinum at least a portion of which is oxidized.

[0076] Heating easily oxidizable metals can release unintended impurities, potentially contaminating the reaction chamber. In the ion analyzer described in the second item, platinum, a noble metal, is used as the metal constituting the radical emitter. Therefore, impurities other than oxygen radicals are less likely to be emitted from the radical emitter, reducing the possibility of contamination of the reaction chamber.

[0077] (Item 3)

[0078] In the ion analysis device described in the first or second item,

[0079] The radical emitter is a strip line.

[0080] (Item 4)

[0081] In the ion analysis device described in the first or second item,

[0082] The radical emitter is a metal wire.

[0083] The radical emitter is used to emit oxygen or nitrogen radicals from the oxide or nitride formed on its surface. Therefore, a large surface area of the radical emitter can improve radical generation efficiency. In the ion analyzer described in the third or fourth item, a linear ribbon or wire is used as the radical emitter. This increases the surface area of the radical emitter, enabling efficient radical emission. In particular, the use of a compact wire in the fourth item reduces the likelihood of precursor or product ions colliding with the radical emitter and being eliminated.

[0084] (Item 5)

[0085] The ion analysis device according to any one of the first to fourth items further comprises:

[0086] an electrode disposed in the reaction chamber to control the behavior of ions in the reaction chamber; and

[0087] The second heating unit heats the electrode to a predetermined temperature.

[0088] In most cases, the reaction chamber is a three-dimensional ion trap or linear ion trap (collision cell), which has electrodes for capturing or screening ions. When some of the oxygen or nitrogen radicals emitted from the radical emitter adhere to such electrodes, the electric field formed by applying a DC voltage and / or a high-frequency voltage to these electrodes is disrupted, potentially making it impossible to accurately control the behavior of the ions. In the ion analysis device described in item 5, by heating such electrodes to a predetermined temperature, oxidation or nitridation of the electrode surfaces can be suppressed, reducing the possibility of disruption in the electric field formed by these electrodes.

[0089] (Item 6)

[0090] In the ion analysis device described in the fifth item,

[0091] The surface of the electrode is gold or platinum.

[0092] In the ion analysis device described in the sixth aspect, by using electrodes whose surfaces are made of gold or platinum, the possibility of oxidation or nitridation can be further reduced.

[0093] (Item 7)

[0094] In the ion analysis device described in any one of the first to sixth items,

[0095] The invention further includes an oxidation reactant supply unit that supplies an oxidation reactant for oxidizing the surface of the radical emitter to a space where the radical emitter is arranged.

[0096] As oxygen radicals are released from the surface of the radical emitter, the oxide disappears. In the ion analyzer described in Item 7, the surface of the radical emitter is oxidized by the oxidation reactant, thereby achieving a state in which oxygen radicals can be repeatedly released.

[0097] (Item 8)

[0098] In the ion analysis device described in item 7,

[0099] The oxidation reaction product supply unit includes an oxygen supply unit that supplies oxygen to a space where the radical emitter is arranged.

[0100] In the ion analysis apparatus described in Item 8, oxygen gas is supplied to the space (the reaction chamber or the space communicating with the reaction chamber) where the radical emitter is arranged, so that the surface of the radical emitter can be oxidized by the oxygen gas.

[0101] (Item 9)

[0102] In the ion analysis device described in item 8,

[0103] The oxidation reaction product supply unit further includes a discharge unit that generates direct current discharge or high-frequency discharge in a space where the radical emitter is arranged.

[0104] In the ion analyzer described in Item 9, direct current discharge or high frequency discharge is generated in the space (reaction chamber or space connected to the reaction chamber) where the radical emitter is arranged to generate oxygen radicals, thereby efficiently oxidizing the surface of the radical emitter.

[0105] (Item 10)

[0106] In the ion analysis device described in item 7,

[0107] The oxidation reaction product supply unit includes:

[0108] an oxygen radical generating unit that generates oxygen radicals outside the space where the radical emitter is arranged; and

[0109] An oxygen radical introduction unit introduces the oxygen radicals generated by the oxygen radical generation unit into the space where the radical emitter is arranged.

[0110] In the ion analysis device described in Item 10, oxygen radicals generated outside the space (a reaction chamber or a space connected to the reaction chamber) where the radical emitter is located are introduced into the space, thereby oxidizing the surface of the radical emitter. Furthermore, in the radical generating unit that generates oxygen radicals for fragmenting precursor ions, a large amount of oxygen radicals must be generated in a short period of time, necessitating the use of high-output high-frequency power to generate discharge. However, oxidizing the surface of the radical emitter does not require such a large amount of oxygen radicals. Therefore, it is sufficient to generate free radicals by generating discharge using DC power or low-output high-frequency power.

[0111] Description of Reference Numerals

[0112] 1. 200, 300: mass spectrometer; 2. 202, 302: mass spectrometer body; 10: ionization chamber; 101: ESI probe; 102: desolvation tube; 11: first intermediate vacuum chamber; 111: ion lens; 112: separator; 12: second intermediate vacuum chamber; 121: ion guide; 13: analysis chamber; 131: front quadrupole mass filter; 132: collision chamber; 133: quadrupole ion guide; 134: metal wire; 135: rear quadrupole mass filter; 136: ion detector; 20: first DC power supply; 21: oxygen free radical generation Chamber; 30: Second DC power supply; 4: Oxygen supply unit; 41: Oxygen tank; 42: Oxygen inlet flow path; 43: Valve; 5: Control / processing unit; 51: Storage unit; 52: Analysis control unit; 53: Analysis processing unit; 54: Oxidation reaction control unit; 55: Input unit; 56: Display unit; 6: Oxygen free radical generation / irradiation unit; 61: Free radical generation chamber; 63: High-frequency power supply; 64: Nozzle; 641: Ground electrode; 642: Torch; 643: Needle electrode; 644: Connector; 66: Oxygen tank; 661: Valve; 67: Vacuum pump; 68: Delivery pipe; 681: Head.

Claims

1. An ion analysis device for generating product ions from precursor ions derived from a sample component and analyzing the product ions, the ion analysis device comprising: a reaction chamber into which the precursor ions are introduced; a radical emitter disposed in the reaction chamber or in a space communicating with the reaction chamber, wherein at least a portion of the surface of the radical emitter is oxidized or nitrided and the radical emitter is composed of a predetermined type of metal; A heating unit is configured to heat the radical emitter to a predetermined temperature, wherein: The predetermined temperature is a temperature at which free radicals can be released from the free radical emitter; as well as The separation and detection unit separates and detects product ions generated from the precursor ions by the reaction between the precursor ions and radicals emitted from the radical emitter heated to the predetermined temperature, based on at least one of a mass-to-charge ratio and an ion mobility.

2. The ion analysis device according to claim 1, characterized in that The radical emitter is platinum at least a portion of which is oxidized.

3. The ion analysis device according to claim 1, wherein The radical emitter is a strip line.

4. The ion analysis device according to claim 1, characterized in that The radical emitter is a metal wire.

5. The ion analysis device according to claim 1, characterized in that Also features: an electrode disposed in the reaction chamber to control the behavior of ions in the reaction chamber; and The second heating unit heats the electrode to a predetermined temperature.

6. The ion analysis device according to claim 5, characterized in that The surface of the electrode is gold or platinum.

7. The ion analysis device according to claim 1, characterized in that The invention further includes an oxidation reactant supply unit that supplies an oxidation reactant for oxidizing the surface of the radical emitter to a space where the radical emitter is arranged.

8. The ion analysis device according to claim 7, characterized in that The oxidation reaction product supply unit includes an oxygen supply unit that supplies oxygen to a space where the radical emitter is arranged.

9. The ion analysis device according to claim 8, characterized in that The oxidation reaction product supply unit further includes a discharge unit that generates direct current discharge or high-frequency discharge in a space where the radical emitter is arranged.

10. The ion analysis device according to claim 7, characterized in that The oxidation reaction product supply unit includes: an oxygen radical generating unit that generates oxygen radicals outside the space where the radical emitter is arranged; and An oxygen radical introduction unit introduces the oxygen radicals generated by the oxygen radical generation unit into the space where the radical emitter is arranged.

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