Mass analysis method and mass analysis device

Abstract

Provided is a method for performing mass spectrometry in which precursor ions from sample components and radicals are made to react in a reaction chamber 132, thereby generating product ions from the precursor ions, the method including: a step 6 for generating radicals from a source gas; a step 8 for introducing the radicals and precursor ions into the reaction chamber 132 while power of an amount that corresponds to a generation condition of the radicals is fed to a temperature control unit 1331 provided in the reaction chamber 132; and a step 9 for separating and detecting the product ions in accordance with the mass-to-charge ratio, the product ions being generated from the precursor ions in the reaction chamber 132.

Description

[Technical field]

[0001] The present invention relates to a mass spectrometry method and a mass spectrometry apparatus. [Background technology]

[0002] Mass spectrometry is widely used to identify polymer compound components in a sample and analyze their structures. In this method, ions with a specific mass-to-charge ratio are selected as precursor ions from ions derived from the sample components, and various product ions are generated by dissociating the precursor ions and separating them according to their mass-to-charge ratios.

[0003] Many polymer compounds are organic substances whose main skeleton is a hydrocarbon chain. To know the characteristics of a polymer compound, it is effective to obtain information such as the presence or absence of unsaturated bonds of carbon atoms and the presence or absence of characteristic functional groups. Recently, a radical attachment dissociation method has been proposed in which a radical is attached to a precursor ion derived from a sample component such as a protein or peptide, thereby dissociating the precursor ion at the position of a specific functional group, or a radical is attached to a precursor ion derived from a sample component having a hydrocarbon chain containing an unsaturated bond of carbon atoms, thereby dissociating the precursor ion at the position of the unsaturated bond. For example, Patent Documents 1 and 2 and Non-Patent Document 1 describe selectively dissociating a precursor ion at the position of a peptide bond by attaching a hydrogen radical to the precursor ion. Patent Documents 3 and 4 also describe selectively dissociating a precursor ion at the position of an unsaturated bond contained in a hydrocarbon chain by attaching an oxygen radical or a hydroxyl radical to the precursor ion.

[0004] The reaction efficiency of precursor ions and radicals varies depending on the magnitude of the kinetic energy of the precursor ions and radicals. Therefore, if the temperature of the reaction chamber into which the precursor ions and radicals are introduced is different, the type and amount of product ions generated will differ even if the same types of precursor ions and radicals are reacted. Therefore, in the past, attempts have been made to generate desired product ions by heating and maintaining the reaction chamber at a predetermined temperature (e.g., about 130°C) using a heater attached to the reaction chamber. In addition, by heating the reaction chamber, it is possible to prevent sample components and substances derived from radicals from adhering to and contaminating the members constituting the reaction chamber. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2015 / 133259 [Patent Document 2] International Publication No. 2018 / 186286 [Patent Document 3] International Publication No. 2019 / 155725 [Patent Document 4] International Publication No. 2020 / 240908 [Non-patent literature]

[0006] [Non-Patent Document 1] Takahashi, Hidenori, et al. "Hydrogen Attachment / Abstraction Dissociation (HAD) of Gas-Phase Peptide Ions for Tandem Mass Spectrometry." Analytical chemistry 88.7 (2016): 3810-3816. Summary of the Invention [Problem to be solved by the invention]

[0007] Patent Documents 2 and 3 describe a method in which precursor ions are captured in an ion trap, a raw material gas is introduced into a radical generation chamber to generate plasma of the raw material gas, and the radicals generated by the introduction are introduced into a reaction chamber (ion trap) to react the precursor ions with the radicals. Patent Document 4 describes a method in which radicals generated in the same manner as above are introduced into the inside of a reaction chamber (collision cell), while precursor ions are introduced into the ion trap to react the precursor ions with the radicals. In the radical generation unit that generates plasma of the raw material gas as described above, a part of the raw material gas introduced into the radical generation chamber does not become either plasma or radicals, but remains unreacted, and is introduced into the reaction chamber together with the radicals. Usually, the temperature of the raw material gas introduced into the radical generation chamber is lower than the temperature inside the reaction chamber, so that the temperature inside the reaction chamber drops when the raw material gas is introduced from the radical generation chamber. As a result, the precursor ions are cooled in the reaction chamber and their kinetic energy is reduced, which causes a problem that desired product ions cannot be generated, or even if they are generated, the generation efficiency is reduced.

[0008] Also, Non-Patent Document 1 describes a method in which hydrogen gas is introduced into a tungsten capillary heated to a high temperature of 2000°C, pyrolyzed to generate hydrogen radicals, and then introduced into a reaction chamber to react with precursor ions. In this case, the reaction chamber is heated by the inflow of unreacted hydrogen gas heated to a high temperature. As a result, the precursor ions in the reaction chamber are heated and their kinetic energy increases, causing the precursor ions to dissociate at positions other than the peptide bond, resulting in a problem of poor efficiency in generating desired product ions.

[0009] The problem to be solved by the present invention is to provide a technology capable of suppressing temperature changes in a reaction chamber when radicals are supplied in an ion analyzer that analyzes precursor ions derived from sample components by irradiating them with radicals. [Means for solving the problem]

[0010] One aspect of the present invention, which has been made to solve the above problems, is a method for performing mass spectrometry by generating product ions from precursor ions derived from a sample component by reacting the precursor ions with radicals in a reaction chamber, the method comprising the steps of: generating radicals from a source gas; introducing the radicals and precursor ions into the reaction chamber while supplying power in an amount corresponding to the radical generation conditions to a temperature adjustment unit provided in the reaction chamber; separating and detecting product ions generated from the precursor ions in the reaction chamber according to their mass-to-charge ratios; Includes.

[0011] In order to solve the above problems, the mass spectrometer according to the present invention comprises: a reaction chamber into which precursor ions are introduced; A temperature control unit provided in the reaction chamber; A power supply unit that supplies power to the temperature adjustment unit; a radical generating unit that generates radicals from a raw material gas and introduces the radicals into the reaction chamber; a measurement control unit that controls the operation of the power supply unit and the radical generation unit and supplies the temperature adjustment unit with power in an amount corresponding to the radical generation conditions in the radical generation unit during a time period when the radicals are introduced into the reaction chamber; a mass separation unit that separates product ions generated from the precursor ions in the reaction chamber according to their mass-to-charge ratios; an ion detector that detects ions separated by the mass separator; Equipped with. Effect of the Invention

[0012] The temperature control unit is usually a heater, but when it is necessary to cool the reaction chamber, for example when a heated source gas is introduced into the reaction chamber, a unit having both heating and cooling functions, such as a unit equipped with both a Peltier element and a heater, may be used. The radical generation unit may be, for example, a unit that generates radicals from plasma of a source gas, or a unit that generates radicals by thermally dissociating a source gas. The radical generation conditions may include a radical generation method, a supply amount of the source gas, and a type of the source gas.

[0013] In the mass analysis method and mass analysis apparatus according to the present invention, during the time period when radicals are introduced into the reaction chamber into which precursor ions are introduced, an amount of power according to the radical generation conditions is supplied to the temperature adjustment unit. For example, when low-temperature source gas flows into the reaction chamber together with the radicals, the amount of power supplied to the temperature adjustment unit (heater, etc.) is increased. On the other hand, when source gas having a temperature higher than the above-mentioned predetermined temperature flows into the reaction chamber together with the radicals, the amount of power supplied to the temperature adjustment unit (heater) is decreased. Alternatively, when source gas with an even higher temperature flows into the reaction chamber, power is supplied to the temperature adjustment unit (e.g., a Peltier element) to cool the reaction chamber.

[0014] In the mass spectrometry method and mass spectrometry apparatus of the present invention, when radicals are supplied to the reaction chamber, an amount of power corresponding to the radical generation conditions is supplied to the temperature adjustment unit, thereby compensating for temperature changes in the reaction chamber due to the raw material gas flowing into the reaction chamber together with the radicals, thereby suppressing undesirable temperature changes in the reaction chamber when radicals are supplied. [Brief description of the drawings]

[0015] [Figure 1] 1 is a diagram showing the configuration of a main portion of a liquid chromatograph mass spectrometer including an embodiment of a mass spectrometer according to the present invention; [Diagram 2] FIG. 2 is a configuration diagram of a radical production unit included in the mass spectrometer of the present embodiment. [Diagram 3] 4 is an example of heater power information used in the mass spectrometer and mass analysis method of the present embodiment. [Figure 4]1 is a flowchart of an embodiment of a mass spectrometry method according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of a mass spectrometer and a mass spectrometric method according to the present invention will be described with reference to the drawings.

[0017] FIG. 1 is a diagram showing the configuration of the main parts of a liquid chromatograph mass spectrometer 100 in which a mass spectrometer 1 according to the present embodiment is combined with a liquid chromatograph 2. As shown in FIG.

[0018] The liquid chromatograph 2 includes a mobile phase container 20 that contains a mobile phase, a liquid delivery pump 21 that delivers the mobile phase, an injector 22, and a column 23. In addition, an autosampler 24 that introduces a plurality of liquid samples into the injector 22 in a predetermined order is connected to the injector 22.

[0019] The mass spectrometer 1 comprises a main body consisting of an ionization chamber 10, which is at approximately atmospheric pressure, and a vacuum chamber, and a control / processing unit 7. Inside the vacuum chamber, in order from the ionization chamber 10 side, there are a first intermediate vacuum chamber 11, a second intermediate vacuum chamber 12, a third intermediate vacuum chamber 13, and an analysis chamber 14, and the structure has a multi-stage differential pumping system in which the degree of vacuum increases in this order.

[0020] An electrospray ionization probe (ESI probe) 101 that applies an electric charge to a liquid sample and sprays it is installed in the ionization chamber 10. Sample components separated in the column 23 of the liquid chromatograph 2 are sequentially introduced into the ESI probe 101.

[0021] The ionization chamber 10 and the first intermediate vacuum chamber 11 communicate with each other through a thin-diameter heated capillary 102. In the first intermediate vacuum chamber 11, an ion guide 111 made up of multiple rod electrodes is arranged so as to surround an ion optical axis C, which is the central axis in the flight direction of the ions. Ions that enter the first intermediate vacuum chamber 11 from the ionization chamber 10 are converged near the ion optical axis C by the electric field formed by the ion guide 111.

[0022] 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. A plurality of rod electrodes are also arranged in the second intermediate vacuum chamber 12 so as to surround the ion optical axis C. Ions that enter the second intermediate vacuum chamber 12 from the first intermediate vacuum chamber 11 are focused near the ion optical axis C by the electric field formed by the ion guide 121.

[0023] In the third intermediate vacuum chamber 13, there are disposed a quadrupole mass filter 131 that separates ions according to their mass-to-charge ratio, a collision cell 132 equipped with a multipole ion guide 133 therein, and an ion guide 134. In the collision cell 132, there is disposed a temperature sensor 1321 for measuring the temperature inside the collision cell 132.

[0024] The ion guide 134 transports the ions emitted from the collision cell 132 to the rear while converging them near the ion optical axis C. The multipole ion guide 133 is usually made of metal. In many cases, a stainless steel ion guide is used. Preferably, a gold- or platinum-plated metal ion guide is used. A heater 1331 for heating the multipole ion guide 133 is connected to the multipole ion guide 133. The temperature sensor 1321 and the heater 1331 may be placed at appropriate locations as long as they can measure the temperature inside the collision cell 132 and heat the inside of the collision cell 132 to a predetermined temperature.

[0025] The collision cell 132 is connected to the radical supply unit 5. FIG. 2 shows a detailed configuration of the radical supply unit 5. The radical supply unit 5 includes a radical source 54 having a radical generation chamber 51 formed therein, a vacuum pump (not shown) for evacuating the radical generation chamber 51, a raw material gas supply source 52 for supplying a gas (raw material gas) that is a raw material for radicals, and a high-frequency power supply unit 53. A mass flow controller (MFC) 56 for adjusting the flow rate of the raw material gas is provided in a flow path from the raw material gas supply source 52 to the radical generation chamber 51. The raw material gas may be, for example, water vapor, oxygen gas, nitrogen gas, hydrogen gas, carbon dioxide, air, or the like, depending on the type of radicals to be generated.

[0026] The radical source 54 has a tubular body 541 made of a dielectric material, and its internal space serves as the radical generation chamber 51. The tubular body 541 is inserted into a hollow cylindrical magnet 544 and fixed in place by a plunger 545. A spiral antenna 542 (indicated by a broken line in FIG. 2) is wound around the outer periphery of the portion of the tubular body 541 located inside the magnet 544.

[0027] The radical source 54 is also provided with a high-frequency power input unit 546. High-frequency power is supplied to the high-frequency power input unit 546 from the high-frequency power supply unit 53. The radical source 54 is further provided with a flange 547 for fixing a tip portion of the radical source 54. A hollow cylindrical magnet 548 having the same diameter as the magnet 544 is accommodated inside the flange 547 and pairs with the magnet 544. The magnets 544 and 548 generate a magnetic field inside the tubular body 541 (radical generation chamber 51), and the action of this magnetic field makes it easy to generate and maintain plasma.

[0028] A transport pipe 58 is connected to the outlet end of the radical source 54 for transporting the radicals generated in the radical generation chamber 51 to the collision cell 132. The transport pipe 58 is preferably an insulating pipe, and for example, a quartz glass pipe or a borosilicate glass pipe can be used.

[0029] The analysis chamber 14 is equipped with an ion transport electrode 141 for transporting the ions incident from the third intermediate vacuum chamber 13, an orthogonal acceleration electrode 142 consisting of a pair of pusher electrode 1421 and puller electrode 1422 arranged opposite to each other across the ion incident optical axis (orthogonal acceleration region), an acceleration electrode 143 for accelerating the ions sent out to the flight space by the orthogonal acceleration electrode 142, a reflectron electrode 144 for forming a return trajectory of the ions in the flight space, an ion detector 145, and a flight tube 146 for defining the outer edge of the flight space. The traveling direction of the ions that have entered the analysis chamber 14 is deflected toward the flight space by the orthogonal acceleration electrode 142. The ions whose traveling direction has been deflected are accelerated by the acceleration electrode 143 and enter the flight space, and after flying a return trajectory for a flight time corresponding to the mass-to-charge ratio of each ion, are detected by the ion detector 145.

[0030] The control / processing unit 7 controls the operation of each of the above-mentioned units, and has the function of storing data obtained by the ion detector 145 and creating and analyzing chromatograms and mass spectra. The control / processing unit 7 includes a storage unit 71, and further includes a measurement condition setting unit 72 and a measurement control unit 73 as functional blocks. The actual entity of the control / processing unit 7 is a general computer, and the above-mentioned functional blocks are realized by executing a pre-installed mass analysis program on a processor. In addition, an input unit 8 including a mouse, keyboard, etc., and a display unit 9 including a liquid crystal display, etc. are connected to the control / processing unit 7.

[0031] The storage unit 71 stores a method file that describes measurement parameters (retention time of the target compound, type and generation conditions of the radical used, mass-to-charge ratio of precursor ion, etc.) for measuring each of the target compounds. The radical generation conditions include the type and flow rate of the source gas used for generating the radical. In addition, for each of the multiple types of radicals, information (heater power information) that associates the flow rate of the source gas used for generating the radical, the amount of power supplied to the heater 1331 when supplying the source gas at the flow rate, and the timing of starting and ending the supply of the amount of power is stored. FIG. 3 is an example of the heater power information. The timing of starting the supply of the amount of power is set with respect to the start and end of the supply of the source gas. Specifically, for example, the supply of the source gas is started after a first time (e.g., 30 seconds) has elapsed since the start of the supply of the amount of power, and the supply of the source gas is stopped after a second time (e.g., 1 minute) has elapsed since the end of the supply of the amount of power.

[0032] Next, as an example of the mass analysis method according to the present invention, the procedure of analysis using the liquid chromatograph mass spectrometer 100 of this embodiment will be described. FIG. 4 is a flow chart showing the procedure of analysis. In the liquid chromatograph mass spectrometer 100 of this embodiment, while the power supply of the main body is turned on, even during a time period (standby time) when analysis is not performed, power is supplied from the power supply 137 to the heater 1331, and the inside of the collision cell 132 is controlled (Proportional-Integral-Differential Control: PID control) to be maintained at a predetermined temperature (for example, 130° C.) (step 1). The amount of power supplied at this time is also referred to as the PID power amount hereinafter. The PID power amount changes depending on the difference between the temperature measured by the temperature sensor 1321 and the above-mentioned predetermined temperature.

[0033] When the user instructs the start of analysis by a predetermined input operation, the measurement condition setting unit 72 displays a screen for setting the measurement conditions on the screen of the display unit 9. When the user specifies a target compound through the screen, the measurement condition setting unit 72 reads out the measurement parameters of the target compound from the storage unit 71 and displays them on the screen of the display unit 9 together with heater power information (the amount of power supplied to the heater 1331 and the timing of starting and ending the supply of the amount of power) corresponding to the type of radical contained therein and the generation conditions (type of raw material gas, flow rate, etc.). The user checks the displayed contents and changes the measurement parameters and the amount of power supplied to the heater 1331 as necessary. When the user determines the measurement conditions including the measurement parameters and the amount of power (step 2), the measurement condition setting unit 72 creates a batch file reflecting the information and stores it in the storage unit 71. Note that if a measurement using the same measurement parameters, etc. has been performed in the past, the user may specify a batch file stored in the storage unit 71. The amount of power determined here is also referred to as the amount of power during gas supply hereinafter. Here, the user is required to confirm and determine the measurement conditions including the measurement parameters and the amount of power supplied to the heater 1331. However, the process of confirmation and determination by the user may be omitted, and a batch file may be created by directly using previously saved data.

[0034] Thereafter, when the user places a liquid sample in the autosampler 24 and instructs the start of measurement (step 3), the measurement control unit 73 controls the operation of each part based on the contents written in the batch file to perform the measurement operation as follows.

[0035] First, the amount of power supplied from the power source 137 to the heater 1331 is changed from the PID power amount to the power amount during gas supply (step 4). Here, it is expressed as changing from the PID power amount to the power amount during gas supply, but in reality, it is possible to continue the PID control itself during gas supply, and to supply to the heater 1331 an amount of power obtained by increasing or decreasing (offsetting) a predetermined amount of power from the PID power amount according to the power amount during gas supply during gas supply. In other words, when PID control is released during gas supply, the power amount during gas supply can be set as an absolute value, or when PID control is continued during gas supply, the power amount during gas supply can be set as an offset amount from the PID power amount.

[0036] After the power amount is changed to that for gas supply, when the first time described in the batch file has elapsed (YES in step 5), the raw material gas is introduced from the raw material gas supply source 52 into the radical generation chamber 51, and high frequency power is input from the high frequency power supply unit 53 to the spiral antenna 542 (step 6). This generates plasma inside the radical generation chamber 51, and radicals are generated from the raw material gas. The radicals generated in the radical generation chamber 51 flow into the collision cell 132 through the transport pipe 58.

[0037] Next, the liquid sample set in the autosampler 24 is introduced into the injector 22 of the liquid chromatograph 2 (step 7). The liquid sample introduced into the injector 22 is carried along with the flow of the mobile phase into the column 23, where it is separated into individual compounds and sequentially introduced into the ESI probe 101.

[0038] Ions of the target compound generated in the ESI probe 101 are drawn into the first intermediate vacuum chamber 11 through the heated capillary 102 due to the pressure difference between the ionization chamber 10 and the first intermediate vacuum chamber 11. In the first intermediate vacuum chamber 11, the ions are focused in the vicinity of the ion optical axis C by the ion guide 111. The ions focused in the first intermediate vacuum chamber 11 then enter the second intermediate vacuum chamber 12, and are again focused in the vicinity of the ion optical axis C by the ion guide 121, before entering the third intermediate vacuum chamber 13. In the third intermediate vacuum chamber 13, precursor ions are selected from the ions generated from the target compound by the quadrupole mass filter 131. The precursor ions that have passed through the quadrupole mass filter 131 are introduced into the collision cell 132 (step 8).

[0039] Inside the collision cell 132, radicals supplied from the radical generation chamber 51 through the transport tube 58 attach to precursor ions. This causes a radical attachment reaction, dissociating the precursor ions to generate product ions. Alternatively, adduct ions to which radicals are attached may be generated. In the following explanation, adduct ions are also referred to as product ions.

[0040] The product ions that have entered the analysis chamber 14 are transported to the orthogonal acceleration electrode 142 by the ion transport electrode 141. A voltage is applied to the orthogonal acceleration electrode 142 at a predetermined period, and the flight direction of the ions is deflected in a direction that is approximately orthogonal to the previous direction. The ions whose flight direction has been deflected are accelerated by the acceleration electrode 143 and sent out into the flight space. The ions sent out into the flight space fly along a predetermined flight path defined by the reflectron electrode 144 and the flight tube 146 for a time according to the mass-to-charge ratio of each ion, and are separated from each other and detected by the ion detector 145 (step 9).

[0041] The ion detector 145 outputs a signal having a magnitude corresponding to the amount of incident ions every time an ion is incident. The output signals from the ion detector 145 are sequentially stored in the memory unit 71. The memory unit 71 stores measurement data based on the flight time of the ions and the detection intensity of the ions.

[0042] When the measurement described in the batch file (if multiple measurements are described, all of the measurements) is completed (YES in step 10), the measurement control unit 73 changes the amount of power supplied from the power source 137 to the heater 1331 from the gas supply power amount to the PID power amount (step 11). After the amount of power supplied to the heater 1331 is changed to the PID power amount, when the second time described in the batch file has elapsed (YES in step 12), the supply of raw material gas from the raw material gas supply source 52 and the supply of high frequency power to the spiral antenna 542 are stopped (step 13). If there is an unexecuted measurement described in the batch file (NO in step 10), return to step 7. Note that, here, it is assumed that the same type of radical is used under the same conditions for the measurement of all samples, but if different types of radicals are irradiated for each sample, or the same radical is irradiated under different conditions, it is sufficient to return to step 4 (shown by a dashed line in FIG. 4).

[0043] In the liquid chromatograph mass spectrometer 100 of this embodiment, the amount of power supplied from the power source 137 to the heater 1331 is changed from the PID amount of power to the amount of power during gas supply based on the heater power information, and after a first time has elapsed, the source gas is supplied to the radical generation chamber 51 and high frequency power is input to the spiral antenna 542 to generate radicals. After the measurement is completed, the amount of power supplied from the power source 137 to the heater 1331 is returned to the PID amount of power, and after a second time has elapsed, the supply to the radical generation chamber 51 and the input of high frequency power to the spiral antenna 542 are stopped.

[0044] When radicals are generated from the raw material gas, only a part of the raw material gas is converted into radicals, and the rest remains unreacted. Normally, the temperature of the raw material gas is lower than the temperature inside the collision cell 132 during PID control, so when the unreacted raw material gas flows into the collision cell 132, the collision cell 132 is cooled and the internal temperature drops. When the internal temperature of the collision cell 132 drops, the precursor ions that have entered the collision cell 132 are cooled and their reactivity drops. As a result, the radical attachment reaction is less likely to occur, the amount of product ions generated decreases, and the measurement sensitivity deteriorates.

[0045] In contrast to this, in this embodiment, heater power information is prepared in advance for each of the multiple types of radicals, which associates the flow rate of the raw material gas used in generating the radical, the amount of power supplied to the heater 1331 when supplying the raw material gas at that flow rate, and the timing for starting and ending the supply of that amount of power, and based on this, the amount of power supplied from the power source 137 to the heater 1331 is increased from the amount of power during PID control, so that even if raw material gas flows in, the temperature of the collision cell 132 is maintained at the temperature during PID control, and the desired radical attachment reaction can be efficiently caused to occur.

[0046] The above embodiment is merely an example and can be modified appropriately in accordance with the spirit of the present invention.

[0047] In the above embodiment, radicals are generated from the raw material gas by generating plasma, but the method of generating radicals is not limited to this. For example, radicals can also be generated by thermally dissociating the raw material gas. In this case, the collision cell 132 is heated by the raw material gas heated to a temperature higher than the collision cell 132 under PID control flowing into the collision cell 132. Therefore, in this case, the amount of power during gas supply should be made smaller than the amount of PID power.

[0048] In the above measurement example, the PID power amount is supplied to the heater 1331 even when not measuring to PID control the temperature of the collision cell 132, but if there is a low possibility that the inside of the collision cell 132 will be contaminated, it is not necessary to supply power to the heater 1331 when not measuring. Also, in the above embodiment, the gas supply power amount is constantly supplied to the heater 1331 during measurement, but it is sufficient to prevent the precursor ions from being cooled at least during the time period when both precursor ions and radicals are introduced into the collision cell 132, that is, during the time period when product ions are generated by the radical attachment reaction, and the gas supply power amount may be supplied only during that time period.

[0049] In the above embodiment, radicals are constantly generated from the raw material gas and supplied to the collision cell 132 during measurement, assuming that plasma is not generated immediately after the supply of raw material gas to the radical generation chamber 51 and the supply of high-frequency power to the spiral antenna 542 are started, and the timing of radical generation may be delayed. However, depending on the type of radicals and the generation conditions, radicals may be generated immediately when the supply of raw material gas to the radical generation chamber 51 and the supply of high-frequency power to the spiral antenna 542 are started. Alternatively, a switching valve that can switch between a flow path for introducing radicals generated in the radical generation chamber 51 into the collision cell 132 and a flow path for discharging them to the outside can be provided in the transport pipe 58. In these cases, radicals can be introduced immediately in accordance with the timing when precursor ions are introduced into the collision cell 132. In other words, the time period during which the raw material gas flows into the collision cell 132 together with radicals is only a part of the entire measurement time (almost the same time period as the time period during which precursor ions are introduced into the collision cell 132), so that the amount of power during gas supply may be supplied to the heater 1331 only during that time period.

[0050] In addition, in the above embodiment, the raw material gas is supplied to the radical generation chamber 51 after the first hour has elapsed since the amount of power was changed to the amount of power during gas supply, and the supply of the raw material gas is terminated after the second hour has elapsed since the amount of power was changed to the PID amount of power. However, if precise temperature control of the collision cell 132 is not required, the change in the amount of power and the start / end of the supply of the raw material gas may be performed simultaneously, or in the reverse order.

[0051] In the above embodiment, precursor ions and radicals were introduced into the collision cell 132 to cause a radical attachment reaction, but a three-dimensional ion trap can be used instead of the collision cell 132. Also, in the above embodiment, a quadrupole mass filter and a time-of-flight mass separator were used as the mass separator, but other types of mass separators may be used. Also, in the above embodiment, a liquid chromatograph and a mass analyzer were combined, but a similar configuration to the above can be used when a gas chromatograph and a mass analyzer are combined, or when only a mass analyzer is used.

[0052] [Aspects] It will be appreciated by those skilled in the art that the above exemplary embodiments are specific examples of the following aspects.

[0053] (Section 1) A mass spectrometry method according to one aspect of the present invention comprises the steps of: A method for performing mass spectrometry by generating product ions from precursor ions derived from a sample component by reacting the precursor ions with radicals in a reaction chamber, comprising the steps of: generating radicals from a source gas; introducing the radicals and precursor ions into the reaction chamber while supplying power in an amount corresponding to the radical generation conditions to a temperature control unit provided in the reaction chamber; separating and detecting product ions generated from the precursor ions in the reaction chamber according to their mass-to-charge ratios; Includes.

[0054] (Section 5) A mass spectrometer according to one aspect of the present invention comprises: a reaction chamber into which precursor ions are introduced; A temperature control unit provided in the reaction chamber; A power supply unit that supplies power to the temperature control unit; a radical generating unit that generates radicals from a raw material gas and introduces the radicals into the reaction chamber; a measurement control unit that controls the operation of the power supply unit and the radical generation unit and supplies the temperature control unit with power in an amount corresponding to the radical generation conditions in the radical generation unit during a period in which the radicals are introduced into the reaction chamber; a mass separation unit that separates product ions generated from the precursor ions in the reaction chamber according to their mass-to-charge ratios; an ion detector that detects ions separated by the mass separator; Equipped with.

[0055] In the mass spectrometry method of paragraph 1 and the mass spectrometry apparatus of paragraph 5, during the time period when radicals are introduced into the reaction chamber into which precursor ions are introduced, an amount of power according to the radical generation conditions is supplied to the temperature control unit. For example, when a low-temperature source gas flows into the reaction chamber together with the radicals, the amount of power supplied to the temperature control unit is increased, and when a source gas having a temperature higher than the above-mentioned predetermined temperature flows into the reaction chamber together with the radicals, the amount of power supplied to the temperature control unit is decreased. In the mass spectrometry method of paragraph 1 and the mass spectrometry apparatus of paragraph 5, when radicals are supplied to the reaction chamber, an amount of power according to the radical generation conditions is supplied to the temperature control unit, thereby compensating for a temperature change in the reaction chamber due to the source gas flowing into the reaction chamber together with the radicals, thereby making it possible to suppress undesired temperature changes in the reaction chamber when the radicals are supplied.

[0056] (Section 2) 2. The mass spectrometry method according to claim 1, During a time period before the start of measurement and / or after the end of measurement, a predetermined amount of power is supplied to the temperature control unit to maintain the reaction chamber at a predetermined temperature, and during part or all of the time period during measurement, the amount of power supplied to the temperature control unit is changed to an amount according to the conditions for generating the radicals.

[0057] In the mass spectrometry method of paragraph 2, the reaction chamber is maintained at a predetermined temperature even during non-measurement periods, so that it is possible to prevent the temperature of the reaction chamber from dropping during measurement standby periods, which would otherwise cause various compounds to adhere to and contaminate the electrodes and other components of the reaction chamber.

[0058] (Section 3) In the mass spectrometry method according to claim 1 or 2, The radical generation conditions include the type of the source gas, the type of radicals generated from the source gas, and the flow rate of the source gas.

[0059] The ratio of radicals generated from the raw material gas in the radical generation section varies depending on the type of raw material gas and the combination of radicals. Also, the amount of raw material gas flowing into the reaction chamber varies depending on the flow rate of the raw material gas supplied to the radical generation chamber. In the mass spectrometry method of paragraph 3, an amount of power is supplied to the temperature control section according to the radical generation conditions including the type of raw material gas, the type of radicals generated from the raw material gas, and the flow rate of the raw material gas, so that the temperature of the reaction chamber can be controlled with higher accuracy.

[0060] (Section 4) 4. The mass spectrometry method according to any one of claims 1 to 3, During the period in which the radicals are introduced into the reaction chamber, regardless of whether the precursor ions are introduced or not, an amount of power according to the radical generation conditions is supplied to the temperature control unit.

[0061] In the mass spectrometry method described in item 4, the temperature of the reaction chamber can be kept constant regardless of whether precursor ions are introduced into the reaction chamber, and therefore, contamination of the electrodes constituting the reaction chamber due to a decrease in the reaction chamber temperature can be suppressed. [Explanation of symbols]

[0062] 100...Liquid chromatograph mass spectrometer 1...Mass spectrometer 10…Ionization chamber 101…ESI probe 102…Heated capillary 11…First intermediate vacuum chamber 111…Ion Guide 112…Skimmer 12...Second intermediate vacuum chamber 121…Ion Guide 13…Third intermediate vacuum chamber 131...Quadrupole mass filter 132…Collision cell 1321...Temperature sensor 133...Multipole ion guide 1331…Heater 134…Ion Guide 14…Analysis room 141...Ion transport electrode 142...Orthogonal acceleration electrode 1421...Extrusion electrode 1422...Pull-in electrode 143...acceleration electrode 144...Reflectron electrode 145…Ion detector 146…Flight tube 2. Liquid chromatograph 5... Radical supply section 51...Radical generation chamber 52…Source gas supply source 53...High frequency power supply unit 54...Radical source 541...Tubular body 542…Spiral antenna 544...Magnet 545...Plunger 546...High frequency power input section 547...Flange 548...Magnet 58...transport pipe 7…Control and processing section 71...Storage section 72…Measurement condition setting section 73...Measurement control section 8...Input section 9…Display section C…Ion optical axis

Claims

1. A method for performing mass spectrometry by generating product ions from precursor ions derived from a sample component by reacting the precursor ions with radicals in a reaction chamber, comprising the steps of: generating radicals from a source gas under predetermined generating conditions; determining, in accordance with the generation conditions, an amount of power that needs to be supplied to a temperature control unit provided in the reaction chamber in order to compensate for a temperature change in the reaction chamber caused by the flow of the raw material gas into the reaction chamber when the radicals are generated under the generation conditions; generating the radicals while supplying power to the temperature control unit in an amount corresponding to the generation conditions of the radicals, and introducing the radicals and precursor ions into the reaction chamber; separating and detecting product ions generated from the precursor ions in the reaction chamber according to their mass-to-charge ratios; A mass spectrometry method comprising:

2. 2. The mass spectrometry method according to claim 1, further comprising: supplying a predetermined amount of power to the temperature control unit during a period before the start of measurement and / or after the end of measurement to maintain the reaction chamber at a predetermined temperature; and changing the amount of power supplied to the temperature control unit during part or all of the period during measurement to an amount according to the radical generation conditions.

3. 2. The mass spectrometry method according to claim 1, wherein the radical generation conditions include the type of the source gas, the type of radicals generated from the source gas, and a flow rate of the source gas.

4. The mass spectrometry method according to claim 1 , wherein during a period in which the radicals are introduced into the reaction chamber, an amount of power corresponding to a generation condition of the radicals is supplied to the temperature control unit, regardless of whether the precursor ions are introduced or not.

5. a reaction chamber into which precursor ions are introduced; A temperature control unit provided in the reaction chamber; A power supply unit that supplies power to the temperature control unit; a radical generating unit that generates radicals from a raw material gas under predetermined generating conditions and introduces the radicals into the reaction chamber; a storage unit in which an amount of power that needs to be supplied to the temperature control unit in order to compensate for a temperature change in the reaction chamber caused by the flow of the raw material gas into the reaction chamber when the radicals are generated under the generation conditions is stored in association with the generation conditions; a measurement control unit that controls the operation of the power supply unit and the radical generation unit, and supplies the temperature control unit with power in an amount corresponding to the generation conditions stored in the memory unit during a period in which the radicals are introduced into the reaction chamber; a mass separation unit that separates product ions generated from the precursor ions in the reaction chamber according to their mass-to-charge ratios; an ion detector that detects ions separated by the mass separator; A mass spectrometer comprising:

6. The mass spectrometer of claim 5 , wherein the reaction chamber is a collision cell.

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