Quality analysis equipment

Abstract

An aspect of a mass spectrometer according to the present invention is a mass spectrometer that includes a measuring unit having an ion source (10) for ionizing a sample component, a mass separator (16) for separating ions according to m / z, an ion detector (17) for detecting separated ions, and one or more ion-transporting optical systems (12, 14) arranged between the ion source and the mass separator, said mass spectrometer having an auto-tuning function for optimizing values of a plurality of parameters related to the measuring unit, the mass spectrometer comprising: a necessity determination unit (32, 33) for determining whether or not auto-tuning of the plurality of parameters is necessary; and an auto-tuning execution unit (34) for controlling the measuring unit so as to exclude parameters for which the necessity determination unit has determined that auto-tuning is not necessary, and, regarding the parameters for which it has been determined that auto-tuning is necessary, execute mass spectroscopy while altering the values of said parameters, while adjusting the values of said parameters such that a result of the mass spectroscopy satisfies prescribed adjustment conditions.

Description

[Technical field]

[0001] The present invention relates to a mass spectrometer. [Background technology]

[0002] A mass spectrometer used as a detector for liquid chromatography (LC) has many ion optical elements, including a mass separator, between an ion source that ionizes components in a liquid sample and an ion detector that finally detects ions derived from the sample components. Therefore, the performance of a mass spectrometer, such as mass accuracy, resolution, and sensitivity, depends on the voltages applied to these various ion optical elements and ion detectors, and in order to achieve high performance, it is necessary to appropriately adjust the voltages applied to each of these components.

[0003] A typical mass spectrometer is provided with a function that allows a user to manually adjust the applied voltage, etc., while observing on a display screen the mass peaks obtained by mass spectrometry of a standard sample. However, such manual tuning work is not only cumbersome, but also limited to those who can perform it. For this reason, recent mass spectrometers are equipped with an auto-tuning function that automatically adjusts the voltages applied to multiple ion optical elements, ion detectors, etc., depending on the intensity of the mass peaks obtained by performing mass spectrometry on a standard sample, mass shifts, etc. (see Patent Documents 1 and 2, Non-Patent Document 1, etc.).

[0004] In the mass spectrometer described in Non-Patent Document 1, auto-tuning is started by the user clicking an "auto-tuning start" button provided in a specific display screen. Furthermore, according to the description in Non-Patent Document 1, the manufacturer recommends that auto-tuning be performed when maintenance has been performed on the inside of the device that involves stopping the vacuum, when the device is not working properly, or when the device has been stopped for a long period of time. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2018 / 116443 [Patent Document 2] International Publication No. 2020 / 054013 [Non-patent literature]

[0006] [Non-Patent Document 1] "Frequently Asked Questions (FAQ) (Q) LCMS Autotuning", [Online], [Searched September 28, 2021], Shimadzu Corporation, Internet <url: https: faq.an.shimadzu.co.jp faq show 3177?category_id="82&site_domain=default"> Summary of the Invention [Problem to be solved by the invention]

[0007] Autotuning performed in conventional mass spectrometers requires adjustment of parameters such as applied voltages in many components, and therefore takes a considerable amount of time from start to finish. Because the instrument cannot be used while autotuning is in progress, performing autotuning frequently increases the instrument's downtime and reduces operational efficiency. In addition, frequent autotuning increases the amount of consumables used, such as standard samples for adjustment and various gases (nebulizing gas, etc.), resulting in higher running costs. For these reasons, it is desirable to avoid unnecessary autotuning operations as much as possible.

[0008] As described above, in conventional devices, the decision of whether to perform auto-tuning and the timing of performing it are left to the operator, and the reality is that operators respond differently, for example, even if the device is in the same poor condition, one operator performs auto-tuning while another operator continues to use the device without performing auto-tuning. Therefore, auto-tuning is often performed even in situations where it is not actually necessary, which often results in a decrease in the operating efficiency of the device and an increase in running costs. Conversely, there are also cases where the device is in a state where auto-tuning is actually required, and by continuing to use the device as is, inaccurate analysis results are obtained.

[0009] As mentioned above, there must be some reason for performing auto-tuning. However, in conventional devices, although the fact that auto-tuning was performed is recorded in a log, the reason for performing it is not recorded. Therefore, there is a risk that the traceability of the device state may be incomplete. Also, it is difficult to verify the validity of performing auto-tuning later.

[0010] Furthermore, in order to avoid the variation in operator judgment regarding the implementation of auto-tuning as described above, it is necessary to strictly manage the implementation criteria for auto-tuning, but with conventional devices, it was difficult to manage such implementation criteria.

[0011] The present invention has been made to solve these problems, and one of its main objectives is to provide a mass spectrometer that can save time and consumables required for autotuning by avoiding the execution of unnecessary and wasteful autotuning. [Means for solving the problem]

[0012] One aspect of a mass spectrometer according to the present invention, which has been made to solve the above problems, is a mass spectrometer including a measurement unit having an ion source for ionizing sample components, a mass separator for separating ions according to their mass-to-charge ratio, an ion detector for detecting the separated ions, and one or more ion transport optical systems disposed between the ion source and the mass separator, the mass spectrometer having an autotuning function for optimizing values ​​of a plurality of parameters related to the measurement unit, a necessity determination unit that determines whether auto-tuning is necessary for the plurality of parameters; an auto-tuning execution unit that controls the measurement unit to execute mass spectrometry while changing the values ​​of parameters determined to require auto-tuning, excluding parameters determined by the necessity determination unit to not require auto-tuning, and adjusts the values ​​of the parameters so that the results of the mass spectrometry satisfy a predetermined adjustment condition; It is equipped with the following. Effect of the Invention

[0013] In the above-described aspect of the mass spectrometer according to the present invention, adjustment is automatically performed only on the parameter values ​​of the components for which the necessity determination unit has determined that autotuning is necessary, rather than on all of the multiple parameters. This makes it possible to avoid unnecessary autotuning that does not affect performance and is not required, thereby saving time and consumables required for autotuning. As a result, the downtime of the device can be reduced, enabling the device to be operated efficiently. Furthermore, the running costs of analysis can be reduced.

[0014] Furthermore, in the above-described aspect of the mass spectrometer according to the present invention, auto-tuning can be performed when the performance of the apparatus is degraded, without relying on the judgment of the operator. This reduces the workload of the operator, and prevents differences in the implementation status of auto-tuning due to individual differences in the experience, skill, etc. of the operator. Furthermore, by managing the judgment criteria in the necessity judgment unit as numerical values, the implementation conditions of auto-tuning can be quantitatively and accurately managed. [Brief description of the drawings]

[0015] [Figure 1] 1 is a schematic diagram of an embodiment of a mass spectrometer according to the present invention; [Diagram 2] 4 is a flowchart showing a general flow of an auto-tuning operation in the mass spectrometer of the present embodiment. [Diagram 3] 4 is a flowchart showing a specific example of an auto-tuning operation in the mass spectrometer of the present embodiment. [Figure 4] FIG. 4 shows an example of a system check item setting screen in the mass spectrometer of the present embodiment. [Diagram 5] FIG. 4 shows an example of a system check condition setting screen in the mass spectrometer of the present embodiment. [Figure 6] FIG. 2 is a diagram showing an example of the relationship between the ion guide voltage and the relative ion intensity in a mass spectrometer. [Figure 7] FIG. 4 is a diagram showing an example of the relationship between detector voltage and detector gain in a mass spectrometer. [Figure 8] FIG. 13 is a diagram showing an example of a state of a mass peak when adjusting the resolution and mass deviation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of a mass spectrometer according to the present invention will now be described with reference to the accompanying drawings, in which: Figure 1 is a schematic diagram of a single-type quadrupole mass spectrometer according to this embodiment.

[0017] As shown in Fig. 1, this mass spectrometer has an ionization chamber 2 that ionizes components (compounds) in a liquid sample under an atmosphere of approximately atmospheric pressure inside a chamber 1, and an analysis chamber 5 that is maintained in a high vacuum atmosphere for separating and detecting ions derived from sample components according to their mass-to-charge ratio (hereinafter sometimes referred to as "m / z"). Between the ionization chamber 2 and the analysis chamber 5, a first intermediate vacuum chamber 3 and a second intermediate vacuum chamber 4 are provided, in which the degree of vacuum is increased stepwise. The first intermediate vacuum chamber 3 is evacuated by a rotary pump (not shown), and the second intermediate vacuum chamber 4 and the analysis chamber 5 are evacuated by a combination of a rotary pump and a turbo molecular pump (not shown). That is, this mass spectrometer is configured as a multi-stage differential pumping system, whereby the analysis chamber 5 in the final stage can be maintained at a high degree of vacuum.

[0018] An ionization probe 10 that ionizes components in a sample by electrospray ionization (ESI) is disposed in the ionization chamber 2. The ionization chamber 2 and the first intermediate vacuum chamber 3 are in communication with each other through a desolvation tube 11 that is heated to a predetermined temperature. In the configuration of this example, the direction in which the ionization probe 10 sprays charged droplets and the direction in which the desolvation tube 11 sucks in ions are in a positional relationship that is approximately perpendicular to each other, but this does not necessarily have to be perpendicular. Also, instead of an ion source based on the ESI method, an ion source based on another ionization method, such as atmospheric pressure chemical ionization or atmospheric pressure photoionization, can be used.

[0019] A first ion guide 12 that converges and transports ions by the action of a high-frequency electric field is disposed in the first intermediate vacuum chamber 3. This first ion guide 12 is configured with four virtual rod electrodes arranged to surround the ion optical axis C, and each virtual rod electrode is composed of a plurality of electrodes divided along the direction of the ion optical axis C. The first intermediate vacuum chamber 3 and the second intermediate vacuum chamber 4 are communicated with each other through a minute ion passing hole 13a formed in the top of a substantially conical skimmer 13.

[0020] A second ion guide 14 that converges and transports ions by the action of a high-frequency electric field is disposed within the second intermediate vacuum chamber 4. This second ion guide 14 is made up of a plurality of (e.g., eight) rod electrodes arranged parallel to the ion optical axis C so as to surround the ion optical axis C. The second intermediate vacuum chamber 4 and the analysis chamber 5 are communicated with each other through a minute ion passing hole 15.

[0021] A quadrupole mass filter 16 serving as a mass separator, and an ion detector 17 are installed in the analysis chamber 5. The quadrupole mass filter 16 is made up of a main filter 161 and a prefilter 162. The main filter 161 is configured with four rod electrodes extending parallel to the ion optical axis C and arranged around the ion optical axis C. The prefilter 162 is also made up of four rod electrodes that are shorter than the rod electrodes that make up the main filter 161. The ion detector 17 is made up of, for example, a conversion dynode and a secondary electron multiplier. A detection signal from the ion detector 17 is input to a data processing unit 20.

[0022] A DC voltage or a voltage obtained by adding a DC voltage and an RF voltage is applied from a voltage generating unit 18 to the ionization probe 10, the desolvation tube 11, the first ion guide 12, the skimmer 13, the second ion guide 14, the pre-filter 162 and the main filter 161 of the quadrupole mass filter 16, the ion detector 17, and the like. However, in order to avoid the drawing becoming complicated, only some of the voltage supply lines are drawn in FIG. 1. As an example of a specific applied voltage, a voltage obtained by adding a DC bias voltage to an RF voltage for forming an RF electric field for converging ions is applied to each of the first ion guide 12 and the second ion guide 14. A voltage obtained by adding a DC bias voltage to an RF voltage and a DC voltage for forming a quadrupole electric field for separating ions according to m / z is applied to the main filter 161 of the quadrupole mass filter 16. Furthermore, a voltage obtained by adding a DC bias voltage to the RF voltage applied to the main filter 161 is applied to the pre-filter 162 of the quadrupole mass filter 16 .

[0023] The voltage generating unit 18 is controlled by a control unit 30. The control unit 30 includes, as functional blocks, an analysis control unit 31, a system check control unit 32, a check result determination unit 33, an auto-tuning control unit 34, a tuning information storage unit 35, a report creation unit 36, and a tuning condition setting reception unit 37. In addition, an input unit 40 and a display unit 41 serving as a user interface are connected to the control unit 30.

[0024] In general, the data processing unit 20 and the control unit 30 are implemented as hardware in the form of a personal computer including a CPU, memory, etc., or a more powerful computer called a workstation, and at least a part of their functions are realized by executing dedicated processing and control software (computer program) preinstalled on the computer. In this case, the input unit 40 is a pointing device such as a keyboard or a mouse attached to the computer, and the display unit 41 is a display monitor attached to the computer.

[0025] The computer program can be provided to the user by being stored in a computer-readable non-transitory recording medium, such as a CD-ROM, a DVD-ROM, a memory card, or a USB memory (dongle). The program can also be provided to the user in the form of data transfer via a communication line such as the Internet. Furthermore, the program can be pre-installed in a computer that is a part of the system (strictly speaking, a storage device that is a part of the computer) when the user purchases the system.

[0026] In the mass spectrometer of this embodiment, a normal mass analysis operation performed under the control of the analysis control unit 31 will be briefly described.

[0027] During normal analysis, when a liquid sample eluted from a column of a liquid chromatograph (LC) (not shown) is introduced into the ionization probe 10, an electric charge is imparted to the liquid sample at the tip of the ionization probe 10, and the liquid sample is sprayed into the ionization chamber 2 as minute charged droplets. In the process in which the solvent in the sprayed charged droplets evaporates and the charged droplets are made finer, the sample components in the droplets are ionized. The ions generated in the ionization chamber 2, together with the fine charged droplets, are sucked into the desolvation tube 11 by a gas flow formed by the pressure difference between both ends of the desolvation tube 11. Even while the fine charged droplets pass through the desolvation tube 11, evaporation of the solvent is promoted, and the generation of ions progresses.

[0028] The ions that entered the first intermediate vacuum chamber 3 progress while being captured by the RF electric field formed by the first ion guide 12, and are sent through the ion passing hole 13a to the second intermediate vacuum chamber 4. The ions that entered the second intermediate vacuum chamber 4 progress while being converged by the RF electric field formed by the second ion guide 14, and are sent through the ion passing hole 15 to the analysis chamber 5.

[0029] In the analysis chamber 5, ions are introduced into the main filter 161 through the pre-filter 162. A voltage obtained by superimposing an RF voltage on a DC voltage is applied to each rod electrode of the main filter 161, and only ions having a specific m / z corresponding to the voltage pass through the main filter 161 and reach the ion detector 17. The ion detector 17 generates an ion intensity signal corresponding to the amount of ions that have reached it, and sends this signal to the data processing unit 20. By changing the DC voltage and the RF voltage applied to each rod electrode of the main filter 161 while maintaining a predetermined relationship, the m / z of ions that can pass through the main filter 161 changes. As a result, for example, a scan over a predetermined m / z range is performed, and the data processing unit 20 can create a mass spectrum showing the change in the ion intensity signal over that m / z range.

[0030] Next, a characteristic auto-tuning operation executed in the mass spectrometer of this embodiment will be described. Fig. 2 is a flow chart showing a general flow of the auto-tuning operation. Fig. 3 is a flow chart showing a specific example of the auto-tuning operation. A user (an operator or an apparatus manager) sets in advance the conditions for performing auto-tuning using the results of a system check as follows (step S1).

[0031] Fig. 4 is a diagram showing an example of a system check item setting screen 50. Fig. 5 is a diagram showing an example of a system check condition setting screen 60. When the user performs a predetermined operation on the input unit 40, the tuning condition setting receiving unit 37 displays a system check item setting screen 50 on the display unit 41, as exemplified in Fig. 4. In this example, the system check item setting screen 50 has a final state display area 51 and a condition setting area 52 arranged therein, and in the condition setting area 52, a check target selection area 53, a check item selection area 54, and an auto-tuning implementation condition selection area 55 as well as a plurality of instruction buttons including an "Execute" button 56 and a "Details" button 57 are arranged.

[0032] The final status display area 51 displays the execution date and time of the most recent system check and the results of that check.

[0033] Check target selection area 53 is provided with three selectable targets: consumables check, MS check, and detailed report (multiple selections are possible). When wishing to carry out a system check related to mass spectrometry as described below, the operator uses input unit 40 to check the check box corresponding to "MS check," as shown in FIG. 4. When wishing to confirm a detailed report related to the system check, the operator also checks the check box corresponding to "detailed report." By checking the "consumables check" check box, the remaining amount of consumables, such as inert gas for the nebulizing gas used in mass spectrometry, can be checked.

[0034] In the check item selection area 54, check items that can be checked by the system are provided so that they can be selected (multiple selections are possible). Of the five check items, three, "mass axis deviation," "half width," and "intensity," are related to whether autotuning is required. Here, mass axis deviation refers to mass accuracy, half width refers to the half width of the mass peak and represents resolution, and intensity refers to ion intensity and represents sensitivity.

[0035] The auto-tuning implementation condition selection area 55 provides three options for the conditions for performing auto-tuning, and if the operator wishes to perform auto-tuning depending on the results of the system check, he / she selects "Perform if any of mass axis deviation, half-width, or intensity fails" (hereinafter simply referred to as "Perform if fails") as shown in FIG. 4. If the operator wishes to perform auto-tuning after the system check regardless of the results of the system check, he / she selects "Perform always". If the operator wishes to perform only a system check without performing auto-tuning, he / she selects "Do not perform".

[0036] The "Execute" button 56 is a button for issuing an instruction to execute a system check. The "Details" button 57 is a button for transitioning to a screen for setting pass / fail criteria for each check item of the system check. When the "Details" button 57 is clicked while "Execute if Fail" is selected in the auto-tuning execution condition selection area 55, the tuning condition setting receiving unit 37 responds by displaying a system check condition setting screen 60, an example of which is shown in FIG.

[0037] The system check condition setting screen 60 has a pass / fail criteria input area 61 in which text boxes are arranged for inputting reference values ​​for judging each of the check items, "mass axis deviation," "half width," and "strength," to pass or fail. Default values ​​are determined for each of these reference values, and when an "Initialize" button 62 arranged below is clicked, the numerical values ​​in each text box in the pass / fail criteria input area 61 are changed to the default values. On the other hand, when an "OK" button 63 is clicked, the tuning condition setting receiving unit 37 responds by determining the numerical values ​​input in each text box at that time as the reference values ​​and sends them to the check result determining unit 33.

[0038] For example, when the operator makes settings on the system check item setting screen 50 and the system check condition setting screen 60 as shown in Figures 4 and 5, respectively, and then clicks the "Execute" button 56 on the system check item setting screen 50, the tuning condition setting acceptance unit 37 instructs the system check control unit 32 to execute a system check. In response, the system check control unit 32 executes a system check as follows (step S2).

[0039] Specifically, the system check control unit 32 supplies a standard sample (sample components such as polyethylene glycol (PEG) or polypropylene glycol (PPG)) from a standard sample supply unit (not shown) to the ionization probe 10 instead of the eluate from the LC, and operates each unit to perform a scan measurement over a predetermined m / z range under preset measurement conditions. The data processing unit 20 creates a mass spectrum in which mass peaks corresponding to the sample components are observed based on the ion intensity signal obtained by the scan measurement. Here, the preset measurement conditions can be parameter values ​​based on the results of auto-tuning if auto-tuning has been performed in the past.

[0040] The check result determination unit 33 receives the created mass spectrum and checks whether any check items have failed by determining whether the intensities, mass axis shift, and half-widths of mass peaks observed near a predetermined number of m / z values ​​meet the respective standard values ​​set on the system check condition setting screen 60 (step S3). If all check items meet the standard values ​​(No in step S3), there is no need for auto-tuning, and the process ends. When the process ends, a display indicating that there are no problems in the system check may be output to the display unit 41.

[0041] On the other hand, if there is even one failed check item, the process proceeds from step S3 to step S4, where the auto-tuning control unit 34 excludes the components corresponding to the passed check items from the targets of auto-tuning, and performs auto-tuning on the components corresponding to the failed check items. In this example, auto-tuning is performed, for example, according to the procedure shown in Fig. 3. The check items and the parameters of the components to be subjected to auto-tuning are associated in advance.

[0042] First, if the check item "strength" fails (No in step S10), the autotuning controller 34 first optimizes the voltages applied to the first ion guide 12 and the second ion guide 14 (step S11). This is because when the ion strength is low, the ion transmission rate in the first ion guide 12 and / or the second ion guide 14 is low, and a sufficient amount of ions are often not supplied to the quadrupole mass filter 16.

[0043] At this time, the autotuning control unit 34 controls the voltage generating unit 18 to set the value of the voltage applied to the components other than the first ion guide 12 or the second ion guide 14 to be tuned to a specified voltage. Then, the voltage generating unit 18 controls each unit to perform mass analysis on the standard sample at each voltage value while sequentially changing the value of the voltage (DC voltage) applied to the first ion guide 12 or the second ion guide 14 over a predetermined voltage range with a predetermined step width. As a result, the data processing unit 20 determines the ion intensities of the components contained in the standard sample at each different ion guide voltage. The ion intensities are ion intensities at a plurality of specific m / z values.

[0044] FIG. 6 is a diagram showing an example of the relationship between the ion guide voltage and the relative ion intensity. Although there is some variation between devices, when the ion guide voltage is changed, the ion intensity fluctuates in a mountain shape, and the fluctuation depends on m / z. Therefore, the autotuning control unit 34 searches for an ion guide voltage that maximizes or is close to the maximum ion intensity for each m / z value from the ion intensity data obtained by changing the ion guide voltage in multiple steps. The ion guide voltage for each m / z value thus obtained is stored in the tuning information storage unit 35 as the optimal parameter value of the ion guide voltage. Similar tuning may be performed for each of the first ion guide 12 and the second ion guide 14.

[0045] Next, with the ion guide voltage set to the above-mentioned optimum parameter value, the autotuning control unit 34 adjusts the voltage (detector voltage) applied to the ion detector 17 so that the gain of the ion detector 17 becomes a predetermined value (step S12). Fig. 7 is a diagram showing an example of the relationship between the detector voltage and the detector gain. By appropriately determining the detector gain in this way, it is possible to reduce saturation of the output of the ion detector 17 even when the amount of components is large during actual analysis.

[0046] Next, if the "half width", which is one of the check items, i.e., the resolution, fails (No in step S13), the autotuning control unit 34 adjusts the ratio of the DC voltage (voltage value) and the RF voltage (amplitude value) applied to the main filter 161 of the quadrupole mass filter 16 (step S14). Specifically, for each of a plurality of m / z values ​​obtained by mass spectrometry of a standard sample, a mass peak 71 as shown in FIG. 8 is obtained. Since the peak width of this mass peak corresponds to the resolution, the ratio of the DC voltage and the RF voltage is adjusted so that the peak width becomes a predetermined target value (for example, 0.7 u). The ratio of the DC voltage and the RF voltage for each m / z value thus obtained is stored in the tuning information storage unit 35 as an optimal parameter value. Since adjusting the ratio of the DC voltage and the RF voltage changes not only the half width but also the mass axis, the process proceeds to step S16 described later after the end of step S14.

[0047] Even if the "half width" is passed in step S13, if the "mass axis offset", which is one of the check items, i.e., the mass accuracy, is not passed (No in step S15), the autotuning control unit 34 adjusts the magnitude of the DC voltage while maintaining the ratio of the DC voltage and the RF voltage applied to the main filter 161 of the quadrupole mass filter 16 (step S16). Specifically, for each different m / z, the value of the DC voltage is adjusted so that, for a mass peak 71 as shown in FIG. 8, an m / z marker 72 indicating a centroid peak determined from the mass peak 71 is positioned at the position of the theoretical m / z value 73 in the center of the screen 70. The DC voltage value for each m / z thus determined is stored in the tuning information storage unit 35 as an optimal parameter value.

[0048] In this manner, when any one of the three check items, intensity (sensitivity), half-width (resolution), and mass axis shift (mass accuracy), fails, the auto-tuning control unit 34 automatically performs tuning on the components that mainly affect the failed check item, and can store optimal parameter values ​​in the tuning information storage unit 35. Conversely, when any one of the three check items passes, tuning is not performed on the components corresponding to the passed check item (however, in the above example, when the half-width fails, the parameter corresponding to the mass axis shift is also tuned after tuning the parameter corresponding to the half-width).

[0049] After auto-tuning is completed, the system check control unit 32 executes a system check similar to that in step 2 again using the optimal parameter values ​​stored in the tuning information storage unit 35, and stores the mass analysis results (step S5). If creation of a "detailed report" is selected in the check target selection area 53 as described above, the report creation unit 36 ​​creates a detailed report including the mass spectrum acquired during the system check before auto-tuning was performed, the mass spectrum acquired during the system check after auto-tuning was performed, and the parameter values ​​at the time of these executions, and stores the detailed report in a predetermined storage unit and displays it on the display unit 41 (step S6).

[0050] By saving such detailed reports, the equipment status before and after auto-tuning can be easily confirmed, and for example, it is possible to verify later whether auto-tuning was performed properly or not. It is also possible to confirm the equipment status when auto-tuning was performed, and from there, it is possible to understand the reason why auto-tuning was performed (which system item failed and with what value).

[0051] In the above description of the mass spectrometer of the embodiment, only the parameter values ​​of the components that have the greatest effect on the three types of performance, namely, intensity (sensitivity), resolution, and mass accuracy, are adjusted by autotuning, but parameter values ​​of other components that similarly affect performance may also be adjusted. For example, when the intensity is low, it is often the case that ionization in the ion source is not performed properly, so it is possible to adjust the voltage applied to the ionization probe 10. Also, items other than the three check items of intensity, half-width, and mass axis deviation may be added to the system check judgment.

[0052] In the above description, only the voltage applied to the ion optical element and the like is the subject of auto-tuning, but elements other than voltage, such as temperature and gas flow rate, may also be subject to auto-tuning.

[0053] Furthermore, although the mass spectrometer in the above embodiment is a single-type quadrupole mass spectrometer, it is of course possible to apply the present invention to a triple quadrupole mass spectrometer, a quadrupole time-of-flight (Q-TOF) mass spectrometer, or the like. It is also of course possible to apply the present invention to a mass spectrometer that ionizes components in a sample gas and performs mass analysis, not on the premise that it is connected to an LC, but on the premise that it is connected to a gas chromatograph. It is also of course possible that the components that are the targets of auto-tuning change depending on the configuration of the mass spectrometer.

[0054] Furthermore, the above-described embodiment and the above-described modified examples are merely examples of the present invention, and it is clear that any appropriate modifications, additions, and amendments made within the spirit of the present invention will also be encompassed within the scope of the claims of the present application.

[0055] [Various aspects] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0056] (Item 1) One aspect of the mass spectrometer according to the present invention is a mass spectrometer including a measurement unit having an ion source for ionizing sample components, a mass separator for separating ions according to their mass-to-charge ratio, an ion detector for detecting the separated ions, and one or more ion transport optical systems disposed between the ion source and the mass separator, the mass spectrometer having an autotuning function for optimizing values ​​of a plurality of parameters related to the measurement unit, a necessity determination unit that determines whether auto-tuning is necessary for the plurality of parameters; an auto-tuning execution unit that controls the measurement unit to execute mass spectrometry while changing the values ​​of parameters determined to require auto-tuning, except for parameters determined by the necessity determination unit to not require auto-tuning, and adjusts the values ​​of the parameters so that the results of the mass spectrometry satisfy a predetermined adjustment condition; It is equipped with the following.

[0057] In the mass spectrometer described in item 1, the parameter is typically an applied voltage, but may also be a gas flow rate, gas pressure, temperature, etc.

[0058] In the mass spectrometer described in paragraph 1, adjustment is automatically performed only on the parameter values ​​of components that are determined by the necessity determination unit to require autotuning, rather than on all of the multiple parameters. This makes it possible to avoid unnecessary execution of autotuning that does not affect performance and is not required, thereby saving time and consumables required for autotuning. As a result, downtime of the device can be reduced, enabling the device to be operated efficiently. In addition, the running costs of analysis can be reduced.

[0059] Furthermore, in the mass spectrometer described in paragraph 1, auto-tuning can be performed when the performance of the device is degraded, without relying on the judgment of the operator. This reduces the workload of the operator and avoids a situation in which differences in the implementation status of auto-tuning occur due to individual differences in the operator's experience, skill, etc. Furthermore, by managing the judgment criteria in the necessity judgment unit as numerical values, the implementation conditions of auto-tuning can be quantitatively and accurately managed.

[0060] (2) In the mass spectrometer according to the first aspect, the necessity determining unit is a system check execution unit that controls the measurement unit to perform mass spectrometry on a predetermined sample under preset parameter values ​​and obtains mass spectrometry results corresponding to a plurality of check items; a check result determination unit that determines whether or not a mass spectrometry result obtained by the system check execution unit satisfies a predetermined pass / fail condition for each of the plurality of check items; It may include:

[0061] In the mass spectrometer described in paragraph 2, the system check execution unit can perform a system check for predetermined check items, for example, when the apparatus is started up (started up), every time a predetermined time has elapsed (i.e., periodically), or in response to an instruction from a user. According to the analyzer described in paragraph 2, the results of such a system check can be used to perform appropriate tuning only for parameters of necessary components when necessary. The time required for the system check itself is sufficiently shorter than autotuning, and analysis can be performed in good apparatus condition without performing unnecessary tuning.

[0062] (Item 3) In the mass spectrometer according to item 1 or 2, the check items can include at least one of sensitivity, mass axis shift, and half-width of a mass peak.

[0063] Preferably, the check items include all of sensitivity, mass axis shift, and half-width. According to the mass spectrometer described in paragraph 3, the parameters of the device related to important performance in mass spectrometry can be appropriately set to ensure sufficient performance.

[0064] (Item 4) In the mass spectrometer described in any one of Items 1 to 3, the check items can include sensitivity, and the auto-tuning execution unit can adjust a voltage applied to at least one of the ion transport optical systems if the sensitivity fails.

[0065] The ion transport optical system referred to here is, for example, an ion guide (including an ion funnel), an ion lens, an ion deflector, etc. The ion transport optical system arranged between the ion source and the mass separator plays an important role in transporting ions originating from sample components generated in the ion source to the mass separator, and a large loss of ions during this transport leads to a decrease in sensitivity. According to the mass spectrometer described in paragraph 4, the voltage applied to this ion transport optical system is appropriately adjusted, so that high sensitivity can be achieved.

[0066] (Item 5) In the mass spectrometer described in any one of Items 1 to 4, the check items can include sensitivity, and if the sensitivity fails, the auto-tuning execution unit can adjust the gain by adjusting the voltage applied to the ion detector.

[0067] Generally, increasing the voltage applied to an ion detector increases the detector gain, but if the gain is too high, there is a high possibility that the output will become saturated when a large number of ions are incident on the ion detector. In contrast, according to the mass spectrometer described in paragraph 5, the detector gain is appropriately adjusted, so that output saturation can be avoided even when a large number of ions are incident on the ion detector.

[0068] (Item 6) In the mass spectrometer described in any one of Items 1 to 5, the mass separator can be a quadrupole mass filter, the check items can include a half-width of a mass peak, and the auto-tuning execution unit can adjust the ratio of the DC voltage and the RF voltage applied to the quadrupole mass filter if the half-width fails.

[0069] (Item 7) In the mass spectrometer described in any one of Items 1 to 6, the mass separator can be a quadrupole mass filter, the check items can include mass axis misalignment, and the auto-tuning execution unit can adjust the magnitude of the RF voltage applied to the quadrupole mass filter if the mass axis misalignment fails.

[0070] According to the mass spectrometer described in paragraphs 6 and / or 7, the parameters of the device related to resolution and / or mass accuracy, which are important performance characteristics in mass spectrometry, can be appropriately set to ensure sufficient performance.

[0071] (Item 8) The mass spectrometer according to any one of items 1 to 7, a recording unit for recording the mass spectrometry results and the parameter settings thereof before and after the autotuning is performed; an output unit that displays or prints out the information recorded by the recording unit in response to an operation by a user; The present invention may further include the following.

[0072] According to the mass spectrometer described in paragraph 8, the state of the apparatus before and after autotuning is performed is recorded, so that it is possible to verify at a later date whether or not the autotuning was performed appropriately.

[0073] (Item 9) The mass spectrometer according to any one of items 1 to 8 may further include an information receiving unit that receives input of a judgment threshold value, which is a pass / fail condition for the plurality of check items, by a user.

[0074] According to the mass spectrometer described in paragraph 9, the user can establish and manage the implementation criteria for autotuning based on the results of the system check. [Explanation of symbols]

[0075] 1. Chamber 2…Ionization chamber 3...First intermediate vacuum chamber 4...Second intermediate vacuum chamber 5…Analysis room 10…Ionization probe 11...Desolvation tube 12…First ion guide 13. Skimmer 13a...Ion passage hole 14…Second ion guide 15...Ion passage hole 16...Quadrupole mass filter 161…Main filter 162…Pre-filter 17…Ion detector 18...Voltage generating section 20...Data processing unit 30...Control section 31...Analysis control section 32...System check control section 33...Check result judgment section 34...Auto-tuning control unit 35…Tuning information storage section 36…Report Writing Department 37…Tuning condition setting reception section 40...Input section 41...Display section C…Ion optical axis< / url:>

Claims

1. A mass spectrometer including, as components, a measurement unit having an ion source for ionizing sample components, a mass separator for separating ions according to their mass-to-charge ratios, an ion detector for detecting the separated ions, and one or more ion transport optical systems disposed between the ion source and the mass separator, and having an autotuning function for optimizing parameter values ​​of a plurality of components among the components, a system check execution unit that controls the measurement unit to perform mass spectrometry on a standard sample under predetermined parameter values ​​prior to the execution of auto-tuning, and obtains information corresponding to a plurality of check items including at least one of sensitivity, mass resolution, and mass accuracy from the results of the mass spectrometry; a check result determination unit that determines whether or not information corresponding to the plurality of check items obtained by the system check execution unit satisfies a predetermined pass / fail condition, and, when it is determined that the information has failed, identifies a component that requires auto-tuning from the failed check items; and an auto-tuning execution unit that controls the measurement unit to execute mass spectrometry on a standard sample while changing the values ​​of the parameters of the components identified by the check result determination unit as requiring auto-tuning, and adjusts the values ​​of the parameters so that the results of the mass spectrometry satisfy a predetermined adjustment condition; A mass spectrometer comprising:

2. 2. The mass spectrometer according to claim 1, wherein the check items include sensitivity, and the autotuning execution unit adjusts a voltage applied to at least one of the ion transport optical systems when the sensitivity fails.

3. 2. The mass spectrometer according to claim 1, wherein the check items include sensitivity, and when the sensitivity fails, the auto-tuning execution unit adjusts a gain by adjusting a voltage applied to the ion detector.

4. 2. The mass spectrometer of claim 1, wherein the mass separator is a quadrupole mass filter, the check items include a mass resolution indicated by a half-width of a mass peak, and the auto-tuning execution unit adjusts a ratio of a DC voltage and an RF voltage applied to the quadrupole mass filter when the half-width fails.

5. 2. The mass spectrometer of claim 1, wherein the mass separator is a quadrupole mass filter, the check items include mass accuracy indicated by a mass axis misalignment, and the autotuning execution unit adjusts a magnitude of an RF voltage applied to the quadrupole mass filter when the mass axis misalignment fails.

6. a recording unit for recording the mass spectrometry results and the parameter settings thereof before and after the autotuning is performed; an output unit that displays or prints out the information recorded by the recording unit in response to an operation by a user; The mass spectrometer of claim 1 further comprising:

7. The mass spectrometer according to claim 1 , further comprising an information receiving unit that receives input of a decision threshold that is a pass / fail condition for the plurality of check items by a user.

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