JP5454416B2 - Mass spectrometer - Google Patents

Description

  The present invention relates to a mass spectrometer, and more particularly to an abnormality detection technique for detecting an abnormality that occurs during analysis using a mass spectrometer.

  In mass spectrometers, mass analyzers that separate sample-derived ions according to mass-to-charge ratio and detectors that detect ions are placed in an analysis chamber that is evacuated by a high-performance vacuum pump such as a turbomolecular pump. Has been. In general, if the analysis is performed in a state where the degree of vacuum in the analysis chamber is not sufficiently increased, the analysis cannot be performed with sufficient sensitivity and accuracy, and it may cause contamination of the mass analyzer and the detector. Therefore, in the conventional mass spectrometer, a vacuum gauge such as an ion gauge for monitoring the degree of vacuum is attached to the analysis chamber, and the monitor value of the degree of vacuum (pressure) by this vacuum gauge is displayed on the display. (Refer to patent document 1 etc.). When the analysis is performed, the analyst can check the displayed value, and if the gas pressure is higher than a certain threshold value, it can be determined that the evacuation is still insufficient and the analysis is not performed. In addition, in the mass spectrometer described in Patent Document 1, control is performed such that an abnormality notification that alerts the analyst is performed when the degree of vacuum decreases during analysis.

  Further, in a mass spectrometer using an atmospheric pressure ion source such as an electrospray ion source, one or more intermediate vacuum chambers are arranged between an ionization chamber that is a substantially atmospheric pressure atmosphere and an analysis chamber that is a high vacuum atmosphere. A multi-stage differential exhaust system configuration is employed. In such a mass spectrometer, not only the analysis chamber, but also a vacuum gauge such as a Pirani gauge is installed in an intermediate vacuum chamber that is evacuated by a rotary pump, for example, and the vacuum value in the intermediate vacuum chamber is monitored. Is also displayed on the display. Therefore, the analyst can confirm the degree of vacuum in the intermediate vacuum chamber in addition to the degree of vacuum in the analysis chamber, and perform the analysis in a state where a sufficient degree of vacuum is secured.

  As described above, in the conventional mass spectrometer, it is possible to avoid performing an inappropriate analysis in a state where the degree of vacuum is lower than the target state by monitoring the degree of vacuum in the intermediate vacuum chamber or the analysis chamber. It has various functions. However, even if the degree of vacuum in the intermediate vacuum chamber or the analysis chamber is sufficiently high, the expected signal intensity may not be obtained, and the analysis sensitivity and accuracy may be low. Of course, there are various reasons why a sufficient signal intensity cannot be obtained in the mass spectrometer, but it may be caused by the following problems of the apparatus.

  (1) In an atmospheric pressure ionization mass spectrometer using a multistage differential exhaust system, in order to ensure a higher degree of vacuum in the room, a small-diameter ion introduction part (such as a heating capillary or skimmer) is used. A configuration for transporting ions to the next stage is adopted. In such an ion introduction part, a droplet with insufficient solvent vaporization may jump in, and the ion introduction part is relatively easily clogged. When the ion introduction part is clogged, it becomes impossible to transport ions to the next stage, and the signal intensity of the ions finally detected decreases.

  (2) In an MS / MS mass spectrometer that uses a collision cell to dissociate ions by collision-induced dissociation (CID), gas leakage occurs in a pipe that supplies CID gas such as argon into the collision cell. If the CID gas cannot be sufficiently supplied due to an abnormality in the operation of the gas supply valve, product ions are hardly generated in the collision cell. Then, no matter how much precursor ions are introduced into the collision cell, the signal intensity of the product ions that are finally detected decreases.

JP 2000-36283 A

  The present invention was made in order to solve the above-mentioned problems, and the object of the present invention is to automatically check in the analysis for problems mainly due to the above-described problems of the apparatus or the lack of maintenance, An object of the present invention is to provide a mass spectrometer capable of performing analysis in a good state.

The present invention, which has been made to solve the above problems, holds a vacuum chamber that is evacuated and a gas that is communicated with the vacuum chamber and that is supplied from the outside in order to perform a predetermined operation on ions before mass analysis. An operation region that is disposed in the vacuum chamber, and a mass analyzer that separates ions after being manipulated in the operation region according to a mass-to-charge ratio and a detector that detects the separated ions. In the mass spectrometer to
a) pressure detecting means for detecting a gas pressure inside the vacuum chamber;
b) an abnormality determining unit that determines that the gas supply to the operation region is abnormal when the gas pressure detected by the pressure detecting unit before execution of the analysis is equal to or lower than a predetermined threshold;
It is characterized by having.

In a typical aspect of the present invention, the operation region is a collision cell disposed in the vacuum chamber to dissociate ions by colliding ions with a predetermined gas, and the mass analyzer includes the collision A mass analyzer in a subsequent stage that separates product ions generated in the cell according to a mass-to-charge ratio, and the precursor ion having a specific mass-to-charge ratio is selected from various ions before the collision cell. It can be set as the structure further equipped with the mass spectrometer of the front | former stage sent to a cell.

  In another aspect, the operation region may be a region in which ions are cooled and temporarily held by colliding ions with a predetermined gas.

  For example, in the mass spectrometer according to the above typical embodiment, when a predetermined gas is supplied to the collision cell and the gas is filled to a certain extent, the gas in the vacuum chamber is affected by the gas flowing out from the cell. The pressure tends to increase. On the other hand, when some trouble occurs in the gas supply to the collision cell, the amount of gas flowing out from the cell into the vacuum chamber is reduced, and the gas pressure in the vacuum chamber is relatively lowered. The abnormality determining means receives the detected value of the gas pressure in the vacuum chamber by the pressure detecting means before executing the analysis, and determines whether or not the detected value is equal to or less than a predetermined threshold value. If the gas pressure detection value is equal to or lower than the threshold value, that is, too low, it is determined that there is an abnormality in the gas supply to the collision cell, and alerting is performed by, for example, display or sound. Thus, the analyst can confirm the part related to the gas supply to the collision cell, and can quickly take appropriate measures such as repairing the apparatus and replenishing the gas.

In the present invention, the threshold value for determining the gas pressure detected by the pressure detection means may be a value predetermined by the device manufacturer or the like, or may be a value set by a user input.

According to the mass spectrometer according to the present invention, for example, a gas leak in a pipeline supplying CID gas into the collision cell, an abnormal operation of the gas supply valve, or an apparatus abnormality such as a gas exhaustion is automatically checked before analysis. Is done. As a result, it is possible to prevent the analysis from being performed while the apparatus is in an abnormal state, and collecting inappropriate data unnecessarily. In addition, it is possible to quickly take measures for eliminating the apparatus abnormality as described above.

1 is an overall configuration diagram of an MS / MS mass spectrometer according to an embodiment of the present invention. The flowchart which shows the control procedure of the system check in the MS / MS type | mold mass spectrometer by a present Example.

  Hereinafter, an MS / MS mass spectrometer which is an embodiment of the present invention will be described with reference to the accompanying drawings. FIG. 1 is an overall configuration diagram of an MS / MS type atmospheric pressure ionization mass spectrometer of this embodiment.

  In FIG. 1, a rotary pump 21 evacuates to a low vacuum atmosphere between an ionization chamber 1 that is an atmosphere of substantially atmospheric pressure and an analysis chamber 10 that is evacuated to a high vacuum atmosphere by a high-performance turbo molecular pump 23. The first intermediate vacuum chamber 4 and the second intermediate vacuum chamber 7 evacuated to a medium vacuum atmosphere by another turbo molecular pump 22 are provided, and the degree of vacuum increases stepwise in the direction in which ions travel (the gas pressure increases). Multi-stage differential exhaust system configuration. A liquid sample containing a sample component is sprayed into the ionization chamber 1 while being charged from the electrospray nozzle 2. The sprayed charged droplets are brought into contact with the surrounding atmosphere and are refined, and sample components are ionized in the process of evaporation of the solvent. Instead of electrospray ionization, ionization by other atmospheric pressure ionization methods such as atmospheric pressure chemical ionization and atmospheric pressure photoionization may be performed.

  The ionization chamber 1 and the first intermediate vacuum chamber 4 communicate with each other via a small-diameter heating capillary (corresponding to an ion introduction portion in the present invention) 3, and ions generated in the ionization chamber 1 are heated. The capillary 3 is sucked into the inside of the heating capillary 3 due to the differential pressure at both open ends. Then, the ions are discharged into the first intermediate vacuum chamber 4 together with the gas flow including the atmosphere and vaporized solvent flowing from the ionization chamber 1 into the first intermediate vacuum chamber 4. A first ion guide 5 for focusing ions by a high frequency electric field is disposed in the first intermediate vacuum chamber 4, and ions discharged from the outlet end of the heating capillary 3 are converged by the first ion guide 5 to be skimmer 6. The second intermediate vacuum chamber 7 is fed through an orifice formed at the top of the first vacuum chamber 7. In this example, the first ion guide 5 has a configuration in which four virtual rod electrodes composed of a plurality of electrode plates arranged in the direction of the ion optical axis C are arranged in parallel so as to surround the ion optical axis C. However, the configuration of the first ion guide 5 is not limited to this.

  In the second intermediate vacuum chamber 7, an octopole-type second ion guide 8 in which eight rod electrodes are arranged around the ion optical axis C is provided, and is formed by the second ion guide 8. The ions are sent to the analysis chamber 10 through the ion passage hole 9 by the action of the high frequency electric field. The configuration of the second ion guide 8 is not limited to that shown in FIG.

  A so-called triple quadrupole mass spectrometer is arranged in the analysis chamber 10. That is, between the first stage quadrupole mass filter (corresponding to the former mass analyzer in the present invention) 11 and the third stage quadrupole mass filter (corresponding to the latter mass analyzer in the present invention) 16, A collision cell 12 is disposed to dissociate the precursor ions to generate various product ions, and a second stage quadrupole 13 having no function of mass separation is disposed therein. The collision cell 12 is almost entirely sealed except for an ion incident hole and an ion emission hole provided on the ion optical axis C, and CID gas is externally supplied through a gas supply pipe 14 provided with a gas supply valve 15 in the middle. Is to be supplied. Furthermore, a detector 17 for detecting ions that arrive is disposed on the outlet side of the third-stage quadrupole mass filter 16. The detection signal from the detector 17 is input to the data processing unit 20, and the data processing unit 20 creates a mass spectrum or the like based on the detection signal obtained at the time of analysis.

  A first vacuum gauge 31 that detects the degree of vacuum (gas pressure) is installed in the first intermediate vacuum chamber 4, while a second vacuum gauge 32 that also detects the degree of vacuum (gas pressure) is installed in the analysis chamber 10. The pressure values detected by both vacuum gauges 31 and 32 are both input to the gas pressure determination unit 34 of the control unit 33. For example, a Pirani gauge may be used as the first vacuum gauge 31 for measuring the degree of vacuum in the low vacuum state, and an ion gauge may be used as the second vacuum gauge 32 for measuring the degree of vacuum in the high vacuum state. A display unit 35 and an input unit 36 are connected to a control unit 33 composed of a CPU or the like, and this control unit 33 has a function of controlling each unit during analysis.

An operation of a typical MS / MS analysis in the mass spectrometer of this embodiment will be schematically described.
The liquid sample containing the sample component to be analyzed is charged and sprayed from the electrospray nozzle 2 into the ionization chamber 1, and the ions generated thereby are carried into the first intermediate vacuum chamber 4 through the heating capillary 3. Furthermore, ions are sent to the second intermediate vacuum chamber 7 and the analysis chamber 10 and to a region with a high degree of vacuum by the action of the electric field by the first and second ion guides 5 and 8 . In the analysis chamber 10, ions are introduced into the space in the long axis direction of the quadrupole mass filter 11 and specified by the action of the electric field formed by the high-frequency voltage and the DC voltage applied to the quadrupole mass filter 11. Only ions having a mass-to-charge ratio (precursor ions) pass through the quadrupole mass filter 11 and are introduced into the collision cell 12.

  The collision cell 12 is filled with CID gas, and the precursor ions come into contact with the CID gas and are split by collision-induced dissociation to generate various product ions. Product ions exiting the collision cell 12 are introduced into the space in the long axis direction of the quadrupole mass filter 16, and are generated by the action of an electric field formed by the high-frequency voltage and the DC voltage applied to the quadrupole mass filter 16. Only product ions having a specific mass-to-charge ratio pass through the quadrupole mass filter 16 and reach the detector 17. For example, the mass-to-charge ratio of ions passing through the first-stage quadrupole mass filter 11 is fixed, and the mass-to-charge ratio of ions passing through the third-stage quadrupole mass filter 16 is scanned within a predetermined range, thereby detecting the detector. The data processing unit 20 that has received the detection signal from 17 can create a mass spectrum of product ions for a specific precursor ion.

  In the mass spectrometer of the present embodiment, a characteristic system check operation is executed at the request of an analyst (user) before executing the MS / MS analysis as described above. FIG. 2 is a flowchart showing the control operation of this system check.

  Prior to the execution of the MS / MS analysis, the analyst instructs the execution of the system check by performing a predetermined operation at the input unit 36 (step S1), and the gas pressure determination unit 34 of the control unit 33 receives the instruction. The gas pressure P1 detected by the first vacuum gauge 31 in the first intermediate vacuum chamber 4 is read (step S2), and it is determined whether or not the gas pressure P1 is equal to or lower than a preset low vacuum side threshold Pa. (Step S3). The low vacuum side threshold Pa and the high vacuum side threshold Pb described later may be either a value preset by the apparatus manufacturer or a value preset by the user from the input unit 36. If P1 ≦ Pa in step S3, it is determined that the gas pressure in the first intermediate vacuum chamber 4 is too low, and the low vacuum state is recorded as [Fail] (step S4). On the other hand, if P1> Pa, the low vacuum state is recorded as [Pass] (step S5).

  Next, the gas pressure determination unit 34 reads the gas pressure P2 detected by the second vacuum gauge 32 in the analysis chamber 10 (step S6), and the gas pressure P2 is less than or equal to a preset high vacuum side threshold value Pb. It is determined whether or not there is (step S7). If P2 ≦ Pb, it is determined that the gas pressure in the analysis chamber 10 is too low, and the high vacuum state is recorded as [Fail] (step S8). On the other hand, if P2> Pb, the high vacuum state is recorded as [Pass] (step S9).

  Finally, the gas pressure determination unit 34 displays the low vacuum part state check results obtained in steps S4 and S5 and the high vacuum part state check results obtained in steps S8 and S9 on the screen of the display unit 35. (Step S10). That is, whether the low vacuum side gas pressure in the first intermediate vacuum chamber 4 is [Fail] or [Pass], or the high vacuum side gas pressure in the analysis chamber 10 is [Fail] or [Pass]. ] Is displayed on the screen of the display unit 35. Further, if necessary, the check result may be printed out as a report. The analyst looks at the display result and confirms the latest state of the system.

  For example, if the supply of CID gas to the collision cell 12 through the gas supply pipe 14 stagnate, the amount of gas flowing out from the collision cell 12 to the outside (inside the analysis chamber 10) decreases, so the inside of the analysis chamber 10 The degree of vacuum tends to be too high. On the other hand, if the supply amount of the CID gas into the collision cell 12 decreases, it becomes difficult for ions to dissociate in the collision cell 12, and the production amount of product ions decreases and the detection sensitivity of product ions decreases. Therefore, when a check result indicating that the high vacuum side gas pressure state is [Fail] is obtained, the analyst checks a part related to the supply of CID gas in the apparatus. Specifically, the CID gas supply pressure, the presence / absence of gas leakage in the middle of the gas supply pipe 14, the operation of the gas supply valve 15 and the like should be checked.

  On the other hand, when the heating capillary 3 is clogged and the inflow of gas from the ionization chamber 1 to the first intermediate vacuum chamber 4 is reduced, the degree of vacuum in the first intermediate vacuum chamber 4 tends to be too high. When the heating capillary 3 is clogged, the amount of ions flowing together with the gas itself is reduced, and as a result, the detection sensitivity of the detector 17 is lowered. Therefore, if a check result indicating that the low vacuum side gas pressure state is [Fail], the analyst may check whether the heating capillary 3 is clogged.

  As described above, in the mass spectrometer of the present embodiment, the system check is executed prior to the execution of the analysis, thereby allowing the analyst to malfunction the device relating to the CID gas supply, lack of maintenance, or clogging of the heating capillary 3. You can know in advance. Thereby, it is possible to avoid performing useless analysis in a situation where sufficient signal strength cannot be obtained.

In the above embodiment, although the gas pressure in the system check was determined only too low, as mentioned in the opening paragraph of the present specification, suitable analysis if guitar to a high gas pressure Therefore, it is determined whether the gas pressure is within the range between the predetermined upper limit value and the lower limit value, and different warnings are displayed when the lower limit value is exceeded and when the upper limit value is exceeded. You may do it.

  Further, in the above embodiment, the supply failure of the CID gas supplied to the collision cell is determined in the high vacuum side gas pressure state. However, the present invention is not limited to the cell (chamber) disposed in the vacuum chamber which is a high vacuum atmosphere. ) And mass spectrometers having components that perform operations on ions by introducing a gas from the outside into a specific region. Specifically, the present invention is also applied to a case where a linear ion trap or a three-dimensional quadrupole ion trap is used and a cooling gas is supplied to the inside of the ion trap to cool the ions temporarily. It is clear that it can be applied. In addition, it is obvious that other modifications, additions, and modifications are appropriately included in the scope of the claims of the present application within the scope of the present invention.

DESCRIPTION OF SYMBOLS 1 ... Ionization chamber 2 ... Electrospray nozzle 3 ... Heating capillary 4 ... 1st intermediate vacuum chamber 5 ... 1st ion guide 6 ... Skimmer 7 ... 2nd intermediate vacuum chamber 8 ... 2nd ion guide 9 ... Ion passage hole 10 ... Analysis Chamber 11 ... First stage quadrupole mass filter 12 ... Collision cell 13 ... Second stage quadrupole 14 ... Gas supply pipe 15 ... Gas supply valve 16 ... Third stage quadrupole mass filter 17 ... Detector 20 ... Data Processing unit 21 ... Rotary pumps 22, 23 ... Turbo molecular pumps 31, 32 ... Vacuum gauge 33 ... Control unit 34 ... Gas pressure determination unit 35 ... Display unit 36 ... Input unit

Claims (2)

A vacuum chamber to be evacuated, an operation region that communicates with the vacuum chamber and holds a gas supplied from the outside in order to perform a predetermined operation on ions before mass analysis, and is disposed in the vacuum chamber, In a mass spectrometer comprising: a mass analyzer that separates ions after being operated in an operation region according to a mass-to-charge ratio; and a detector that detects the separated ions.
a) pressure detecting means for detecting a gas pressure inside the vacuum chamber;
b) an abnormality determining unit that determines that the gas supply to the operation region is abnormal when the gas pressure detected by the pressure detecting unit before execution of the analysis is equal to or lower than a predetermined threshold;
A mass spectrometer comprising:   2. The mass spectrometer according to claim 1, wherein the operation region is a collision cell disposed in the vacuum chamber in order to dissociate the ions by colliding the ions with a predetermined gas, and the mass analyzer. Is a mass analyzer in the subsequent stage that separates the product ions generated in the collision cell according to the mass-to-charge ratio, and the precursor ion having a specific mass-to-charge ratio is selected from various ions in the preceding stage of the collision cell. And a mass spectrometer in the previous stage for feeding into the collision cell.

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