JP5094362B2 - Mass spectrometer and control method thereof - Google Patents

Description

  The present invention relates to a mass spectrometer and a control method thereof, and more particularly to a technique suitable for a mass spectrometer having an ion trap.

  In a mass spectrometer having an ion trap, for example, as disclosed in Patent Document 1, it is possible to perform MS / MS measurement in an ion trap section. After the sample is ionized by the ionization unit, the sample is introduced into the ion trap unit to accumulate ions. Next, the parent ion is isolated by using a filtered noise field (FNF). Next, collision-induced dissociation (CID) is caused, and the dissociated ions are detected by the ion detector.

  On the other hand, in the field of protein analysis, electron capture dissociation (ECD) is attracting attention as another dissociation means. This is because CID is suitable as a research / analysis means for post-translational modification because it has a feature such that the side chain of an amino acid sequence is easily cut, whereas the main chain of an amino acid sequence is easily cut in ECD.

  In recent years, mass spectrometers in which an ECD is connected as an ion trap part and an ion dissociation part have been developed. In such an apparatus, since the data measured by the CID and the data measured by the ECD can be collected by one apparatus, the accuracy of protein analysis can be expected to be improved.

U.S. Pat. No. 4,736,101

  In the mass spectrometer having an ion trap part and an ion dissociation part such as ECD, control of the ion trap when performing MS / MS measurement will be described.

  FIG. 3 shows the control of the ion trap unit and the timing of the ion dissociation unit and the ion detection unit in the comparison method. When ions are introduced into the ion trap part, the ion accumulation stage is first controlled. In the ion accumulation stage, the high-frequency voltage and the auxiliary AC signal are controlled. FNF is output as an auxiliary AC signal, and ions having a mass-to-charge ratio near the parent ion are roughly excluded. Next, control is passed to the parent ion isolation step. In this stage, similarly to the ion accumulation stage, the high-frequency voltage and the auxiliary AC signal are controlled, and FNF is output as the auxiliary AC signal.

  In the comparative example of FIG. 3, the parent ion isolation step is further divided into two steps. In the first stage, a wide range of ions is left around the mass-to-charge ratio of the parent ions, and other ions are excluded. At a later stage, a narrower range of ions is left around the mass-to-charge ratio of the parent ion, and other ions are excluded. Next, control proceeds to the parent ion discharge stage. In the parent ion discharge stage, the high-frequency voltage is controlled to discharge the ions in the ion trap all at once and introduce them into the ion dissociation part. In the ion dissociation part, after the introduced ions are dissociated, the dissociated ions are discharged. Ions discharged from the ion dissociation unit are introduced into the ion detection unit, and ion detection is performed. In the ion trap, the ion accumulation stage is started again at this timing. Thereafter, these controls are repeated.

  This comparison method has a problem that the throughput is not improved as compared with the method of performing ion dissociation in the ion trap part, and the throughput may be lowered depending on the time taken for ion dissociation in the ion dissociation part.

  One object of the present invention is to improve the throughput of MS / MS measurement in a mass spectrometer having an ion trap part and an ion dissociation part.

  One feature of the present invention is that, in a mass spectrometer having an ion trap part and an ion dissociation part, when ion dissociation is executed by the ion dissociation part, it is sufficient that only the parent ions can be discharged from the ion trap part. It is not necessary to isolate the parent ion. Therefore, the throughput of MS / MS measurement is improved by performing control of discharging only the parent ions by the resonance emission method in the ion trap section.

  According to one characteristic of the present invention, in a mass spectrometer having an ion trap part and an ion dissociation part, the throughput of MS / MS measurement can be improved.

  Examples of the present invention will be described below. In an embodiment of the present invention, for example, in a mass spectrometer having an ion trap part and an ion dissociation part, when ion dissociation is executed by the ion dissociation part, it is sufficient that only parent ions can be discharged from the ion trap part. Note that it is not necessary to isolate the parent ion in the trap. Therefore, the throughput of MS / MS measurement is improved by performing control of discharging only the parent ions by the resonance emission method in the ion trap section.

  Here, the resonance emission method will be described for the ion trap. In the ion trap, ions that vibrate stably have a unique fundamental frequency for each mass-to-charge ratio. By applying a minute AC voltage having the same frequency as the fundamental frequency of the parent ion to the ion trap, only the parent ion can be discharged from the ion trap. Furthermore, the resonance emission method is a technology that discharges ions with a specific mass-to-charge ratio from the ion trap part. Normally, the mass-to-charge ratio of ions discharged from the ion trap part is continuously changed by continuously changing the high-frequency voltage. It is used to obtain a spectrum by detecting it by changing it automatically. Or it is used to measure only ions with a specific mass-to-charge ratio and see the change. In an embodiment of the present invention, for example, this resonance emission technique is combined with an ion dissociation part outside the ion trap part to improve the throughput of MS / MS measurement.

  FIG. 4 is a diagram showing an example of a mass spectrometer in the embodiment of the present invention. An ion trap unit 42 that accumulates, isolates, dissociates, and discharges ions generated by the ion generation unit 41, and a DEF lens 46 that introduces ions discharged from the ion trap unit to the ion dissociation unit 43 and ions that dissociate ions. The dissociation unit 43, the ion detection unit 44 that detects the ions discharged from the ion dissociation unit 43, the ion trap unit 42, the DEF lens, and the control unit 45 that controls the operations of the ion dissociation unit 43 and the ion detection unit 44. Have In this apparatus, the ion trap unit 42 includes a linear trap, the ion dissociation unit 43 includes an ECD, and the ion detection unit 44 includes a TOF.

  In the case of performing MS / MS measurement, ions discharged from the ion trap unit 42 are controlled by the control unit 45 and the DEF lens 46 to introduce ions into the ion dissociation unit 43. When MS / MS measurement is not performed, the control unit 45 controls the DEF lens 46 to introduce ions into the ion detection unit 44.

  In the ion dissociation part 43, an ECD reaction is caused to the introduced ions to dissociate the ions. The dissociated ions pass through the DEF lens 46 controlled by the control unit 45 and are introduced into the ion detection unit 44 to be detected.

  FIG. 1 shows the control of the ion trap unit and the timing of the ion dissociation unit and ion detection unit in the embodiment of the present invention.

  Furthermore, FIG. 5 shows an example of a control flowchart of the mass spectrometer in the embodiment of the present invention. The contents shown in FIG. 5 are as follows. The ion trap unit calculates a high-frequency voltage and auxiliary AC signal for storing parent ions and a high-frequency voltage and auxiliary AC signal for discharging parent ions before introducing ions. Next, ions are introduced, and the parent ions are accumulated by starting the output of the high frequency voltage and the auxiliary AC signal for accumulating the parent ions. After a certain time, the output of the high-frequency voltage and auxiliary AC signal for storing parent ions is stopped, and the output of the high-frequency voltage and auxiliary AC signal for discharging parent ions is started. At the same time, the ion dissociation control of the ion dissociation part is started. In the ion trap unit, the high-frequency voltage for discharging the parent ions and the auxiliary AC signal are output for a certain period of time, then the high-frequency voltage is controlled to 0 V, the output of the auxiliary AC signal is stopped, and a certain period of time is waited. The sum of the output time of the high-frequency voltage and auxiliary AC signal for discharging the parent ions and the waiting time after the output is stopped is the same as the ion dissociation control time.

  In the ion dissociation part, ion dissociation is controlled, and then ion discharge is controlled. At the same time, the ion detector is controlled to detect ions.

  Usually, since the control for one parent ion is repeated a plurality of times to perform one measurement, the processing after the parent ion accumulation high-frequency voltage / auxiliary AC signal output is repeated a plurality of times.

  The control of the ion trap part in the ion accumulation stage is the same as the comparison method shown in FIG.

  After the ion accumulation stage, the process proceeds to the parent ion discharge stage. In the parent ion discharge stage, the high-frequency voltage and the auxiliary AC signal are controlled. The auxiliary AC signal is a single frequency signal having a fundamental frequency corresponding to the mass-to-charge ratio of the parent ion. When the auxiliary AC signal is applied, only the parent ions are discharged.

  At the same time as the discharge of parent ions from the ion trap portion, the ion dissociation portion introduces parent ions discharged from the ion trap, dissociates, and then discharges the dissociated ions. Ions discharged from the ion dissociation unit are introduced into the ion detection unit, and ion detection is performed. In the ion trap, the ion accumulation stage is started again at this timing. Thereafter, these controls are repeated.

  As described above, in this method, the time required for the parent ion isolation step in the comparative method can be saved. In terms of a quantitative effect, in a general usage where the time of the ion accumulation step is 20 ms to 100 ms, the parent ion isolation step is usually 10 to 30% of the total mass analysis step. The throughput of MS / MS measurement can be improved by 5 to 20%.

  FIG. 2 shows the control of the ion trap unit and the timing of the ion dissociation unit and the ion detection unit when there are a plurality of parent ions in Example 2 of the present invention. Here, a case where there are two parent ions will be described.

  The control of the ion trap part in the ion accumulation stage is almost the same as the comparison method shown in FIG. However, FNF that leaves a plurality of parent ions is output here.

  After the ion accumulation stage, the process proceeds to the parent ion 1 discharge stage. In the parent ion 1 discharge stage, the high frequency voltage and the auxiliary AC signal are controlled. The auxiliary AC signal is a single frequency signal having a fundamental frequency corresponding to the mass-to-charge ratio of the parent ion 1. When the auxiliary AC signal is applied, only the parent ion 1 is discharged.

  At the same time as the discharge of parent ions from the ion trap portion, the ion dissociation portion introduces parent ions discharged from the ion trap, dissociates, and then discharges the dissociated ions.

  When the parent ion 1 discharging step is completed, the ion trap unit moves to the parent ion 2 discharging step. At the same time, the ion detecting unit detects ions discharged from the ion dissociating unit.

  In the ion trap part and the ion dissociation part, the same control as the parent ion 1 is performed on the parent ion 2.

  When the parent ion 2 discharge step is completed, ions discharged from the ion dissociation unit are introduced into the ion detection unit, and ion detection is performed. In the ion trap, the ion accumulation stage is started again at this timing. Thereafter, these controls are repeated.

  As described above, in the method of this embodiment, when there are a plurality of parent ions, the ion accumulation time × (number of parent ions−1) can be further omitted from the first embodiment.

  In the present embodiment, as an apparatus configuration, connection with an ion trap part-ion dissociation part-ion detection part is described. Then, as a method for separating parent ions in MS / MS measurement, a comparative method (a broadband auxiliary AC voltage (combined wave having a plurality of frequencies) is applied in the ion trap portion), so that ions other than the parent ions are discharged from the ion trap portion. ), Instead of applying the auxiliary AC voltage of the fundamental frequency (single frequency) of the parent ion (resonance emission method), it is explained that the parent ion is discharged from the ion trap part and led to the ion dissociation part. . As the number of parent ions (mass number) that can be isolated by one ion accumulation, in the present embodiment, a plurality of parent ions are simply used in comparison with the comparison method (only one kind of parent ions of mass number). It is explained that MS / MS measurement is possible apart.

  This explains that an improvement in throughput of MS / MS measurement can be achieved.

  A part of matters disclosed in this specification are listed as follows.

  1. An ion generator, an ion trap that accumulates, isolates, dissociates, and discharges ions generated by the ion generator, an ion dissociator that dissociates ions discharged from the ion trap, and the ion dissociator A method for controlling a mass spectrometer having an ion detector that detects ions ejected from a gas, and a controller that controls at least the operation of the ion trap unit, the resonance method for ejecting specific ions from the ion trap unit A method for controlling a mass spectrometer, characterized by performing emission and dissociating the specific ions at the ion dissociation part.

  2. In 1 above, in one ion accumulation in the ion trap unit, a plurality of parent ions as the specific ions are sequentially emitted in resonance from the smallest mass, and the plurality of parent ions are sequentially ionized and ion detected. A method for controlling a mass spectrometer.

  3. In the above 1, the specific ion includes at least a first specific ion and a second specific ion, and the ion detection unit detects the ion with respect to the first specific ion and the ion trap with respect to the second specific ion. A method for controlling a mass spectrometer, characterized in that accumulation of ions in the unit is performed at least partially overlapping with the second step.

  4). In 1 above, the specific ion includes at least a first specific ion and a second specific ion, and the ion detection unit detects the ion with respect to the first specific ion and the ion dissociation with respect to the second specific ion. A method of controlling a mass spectrometer, wherein ion dissociation at a portion is performed at least partially overlapping.

5. An ion trap unit for accumulating, isolating, dissociating and discharging ions generated by the ion generation unit, an ion dissociation unit for dissociating ions discharged from the ion trap unit, and an ion discharged from the ion dissociation unit An ion detection unit to detect, and a control unit that controls at least the operation of the ion trap unit,
The said control part performs resonance emission in order to discharge | emit specific ion from an ion trap part, and controls to dissociate specific ion in the said ion dissociation part, The mass spectrometer characterized by the above-mentioned.

  6). 5. In the above 5, the specific ion includes at least a first specific ion and a second specific ion, and the control unit detects the ion in the ion detection unit related to the first specific ion, and the second specific ion. The mass spectrometer is controlled so that the accumulation of ions in the ion trap section relating to ions is performed at least partially overlapping with the second step.

  7). In the fifth aspect, the specific ions include at least a first specific ion and a second specific ion, and the control unit includes the first specific ion and at least a first specific ion. The mass spectrometer according to claim 5, wherein the fifth step relating to specific ions of the second and the second step relating to the second specific ions overlap at least partially.

  8). In 5 above, the control unit includes the ion detection in the ion detection unit related to the first specific ion, the second specific ion, and the specific ion includes at least a first specific ion and a second specific ion. A mass spectrometer characterized by performing control so that ion dissociation at the ion dissociation part relating to ions is performed at least partially overlapping.

  9. A first step of ionizing a sample; a second step of accumulating the ionized sample; a third step of discharging specific ions out of the ionized sample by resonant emission; and the specific ions A mass spectrometric method comprising a fourth step of ion dissociation and a fifth step of detecting the ion-dissociated specific ions.

  10. 9. The mass spectrometric method according to 9, wherein, in the third step, a plurality of parent ions as specific ions are sequentially subjected to resonance emission from the smallest mass.

  11. In 9 above, the specific ion includes at least a first specific ion and a second specific ion, the fifth step relating to the first specific ion, and the second step relating to the second specific ion, Is a mass spectrometric method characterized in that at least partly overlaps.

  12 In 9 above, the specific ion includes at least a first specific ion and a second specific ion, the fifth step relating to the first specific ion, and the fourth step relating to the second specific ion, Is a mass spectrometric method characterized in that at least partly overlaps.

The figure which shows an example of the timing of the control of an ion trap part in the Example of this invention, an ion dissociation part, and an ion detection part. The figure which shows an example of the timing of control of an ion trap part and ion dissociation part, and an ion detection part in case the multiple parent ion in the Example of this invention exists. The figure which shows an example of control of the ion trap part of a comparison system, and the timing of an ion dissociation part, and an ion detection part. The figure which shows an example of the mass spectrometer in the Example of this invention. The figure which shows an example of the control flowchart of the mass spectrometer in the Example of this invention.

Explanation of symbols

41 Ion generation unit 42 Ion trap unit 43 Ion dissociation unit 44 Ion detection unit 45 Control unit

Claims (1)

An ion trap unit for accumulating, isolating, dissociating and discharging ions generated by the ion generation unit, an ion dissociation unit for dissociating ions discharged from the ion trap unit, and an ion discharged from the ion dissociation unit An ion detection unit to detect, a DEF lens for switching whether ions discharged from the ion trap unit are introduced into the ion detector or the ion dissociation unit, and at least the ion trap unit and the ion dissociation unit A control unit that controls the operation of the DEF lens and the ion detection unit,
The ion trap part and the ion dissociation part have cap electrodes on both sides,
The DEF lens linearly moves ions introduced into the ion detector, bends the traveling direction of ions introduced into the ion dissociation portion by 90 degrees, and further changes the traveling direction of ions dissociated at the ion dissociation portion by 90 degrees. Bent and introduced into the ion detector,
The control unit performs resonance emission to discharge specific ions from the ion trap unit, and controls to dissociate specific ions in the ion dissociation unit,
The specific ions include at least a first specific ion and a second specific ion,
The control unit controls the discharge of the first specific ions in the ion trap unit and the dissociation of the first specific ions in the ion dissociation unit at the same time,
The control unit simultaneously discharges the second specific ions in the ion trap unit, dissociates the second specific ions in the ion dissociation unit, and detects the first specific ions in the ion detection unit. A mass spectrometer characterized by being controlled to be performed.

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