JP6075311B2 - Ion trap mass spectrometer and mass spectrometry method using the apparatus - Google Patents

Description

  The present invention relates to an ion trap mass spectrometer and a mass spectrometry method using the apparatus, and more particularly, to an ion source that generates ions in a pulsed manner, such as an ion source using a matrix-assisted laser desorption ionization (MALDI) method. The present invention relates to an ion trap mass spectrometer that captures ions in an ion trap and then performs mass spectrometry, and a mass spectrometry method using the apparatus.

In a mass spectrometer equipped with an ion trap capable of capturing ions derived from sample components, an ion trap having a specific mass-to-charge ratio and a dissociation operation for ions having a specific mass-to-charge ratio are performed in the ion trap. MS ⁿ analysis can be performed. This type of mass spectrometer includes a configuration in which ions separated from the ion trap are sequentially detected by a detector arranged outside using the mass separation function of the ion trap itself, and ions simultaneously discharged from the ion trap are externally detected. And a configuration in which ions are separated into mass-to-charge ratios by introducing them into a mass analyzer (typically a time-of-flight mass analyzer) arranged in a cell, and the separated ions are detected by a detector. Yes. In this specification, these are referred to as an ion trap mass spectrometer.

  The performance of the ion trap mass spectrometer is greatly influenced by the density of ions trapped in the ion trap, that is, the space charge density. That is, when the density of ions increases in the ion trap and the space charge density exceeds a certain threshold value, mass resolution and mass accuracy are lowered. This is because the space charge density due to the ions trapped in the ion trap affects the spatial distribution of ions in the ion trap and the trajectory when ions are drawn out of the ion trap. For this reason, in order to improve the mass resolution and mass accuracy of the ion trap mass spectrometer, it is preferable to suppress the amount of ions trapped in the ion trap to an appropriate amount so as not to become excessive.

In an ion trap mass spectrometer using an ion source that continuously generates ions, such as an electrospray ion (ESI) source, as an ion source, ions are generated at a gate electrode or the like disposed in an ion path upstream of the ion trap. A configuration is adopted in which the amount of ions introduced into the ion trap is adjusted by adjusting the passage time width.
In contrast, in an ion trap mass spectrometer using an ion source that generates ions in packets, such as a MALDI ion source, ions to the ion trap are less than the amount of ions in one packet generated at a time by the ion source. The amount of introduction cannot be adjusted.

  Patent Document 1 discloses a technique for reducing the adverse effect of space charge in an ion trap on mass spectrometry in such an ion trap mass spectrometer. That is, in the method disclosed in the document, the mass-to-charge ratio range to be measured is divided into a plurality of divided relatively narrow mass-to-charge ratio ranges (hereinafter, this mass-to-charge ratio range is divided into divided mass-to-charge ratio ranges). Mass spectrometry is performed on the same sample every time.

  Specifically, after all the ions generated from the sample are once trapped in the ion trap, a predetermined FNF (Filtered Noise Field) signal is applied to the ion trap, so that one target divided mass-to-charge ratio range is obtained. Other ions are resonantly excited and discharged from the ion trap. Thus, after leaving only ions included in one divided mass-to-charge ratio range in the ion trap, mass analysis is performed on the ions. The same measurement is performed for each of a plurality of divided mass-to-charge ratio ranges, a mass spectrum for each divided mass-to-charge ratio range is acquired, and finally, the plurality of mass spectra are connected to each other to cover a wide mass-to-charge ratio range. Create a mass spectrum. In addition, when determining the division of the divided mass-to-charge ratio range, there are a mass-to-charge ratio range including an ion peak with a high signal intensity and a mass-to-charge ratio range including an ion peak with a weak signal intensity. It is also shown in Patent Document 1 that the influence of space charge on the measurement of an ion peak having a weak signal intensity can be reduced by entering a different divided mass-to-charge ratio range.

  FIG. 6 (a) is a mass spectrum measured for a sample that is a peptide mixture by a normal measurement method, that is, without eliminating ions in the ion trap. On the other hand, FIG. 6 (b) shows that ions other than the single peptide ion (ACTH7-38) (actually other than the mass-to-charge ratio range indicated by the dotted line in the figure) by applying a predetermined FNF signal to the ion trap. It is a mass spectrum measured by removing (ion) from the ion trap.

  In a normal measurement method, since all ions trapped in the ion trap are reflected in the mass spectrum, ion peaks having various signal intensities appear in the mass spectrum shown in FIG. On the other hand, in the mass spectrum shown in FIG. 6B, no peak corresponding to the excluded ion appears, and instead, the peak intensity of the single peptide ion is equal to the peak intensity in the usual measurement method. Compared to about 4 times. That is, it can be confirmed that the detection sensitivity of the target ions is improved by removing unnecessary ions other than the target ions from the ion trap prior to the mass analysis. This is because in the normal measurement method, the trajectory of ions expands due to the effect of space charge in the ion trap, and when ions are extracted from the ion trap, some ions collide around the ion outlet and the amount of ions On the other hand, if unnecessary ions are eliminated, the influence of space charge is reduced, and the decrease in the amount of ions when ions are extracted can be considered to be small.

US Pat. No. 5,479,012

  However, in the measurement method described in Patent Document 1, it is necessary to perform the measurement for the divided mass-to-charge ratio range at least once for the same sample. For this reason, the number of times of measurement execution is increased and the measurement time is remarkably increased as compared with a normal measurement method. Further, in the ion trap mass spectrometer using the MALDI ion source, the sample is scraped every time the laser beam is irradiated in the ion source. Therefore, if the number of times of measurement increases, not only the sample is wasted, but all There is also a risk that the sample will be depleted before the measurement is completed.

  Further, as another method for reducing the influence of space charge, it is conceivable to reduce the amount of ions generated by reducing the intensity of laser light applied to the sample in the MALDI ion source. As a result, the space charge density in the ion trap is lowered, and characteristics such as ion peak resolution are improved. However, in this case, since the amount of ions trapped in the ion trap is reduced as a whole, even if the loss of ions when the ions are extracted is small, there is a possibility that the detection sensitivity of the ions to be measured is lowered. In general, since the relationship between the intensity of the irradiated laser beam and the amount of ion generation varies greatly, it is difficult to accurately adjust the amount of ion generation even if the laser beam intensity is adjusted.

  The present invention has been made in order to solve the above-mentioned problems, and the object of the present invention is to provide a space in the ion trap without causing problems such as an increase in measurement time, wasted sample, and a decrease in detection sensitivity. An ion trap mass spectrometer capable of ensuring high mass accuracy and mass resolution by reducing the influence of electric charges, and a mass spectrometry method using the apparatus.

An ion trap mass spectrometer according to the present invention, which has been made to solve the above problems, includes an ion source that generates ions in a packet form from a sample and a plurality of electrodes, and traps ions in a space surrounded by the electrodes. An ion trap, and the ions to be measured trapped in the ion trap are separated and detected for each mass-to-charge ratio by the ion trap itself, or the ions to be measured are discharged from the ion trap and the ions In an ion trap mass spectrometer that separates and detects each mass to charge ratio by a mass analyzer provided outside the trap,
a) An ion peak having a relatively large influence on the space charge in the ion trap based on the result of performing mass analysis on the target sample over a predetermined mass-to-charge ratio range that is continuous or discontinuous by the apparatus. A peak identification part to be identified;
b) After trapping ions from the target sample in the ion trap, an operation of excluding ions in the mass-to-charge ratio range corresponding to the peak specified by the peak specifying unit from the ion trap is performed in the ion trap. A control unit for controlling the voltage applied to each of the plurality of electrodes constituting the ion trap so as to perform mass spectrometry on the remaining ions;
c) A processing unit that creates a final mass analysis result using results obtained by performing a plurality of mass analyzes on the target sample performed under the control of the control unit using the result of the peak specifying unit. When,
It is characterized by having.

In addition, the mass spectrometry method according to the present invention made to solve the above problems includes an ion source that generates ions in a packet form from a sample and a plurality of electrodes, and captures ions in a space surrounded by the electrodes. An ion trap, and the ions to be measured trapped in the ion trap are separated and detected by the mass trap ratio by the ion trap itself, or the ions to be measured are discharged from the ion trap and the ion trap A mass spectrometric method using an ion trap mass spectrometer that separates and detects each mass to charge ratio by a mass analyzer provided outside
Based on the result of performing mass analysis over a predetermined mass-to-charge ratio range that is continuous or non-continuous by the apparatus on the target sample, an ion peak that has a relatively large effect on the space charge in the ion trap is identified. Peak identification step;
After trapping ions from the target sample in the ion trap, an operation of removing ions in the mass-to-charge ratio range corresponding to the peak identified in the peak identifying step from the ion trap was performed and remained in the ion trap. A mass spectrometry step for performing mass spectrometry on the ions,
A final mass analysis result is created using a result obtained by executing mass analysis by the mass analysis step using the result of the peak specifying step a plurality of times for the target sample.

  In the present invention, the ion trap may be either a three-dimensional quadrupole ion trap or a linear ion trap. However, in general, since the linear ion trap has a larger amount of ions that can be trapped than the three-dimensional quadrupole ion trap, space charge is less likely to be a problem. Therefore, the present invention is particularly effective for an ion trap mass spectrometer using a three-dimensional quadrupole ion trap.

  In the present invention, the ion source is a MALDI ion source, a laser desorption ionization method (LDI) without using a matrix, a surface assisted laser desorption ionization method (SALDI), a secondary ion mass spectrometry method (SIMS), a desorption method. Electrospray ionization method (DESI), electrospray support / laser desorption ionization method (ELDI), and the like.

  In the ion trap mass spectrometer according to the present invention, when a result of performing mass analysis over a predetermined mass-to-charge ratio range that is continuous or discontinuous with respect to the target sample is obtained, the peak specifying unit Based on this, an ion peak having a relatively large influence on the space charge in the ion trap is identified. Here, the predetermined mass-to-charge ratio range that is discontinuous means that a part of the mass-to-charge ratio range in a certain continuous mass-to-charge ratio range has already been removed. That is, under the control of the control unit, when an operation of removing ions in the mass-to-charge ratio range corresponding to one or more peaks specified by the peak specifying unit from the ion trap is performed, a predetermined mass charge The ratio range can be discontinuous.

  Specifically, the peak specifying unit calculates, for example, the SN ratio of an ion peak appearing in a spectrum obtained by integrating data collected by mass spectrometry, and the space charge in the ion trap is calculated based on the SN ratio. It can be set as the structure which identifies the ion peak with a comparatively large influence with respect to. If this S / N ratio is large, it is estimated that the signal intensity of the ion peak is large. Such ions have a relatively large amount of ions themselves and cause space charge in the ion trap. On the other hand, such ion-derived peaks can be sufficiently detected even if the number of data integration is small. Therefore, the peak specifying unit may compare the SN ratio with a predetermined threshold value and specify the ion peak when the threshold value is exceeded.

  When a certain peak is specified by the peak specifying unit, the control unit captures ions in the mass-to-charge ratio range corresponding to the specified peak after capturing ions from the target sample in the ion trap. A voltage is applied to each of the plurality of electrodes constituting the ion trap so that the ion trap is subjected to an operation such as resonance excitation to perform mass analysis on the ions remaining in the ion trap. As a result, prior to mass analysis, ions with a relatively large amount of ions are excluded from the ion trap, so the effect of space charge is reduced when attempting to perform mass analysis, and ions are not excluded. Compared with, mass resolution and mass accuracy are improved.

  If the peak identification unit repeats the peak identification based on the mass analysis result and the mass analysis under the control of the control unit reflecting the result, the amount of ions in the various ions generated from the sample Are removed from the mass-to-charge ratio range of the mass analysis target in order from ions having a relatively large number. In other words, the number of integrations increases for ion peaks where the amount of generated ions is small and the signal intensity is weak, and the data obtained in a state where the effect of space charge due to large amounts of ions is reduced is reflected in the final result. Will be. On the other hand, the peak of ions that are generated in a large amount and have a high signal intensity has a small number of integrations, so that it is difficult to perform data integration that is substantially unnecessary. Therefore, the measurement time is not unnecessarily lengthened, and the influence of space charge can be reduced to detect even a very small amount of component.

  According to the ion trap mass spectrometer and the mass spectrometry method of the present invention, only a substantially necessary minimum number of mass analyzes are performed for relatively large quantities of ions that can cause space charge in the ion trap. On the other hand, for the small amount of ions, the result of mass spectrometry performed under conditions where the influence of space charge is small is reflected in the final result. Thereby, high mass resolution and mass accuracy can be realized for both a large amount component and a small amount component without incurring unnecessary length of measurement time. Moreover, a trace component can be detected with high sensitivity.

The block diagram of the principal part of the ion trap time-of-flight mass spectrometer by one Example of this invention. Explanatory drawing of the characteristic measurement operation | movement in the ion trap time-of-flight mass spectrometer of a present Example. The flowchart of the control at the time of performing the characteristic measurement in the ion trap time-of-flight mass spectrometer of a present Example, and a process. The figure which shows an example of the comparison of the peak intensity of the measuring method by this invention, and the conventional method. The figure which shows the peak intensity improvement effect of the measuring method by this invention. A mass spectrum (a) measured by a conventional measurement method and a mass spectrum (b) measured by performing an operation of removing ions other than predetermined ions from the ion trap.

Hereinafter, an ion trap time-of-flight mass spectrometer as an embodiment of the present invention will be described in detail with reference to the accompanying drawings.
An ionization unit 1, an ion trap 2, a time-of-flight mass analyzer 3, and an ion detector 4 are arranged inside a vacuum chamber (not shown), and a detection signal from the ion detector 4 is sent to the data processing unit 5. Entered.
Here, the ionization unit 1 is a MALDI ion source, and an ion extraction electric field between the laser irradiation unit 13 driven by the laser driving unit 6, the sample plate 11 on which the sample 12 is formed, and the sample plate 11. And an extraction electrode 14 that forms

  The ion trap 2 is a three-dimensional quadrupole ion trap including one annular ring electrode 21 and a pair of end cap electrodes 22 and 24 provided so as to sandwich the electrode 21. An ion incident port 23 is formed substantially at the center of the inlet side end cap electrode 22, and an ion emission port 25 is formed substantially at the center of the outlet side end cap electrode 24 so as to be in a straight line with the ion incident port 23. . A high frequency voltage, a direct current voltage, or both are applied to the ring electrode 21 and the end cap electrodes 22 and 24 from the ion trap power supply unit 7 at appropriate timing.

  The data processing unit 5 has functions such as a spectrum data collection unit 51, a spectrum data integration unit 52, a peak SN ratio calculation unit 53, a peak SN ratio determination unit 54, etc. in order to carry out characteristic measurements in the apparatus of this embodiment. Includes blocks. The control unit 8 includes a measurement condition setting unit 81 and controls operations of the laser driving unit 6, the ion trap power supply unit 7, the data processing unit 5 and the like according to a predetermined sequence. The control unit 8 is connected to an operation unit 9 operated by a user and a display unit 10 for outputting analysis results and the like.

The basic mass analysis operation of the ion trap time-of-flight mass spectrometer of the present embodiment is as follows.
In response to an instruction from the control unit 8, the laser driving unit 6 drives the laser irradiation unit 13 to irradiate the sample 12 with pulsed laser light. As a result, various components contained in the sample 12 are ionized, and the generated ions are extracted by the electric field formed between the sample plate 11 and the extraction electrode 14 and sent out toward the ion trap 2. The packet-like ions are introduced into the ion trap 2 through the ion incident port 23. The introduced ions are captured by a high frequency electric field formed in the ion trap 2 by a high frequency high voltage applied to the ring electrode 21 from the ion trap power supply unit 7.

  Thereafter, in the ion trap 2, a cooling operation for attenuating the kinetic energy of the ions by bringing the ions into contact with the cooling gas introduced into the ion trap 2 is performed. At a predetermined timing after the cooling operation, the ion trap power supply unit 7 applies a predetermined DC voltage to the end cap electrodes 22 and 24 to give kinetic energy to the trapped ions. As a result, ions are accelerated all at once, discharged from the ion trap 2 through the ion outlet 25, and introduced into the flight space of the time-of-flight mass analyzer 3. Since each ion has a flight speed according to the mass-to-charge ratio, a time difference is generated while flying in the flight space, and the ions reach the ion detector 4 in order from the ions with the smallest mass-to-charge ratio. Upon receiving the detection signal from the ion detector 4, the data processing unit 5 creates a time-of-flight spectrum indicating the relationship between the flight time and the ion intensity of each ion starting from the ion emission time from the ion trap 2. A mass spectrum is created by converting the time of flight into a mass-to-charge ratio using the obtained mass calibration information.

  Next, in the ion trap time-of-flight mass spectrometer of the present embodiment, an operation when performing characteristic measurement with reduced influence of space charge in the ion trap 2 will be described. FIG. 3 is a flowchart of control and processing during this measurement, and FIG. 2 is an explanatory diagram of this measurement operation.

  Before the measurement, the user (analyst) first sets the total number of times P and the SN ratio threshold value Q using the operation unit 9 and instructs the start of measurement (step S1). The S / N ratio threshold Q may be set to a S / N ratio considered to be the minimum necessary for peak detection. In response to the measurement start instruction, the control unit 8 sets the integrated count value N, which is a processing variable, to 1 (step S2). Then, the measurement is started by setting the total mass-to-charge ratio range ML to MH (see FIG. 2A), which is a predetermined measurement object, as measurement conditions (step S3).

  That is, the control unit 8 drives the laser irradiation unit 13 via the laser driving unit 6 to irradiate the sample 12 with pulsed laser light, thereby capturing ions generated from the sample 12 in the ion trap 2. In the first measurement, since the total mass-to-charge ratio range is set as the measurement condition, the trapped ions are ejected from the ion trap 2 without performing the ion exclusion operation described later, and the time-of-flight mass spectrometry is performed. Mass analysis is performed by the instrument 3 (step S4). In the data processing unit 5, the spectrum data collecting unit 51 collects mass spectrum data based on the detection signal from the ion detector 4 (step S5). The spectrum data integration unit 52 integrates the collected mass spectrum data for each mass to charge ratio (step S6). Of course, since there is no data already obtained in the first measurement, the data obtained in the first measurement becomes the integrated data as it is.

  Subsequently, the peak SN ratio calculation unit 53 performs peak detection on the mass spectrum after data integration as shown in FIG. 2B, for example, and extracts a peak (step S7). The method of peak detection is not particularly limited, and various conventionally known methods can be used. Then, the peak SN ratio calculation unit 53 calculates the SN ratio for each extracted peak (step S8). The SN ratio of the peak can be obtained from, for example, the signal intensity at the peak top and the signal intensity in the mass-to-charge ratio region where it is guaranteed that no peak exists on the mass spectrum.

In general, when a mass spectrum including a peak with a signal intensity Is is integrated k times, assuming that the noise component is white noise, the final peak-to-noise ratio is calculated by the following equation (1). That is, the SN ratio of the peak increases in proportion to the square root of the number of integrations k.
SN ratio = {√ (k) / σ _n } Is (1)
Here, σ _n is the standard deviation of noise. From equation (1), an ion peak having a large signal intensity Is causing space charge in the ion trap 2 can be detected with a sufficiently high S / N ratio even if the number of integrations k is small. It can be seen that an ion peak having a smaller intensity Is has difficulty in securing an SN ratio necessary for detection unless the number of integrations k is sufficiently increased.

  That is, when the SN ratio of a certain peak calculated in step S8 is large, the amount of ions corresponding to the peak should be relatively large. Therefore, the peak SN ratio determination unit 54 compares the SN ratio of each peak calculated in step S8 with the SN ratio threshold Q (step S9), and if there is a peak indicating the SN ratio that is equal to or greater than the SN ratio threshold Q. (Yes in step S10), information such as the mass-to-charge ratio of the peak is notified to the measurement condition setting unit 81. Upon receiving this notification, the measurement condition setting unit 81 changes the measurement conditions so as to exclude the mass-to-charge ratio range corresponding to the one or more peaks from the mass-to-charge ratio range of the measurement target set at that time. (Step S11).

  Then, the spectrum display processing unit 55 displays the mass spectrum based on the data accumulated by the spectrum data accumulation unit 52 at that time on the screen of the display unit 10 through the control unit 8 (step S12).

  On the other hand, if it is determined in step S10 that there is no peak indicating an SN ratio equal to or higher than the SN ratio threshold Q, the process proceeds to step S12 without performing the process of step S11 described above, and is obtained at that time. The mass spectrum is displayed on the screen of the display unit 10.

  Thereafter, the control unit 8 determines whether or not the accumulated count value N matches the total accumulated number P (step S13), and if not, increments the accumulated count value N (step S14) and step S4. Return to. Immediately after it is determined in step S10 that there is at least one peak showing an SN ratio equal to or higher than the SN ratio threshold Q, and in step S11 the measurement conditions are changed so that the mass-to-charge ratio range corresponding to the peak is excluded. When returning from step S14 to S4, for example, as shown in FIG. 2C, a part of the mass-to-charge ratio range (ML to MH) to be measured is excluded. In addition, mass analysis is performed with a discontinuous mass-to-charge ratio range as measurement conditions.

  When such a discontinuous mass-to-charge ratio range is set as a measurement condition, various ions generated from the sample 12 by laser light irradiation are once trapped in the ion trap 2. A predetermined FNF signal corresponding to the measurement condition is applied to the end cap electrodes 22 and 24 by the trap power supply unit 7. This FNF signal is a broadband signal having a notch at a frequency corresponding to a mass-to-charge ratio range that should not be excluded (that is, to be left in the ion trap 2). Thereby, ions included in the mass-to-charge ratio range to be excluded are resonance-excited and excluded from the ion trap 2. Note that the technique for removing ions in such a specific mass-to-charge ratio range from the ion trap is not limited to using an FNF signal. For example, a SWIFT (Stored Wave Inverse Fourier Transform) signal may be used instead of the FNF signal.

  In any case, after the operation for removing ions included in the specific mass-to-charge ratio range from the ion trap 2 is performed, the ions remaining in the ion trap 2 are cooled. Then, ions sufficiently converged by cooling are ejected from the ion trap 2 and introduced into the time-of-flight mass analyzer 3 for mass analysis. When the mass spectrum data obtained in this way is integrated with the previously obtained mass spectrum data, the intensity of the ion peak excluded from the measurement object does not increase as shown in FIG. Only the intensity of the ion peak increases.

  When the operation of removing a part of the ions trapped from the ion trap 2 is performed as described above, the amount of ions trapped in the ion trap 2 decreases. Therefore, the space charge density in the ion trap 2 is lowered, and the influence of the space charge on the spatial distribution and orbit of trapped ions is reduced. As a result, compared with the case where the space charge density in the ion trap 2 is high, mass accuracy and mass resolution are improved. In addition, since the loss of ions when ions are ejected from the ion trap 2 is reduced, the amount of ions used for mass analysis increases, leading to an improvement in detection sensitivity.

  The processes in steps S4 to S14 are repeated until the integration count value N matches the total integration count P. In the process, the mass to charge ratio range corresponding to the ion peak having a relatively high signal intensity is excluded from the mass to charge ratio range to be measured. Then, the mass-to-charge ratio range in which an ion peak having a low signal-to-noise ratio and a weak signal intensity is inevitably measured. As a result, it is possible to ensure a sufficient number of integrations for the ion peak having a weak signal intensity without causing waste of the sample and an increase in measurement time.

  FIG. 4 shows actual measurement results using the ion trap time-of-flight mass spectrometer of the present example. The actually measured sample was 50 [amol] peptide [Glu1] -Fibrinopeptide B (Glu-Fib) close to the detection limit of the apparatus, and the same measurement was performed 10 times on this sample. The horizontal axis of FIG. 4 is the number of times of the 10 trials, and the vertical axis is the intensity value of the detected Glu-Fib peak. In the figure, the plotted points indicated by ▲ are the results of the characteristic measuring method of the present embodiment described above, and the plotted points indicated by ● are the results of the normal measuring method performed with the same apparatus. Moreover, the average value of the result by 10 times of each measurement is also shown.

  FIG. 5 is an average mass spectrum obtained by the actual measurement shown in FIG. What is detected in the mass-to-charge ratio region of 1000 [Da] or less is an ion derived from a matrix, and a peak indicated by a downward arrow in the figure is a molecular ion peak of Glu-Fib. Note that, in order to make the measurement time conditions the same in the normal measurement method and the measurement method according to the present invention, the number of data integrations in both measurement methods was 640 times (that is, laser light irradiation was also 640 times).

  In the measurement method according to the present invention, data integration over the entire mass-to-charge ratio range is executed in the first half of the 640 repetitive measurements without removing ions from the ion trap 2 as in the normal measurement. Then, the measurement which excluded the ion derived from the matrix with relatively strong ion intensity from the ion trap came to be performed. Comparing with the average value of the peak intensities shown in FIG. 4, it can be confirmed that the measurement method according to the present invention is improved by about 1.8 times the S / N ratio over the normal measurement method. As described above, according to the measurement method characteristic of the present invention implemented by the ion trap time-of-flight mass spectrometer of the present embodiment described above, high detection sensitivity can be realized in the same measurement time as in the past.

  In the mass spectrum finally displayed in the above-described embodiment, there is a possibility that the signal intensity of each peak is for a substantially different number of integrations, and how many integrations are made for a certain peak. It is not known if the measurement is not actually performed. So, if you want to compare the signal intensity of different peaks on the same mass spectrum relatively or compare the signal intensity of peaks at the same mass to charge ratio on different mass spectra, for example, A peak list with a mass-to-charge ratio is obtained by performing peak picking processing and centroid processing on a continuous mass spectrum (peak profile) in the direction, and a signal corresponding to the number of integration is obtained for each peak included in the list. A correction process for correcting the intensity may be executed. As a result, relative comparison of peak intensities is possible without being affected by the difference in the number of integrations.

  In the above embodiment, the present invention is applied to a three-dimensional quadrupole ion trap, but a similar method can be used for a linear ion trap. However, in general, since the linear ion trap can capture a larger amount of ions than the three-dimensional quadrupole ion trap, the effect of space charge is less likely to be a problem. In this respect, the present invention is particularly useful for an ion trap mass spectrometer using a three-dimensional quadrupole ion trap.

  In the above embodiment, the ions discharged from the ion trap 2 are mass-separated by the time-of-flight mass analyzer 3 provided outside the ion trap 2 and detected by the ion detector 4. A configuration in which ions are discharged from the ion trap 2 in the order of the mass-to-charge ratio and detected by an external ion detector may be used by utilizing the mass separation function of the device itself.

  Furthermore, the above-described embodiment is an embodiment of the present invention, and it is also clear that any modification, change, addition or the like as appropriate within the scope of the present invention will be included in the scope of the claims of the present application. .

DESCRIPTION OF SYMBOLS 1 ... Ionization part 11 ... Sample plate 12 ... Sample 13 ... Laser irradiation part 14 ... Extraction electrode 2 ... Ion trap 21 ... Ring electrode 22 ... Inlet end cap electrode 23 ... Ion entrance 24 ... Outlet end cap electrode 25 ... Ion Injection port 3 ... Time-of-flight mass analyzer 4 ... Ion detector 5 ... Data processing unit 51 ... Spectral data collection unit 52 ... Spectral data integration unit 53 ... Peak SN ratio calculation unit 54 ... Peak SN ratio determination unit 55 ... Spectrum display Processing unit 6 Laser driving unit 7 Ion trap power supply unit 8 Control unit 81 Measurement condition setting unit 9 Operation unit 10 Display unit

Claims (3)

An ion source that generates ions in a packet form from a sample, and an ion trap that captures ions in a space surrounded by the electrodes, and the ions to be measured captured in the ion trap Ions that are separated and detected by the mass trap ratio by the ion trap itself, or ions that are to be measured are discharged from the ion trap and separated and detected by the mass analyzer provided outside the ion trap. In the trap mass spectrometer,
a) An ion peak having a relatively large influence on the space charge in the ion trap based on the result of performing mass analysis on the target sample over a predetermined mass-to-charge ratio range that is continuous or discontinuous by the apparatus. A peak identification part to be identified;
b) After trapping ions from the target sample in the ion trap, an operation of excluding ions in the mass-to-charge ratio range corresponding to the peak specified by the peak specifying unit from the ion trap is performed in the ion trap. A control unit for controlling the voltage applied to each of the plurality of electrodes constituting the ion trap so as to perform mass spectrometry on the remaining ions;
c) A processing unit that creates a final mass analysis result using results obtained by performing a plurality of mass analyzes on the target sample performed under the control of the control unit using the result of the peak specifying unit. When,
An ion trap mass spectrometer comprising: The ion trap mass spectrometer according to claim 1,
The peak specifying unit calculates an SN ratio of an ion peak appearing in a spectrum obtained by integrating data collected by mass spectrometry, and the influence on the space charge in the ion trap is relative based on the SN ratio. An ion trap mass spectrometer characterized by specifying a large ion peak. An ion source that generates ions in a packet form from a sample, and an ion trap that captures ions in a space surrounded by the electrodes, and the ions to be measured captured in the ion trap Ions that are separated and detected by the mass trap ratio by the ion trap itself, or ions that are to be measured are discharged from the ion trap and separated and detected by the mass analyzer provided outside the ion trap. A mass spectrometry method using a trap mass spectrometer,
Based on the result of performing mass analysis over a predetermined mass-to-charge ratio range that is continuous or non-continuous by the apparatus on the target sample, an ion peak that has a relatively large effect on the space charge in the ion trap is identified. Peak identification step;
After trapping ions from the target sample in the ion trap, an operation of removing ions in the mass-to-charge ratio range corresponding to the peak identified in the peak identifying step from the ion trap was performed and remained in the ion trap. A mass spectrometry step for performing mass spectrometry on the ions,
A mass characterized in that a final mass analysis result is created using a result obtained by performing mass analysis by the mass analysis step using the result of the peak specifying step a plurality of times for a target sample. Analysis method.

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