JP7468430B2 - Mass spectrometry apparatus and method - Google Patents

Description

The present invention relates to a mass spectrometer and a mass spectrometric method.

In the matrix-assisted laser desorption/ionization (MALDI) method, in order to analyze analytes that do not easily absorb laser light or that are easily damaged by laser light (e.g., objects made of proteins), a sample is prepared by mixing the analyte with a matrix that absorbs laser light and is more easily ionized than the analyte, and the sample is irradiated with laser light to ionize the analyte through the interaction between the analyte in the sample, the matrix, and the laser light. The MALDI method can analyze polymeric compounds with large molecular weights without causing much dissociation, and is also highly sensitive and suitable for trace analysis, so it has been widely used in fields such as life sciences in recent years.

In the MALDI method, samples are generally prepared by mixing a solution containing a matrix with the analyte, attaching the mixture to a sample plate, and drying the mixture (evaporating the solvent in the mixture). In samples prepared in this way, the analyte is not necessarily present uniformly throughout the sample, but may be unevenly distributed at specific locations. For this reason, a process has been performed in which a sample is irradiated with laser light, the ions generated are mass analyzed, and data (profile spectrum data) over a predetermined mass-to-charge ratio range is obtained by repeating this operation multiple times (e.g., tens to hundreds of times) while changing the irradiation position of the laser light on the sample, and the profile spectrum data obtained from these multiple measurements is accumulated to obtain mass spectrum data for the sample (see, for example, Patent Document 1).

JP 2014-212068 A ([0003]-[0006])

In this way, while acquiring profile spectrum data multiple times, pulse noise may occur due to sudden discharge, etc. In such a case, a peak due to pulse noise may occur only at a certain m/z (mass-to-charge ratio) in one of the multiple profile spectrum data. If the peak due to this pulse noise is similar to or smaller than the peak derived from the ions of the analyte, this will not be a problem because the single peak in the mass spectrum data obtained by accumulating multiple profile spectrum data will be relatively sufficiently smaller than the multiple accumulated peaks derived from the analyte. However, if the peak of the pulse noise is sufficiently larger than the peak of the ions of the analyte, the single peak in the accumulated mass spectrum data may be similar to the accumulated peak derived from the analyte. In such a case, it becomes difficult to distinguish whether the peak is derived from the pulse noise or from the ions of the analyte.

Here, we have used the MALDI method as an example, but when using mass spectrometry methods other than the MALDI method, the same problem occurs when accumulating multiple profile spectrum data to increase the S/N ratio.

The problem that the present invention aims to solve is to provide a mass spectrometer and a mass spectrometric method that can prevent the accumulation of profile spectrum data that includes the influence of noise when acquiring mass spectrum data by accumulating multiple profile spectrum data.

In order to solve the above problems, the mass spectrometer according to the present invention is
a measurement unit that performs k measurements (k is a natural number equal to or greater than 2) on one sample to obtain profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined range of mass-to-charge ratios;
a mass-to-charge ratio partial range setting unit for setting n partial ranges (n is a natural number of 2 or more) into which the range of mass-to-charge ratios is divided, each of the partial ranges including a plurality of mass-to-charge ratios;
a total ion intensity calculation unit that calculates a total ion intensity, which is the sum of the intensity values, for each of the n partial ranges for each of the k pieces of profile spectrum data acquired by the measurement unit;
and an outlier detection unit that performs a statistical test on the k total ion intensity values for each of the n partial ranges to detect outliers.

The mass spectrometry method according to the present invention comprises:
a measurement step of performing k measurements (k is a natural number equal to or greater than 2) on one sample to obtain profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined range of mass-to-charge ratios;
a mass-to-charge ratio partial range setting step of dividing the range of mass-to-charge ratios to set n partial ranges (n is a natural number of 2 or more), each of which includes a plurality of mass-to-charge ratios;
a total ion intensity calculation step of calculating a total ion intensity, which is a sum of the intensity values, for each of the n partial ranges for each of the k pieces of profile spectrum data acquired by the measurement step;
and an outlier detection step of performing a statistical test on the k total ion intensity values for each of the n partial ranges to detect outliers.

According to the present invention, the range of mass-to-charge ratios for which profile spectrum data is obtained is divided into n partial ranges, each of which includes a plurality of mass-to-charge ratios, and a total ion intensity is calculated as the sum of the intensity values for each mass-to-charge ratio. For each of the n partial ranges, a statistical test is performed on the total ion intensity values for k runs to detect outliers. If the profile spectrum data includes the effects of noise as described above, the total ion intensity of any of the partial ranges is detected as an outlier by the statistical test. Therefore, it is possible to prevent the accumulation of profile spectrum data including the effects of noise by excluding profile spectrum data including the partial ranges that are determined to be outliers and then halting the analysis when an outlier is detected.

1 is a schematic diagram showing an embodiment of a mass spectrometer according to the present invention; FIG. 2 is a schematic diagram showing the configuration of an MS/MS measurement condition setting unit of the mass spectrometer of the present embodiment. 4 is a flowchart showing the operation of the mass spectrometer of the present embodiment and an embodiment of a mass analysis method according to the present invention. 5 is a graph showing an example of noisy profile spectrum data obtained in this embodiment. FIG. 2 is an example of a table showing values of total ion intensities obtained in this embodiment, the table showing values of total ion intensities in each of five segments obtained from each of 25 sets of profile spectrum data. 6 is a table showing the results of the Smirnoff-Grubbs test performed on the example shown in FIG. 5. 4 is a graph showing an example of a mass spectrum obtained in this embodiment. 1 is a graph showing an example of a mass spectrum obtained in a comparative example.

Below, an embodiment of a mass spectrometry device and method according to the present invention will be described with reference to Figures 1 to 8.

(1) Configuration of the Mass Spectrometer of the Present Embodiment Fig. 1 shows the configuration of a MALDI mass spectrometer 1, which is one embodiment of the mass spectrometer of the present invention. This MALDI mass spectrometer 1 is a mass spectrometer that uses a MALDI ion source as an ion source and an ion trap type mass separator as a mass separator. The MALDI mass spectrometer 1 includes a MALDI mass analysis execution unit 10, a control and processing unit 20, an input unit 31, and a display unit 32.

The MALDI mass spectrometry execution unit 10 has a vacuum chamber 19 that is evacuated by a vacuum pump 191, and within this vacuum chamber 19, a sample stage 12 on which a sample plate 90 is placed, an extraction electrode 14, a quadrupole deflector 15, an ion trap 16, and an ion detector 17 are arranged.

Here, in order to show the positional relationship of each element of the MALDI mass spectrometry execution unit 10, three mutually orthogonal axes X, Y, and Z are defined for the sake of convenience, as shown in Figure 1. Typically, the X-Y plane is a plane parallel to the installation surface of the device, and the sample plate placement surface of the sample stage 12 is also parallel to the X-Y plane.

A transparent window 192 is provided on the wall (top) of the vacuum chamber 19 facing the top surface of the sample stage 12, and the laser light source 11 is disposed outside this window 192. The sample stage 12 can be moved freely in two axial directions, the X-axis and the Y-axis, by a stage drive unit 13 including a motor, etc.

The quadrupole deflector 15 consists of four rod electrodes extending in the Y-axis direction, and a deflection electric field that bends the direction of ion travel at approximately right angles in the space surrounded by the rod electrodes is formed by a DC voltage applied to each of the rod electrodes from a power source (not shown).

The ion trap 16 is a three-dimensional quadrupole configuration including a ring electrode 161 having a substantially circular shape, and an entrance end cap electrode 162 and an exit end cap electrode 164 arranged opposite each other across the ring electrode 161. An ion entrance hole 163 is formed in the entrance end cap electrode 162 located on the quadrupole deflector 15 side, and an ion exit hole 165 is formed in the exit end cap electrode 164. A predetermined voltage is applied to the ring electrode 161, the entrance end cap electrode 162, and the exit end cap electrode 164 from a power source (not shown), so that ions can be captured in the space surrounded by these electrodes, or ions can be ejected from the space through the ion exit hole 165.

The dissociation gas supply unit 18 supplies dissociation gas for collision induced dissociation (CID) into the ion trap 16 when performing MS/MS measurements.

The control/processing unit 20 has, as functional blocks, a measurement control unit 21, a data collection unit 22, a mass-to-charge ratio partial range setting unit 23, a total ion intensity calculation unit 24, an outlier detection unit 25, a mass spectrum data calculation unit 26, an MS/MS measurement condition setting unit 27, and a display control unit 28. The MS/MS measurement condition setting unit 27 has therein a peak detection unit 271, an ion identification unit 272, and an MS/MS measurement condition identification unit 273 (Figure 3).

The measurement control unit 21 controls each component included in the MALDI mass spectrometry execution unit 10 in order to perform measurements. The data collection unit 22 includes an analog-to-digital converter and a memory unit for storing data (neither shown), and digitizes the detection signal from the ion detector 17 and stores it in the memory unit as profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined mass-to-charge ratio range. The measurement control unit 21, data collection unit 22, and MALDI mass spectrometry execution unit 10 constitute the measurement unit.

Details of the mass-to-charge ratio partial range setting unit 23, total ion intensity calculation unit 24, outlier detection unit 25, mass spectrum data calculation unit 26, and MS/MS measurement condition setting unit 27 will be described later together with an explanation of the operation of the MALDI mass spectrometer 1 of this embodiment.

The display control unit 28 controls the display of an image on the display unit 32. The display control unit 28 also includes a warning display control unit 281 that controls the display unit 32 to display a warning when noise is present in the profile spectrum data obtained by the MALDI mass analysis execution unit 10. The warning display control unit 281 will be described in detail later. The warning display control unit 281 and the display unit 32 constitute a noise occurrence information notification unit, which will be described later.

In the control/processing unit 20, the above-mentioned functional blocks are realized by a computer such as a personal computer or a workstation and dedicated software installed on the computer. The input unit 31 is a keyboard and a pointing device attached to the computer, and the display unit 32 is a display monitor.

(2) Operation of the Mass Spectrometer of the Present Invention and the Mass Analysis Method of the Present Invention The operation of the MALDI mass analyzer 1 of the present invention and an embodiment of the mass analysis method according to the present invention will be described with reference to FIG.

First, a measurement is performed on the sample as follows (Step 1: Measurement process). First, a sample containing a mixture of an analyte and a matrix is attached to the surface of a sample plate 90, and the sample plate 90 is placed on the sample stage 12. Next, a vacuum is drawn inside the vacuum chamber 19 by the vacuum pump 191.

Measurement is then performed under the control of the measurement control unit 21. First, the sample stage 12 is moved in the XY direction by the stage driving unit 13 to place the sample on the surface of the sample plate 90 at a predetermined position, and the sample is irradiated with a laser beam from the laser light source 11 to ionize the analyte through the interaction between the analyte, the matrix, and the laser light. The generated ions are drawn upward from near the sample plate 90 by the electric field formed by the extraction electrode 14, and travel approximately in the Z-axis direction to reach the quadrupole deflector 15. The deflection electric field formed by the quadrupole deflector 15 bends the ion trajectory by approximately 90°. The ions then travel approximately in the X-axis direction, pass through the ion entrance hole 163, enter the internal space of the ion trap 16, and are temporarily captured by the electric field formed by the high-frequency voltage applied to the ring electrode 161. The ions are then ejected to the outside through the ion ejection hole 165 in ascending order of mass-to-charge ratio (or conversely, in ascending order of mass-to-charge ratio) by the electric field formed by the voltage applied to the entrance endcap electrode 162 and the exit endcap electrode 164. The ion detector 17 sequentially detects the ions ejected from the ion trap 16, and generates and outputs a detection signal corresponding to the amount of ions incident thereon. The data collection unit 22 receives and digitizes this detection signal, and stores it in the memory unit as profile spectrum data over a predetermined mass-to-charge ratio range.

When one measurement as described above is completed for one sample, the stage driver 13 moves the sample stage 12 slightly so that a different location on the same sample is brought to the measurement position. Then, a second measurement is performed in the same manner as described above, and this is repeated k times. The value of k is specified by the user using the input unit 31.

When k measurements are performed on one sample in this way, k pieces of profile spectrum data spanning a predetermined mass-to-charge ratio range are stored in the memory of the data acquisition unit 22. Note that since one piece of profile spectrum data consists of a group of data having many pieces of data with different mass-to-charge ratios, it can also be said that "k groups of data" are recorded in the memory.

In steps 2 and onwards, operations are performed to obtain a mass spectrum based on the profile spectrum data obtained in step 1. These operations are explained below with concrete examples.

In this specific example, profile spectrum data was acquired in the mass-to-charge ratio range of 520.68 to 5085.97, and 25 measurements (k=25) were performed on one sample. The 25 pieces of obtained profile spectrum data were numbered 0 to 24. Figure 4 shows the obtained profile spectrum data that includes noise. In the data of profile No. 24 shown in the lower part of Figure 4, pulse-like noise (pulse noise 1) is seen near m/z=1350, and in the data of profile No. 8 shown in the upper part of the figure, pulse-like noise (pulse noise 2) is seen near m/z=4800. Neither of these pulse noises 1 and 2 is seen in other profile spectrum data. These pulse noises 1 and 2 are several tens of times larger than the peaks originating from the original sample, so if a mass spectrum is created by directly accumulating the 25 pieces of profile spectrum data, the peaks originating from these pulse noises will have the same intensity as the peaks originating from the sample, and there is a risk that the peaks originating from the pulse noises will be mistaken for peaks originating from the sample. Therefore, in this embodiment, the following operations are performed.

First, in step 2 (mass-to-charge ratio partial range setting step), the mass-to-charge ratio partial range setting unit 23 sets n partial ranges (also called "segments") (n is a natural number of 2 or more) each including a plurality of mass-to-charge ratios, by dividing the above-mentioned predetermined mass-to-charge ratio range. In the above specific example, n=5, and the partial ranges are set as 520.68 to 1520.68 (called "segment 0"), 1520.68 to 2520.68 (segment 1), 2520.68 to 3520.68 (segment 2), 3520.68 to 4520.68 (segment 3), and 4520.68 to 5085.97 (segment 4). The value of n and the range of mass-to-charge ratio for each partial range are specified by the user using the input unit 31.

Next, in step 3 (total ion intensity calculation step), the total ion intensity calculation unit 24 calculates the sum (total ion intensity) of the intensity values obtained at the multiple m/z values in each of the n partial ranges for each of the k sets of profile spectrum data. Figure 5 shows in a table the total ion intensity values in each of the five partial ranges obtained for each of the 25 sets of profile spectrum data in the above specific example. The total ion intensity in segment 0 of profile No. 24, which is framed in a thick box in the figure, is higher than the total ion intensity in segment 0 of the profile spectrum data other than No. 24. Similarly, the total ion intensity in segment 4 of profile No. 8, which is framed in a thick box in the figure, is higher than the total ion intensity in segment 4 of the profile spectrum data other than No. 8. All of these correspond to the profile spectrum data and mass-to-charge ratios in which the above-mentioned pulse noise appears.

However, the total ion intensity of segment 4 of profile No. 8 in particular is not significantly different from segment 4 of other profile spectrum data, making it difficult for a user (person) to judge the presence or absence of noise by looking at this data. Therefore, a statistical test method is used. That is, the outlier detection unit 25 performs a statistical test on the total ion intensity values for k times for each of the n partial ranges to detect outliers of the total ion intensity, i.e., values outside a specified range (Step 4: Outlier detection process).

There are various known statistical testing methods, but in the above specific example, the Smirnov-Grubbs test, one of the most common methods for finding outliers, was used. The test results are shown in the table in Figure 6. In the figure, "FALSE" indicates that the total ion intensity was not determined to be an outlier, and "TRUE" indicates that the total ion intensity was determined to be an outlier. The total ion intensities of segment 0 of profile No. 24 and segment 4 of profile No. 8, which correspond to the profile spectrum data and mass-to-charge ratio in which pulse noise appeared, are determined to be "TRUE", i.e., outliers.

When an outlier is detected in step 4 (YES in step 5), the mass spectrum data calculation unit 26 calculates mass spectrum data by integrating the profile spectrum data excluding those in which the outlier detection unit 25 detected outliers among the k sets of profile spectrum data (step 6: mass spectrum data calculation step). In the above specific example, 23 sets of profile spectrum data excluding the data of profile Nos. 8 and 24 in which outliers were detected among the 25 sets of profile spectrum data are integrated. The mass spectrum obtained in this way is shown in FIG. 7. In addition, as a comparative example, a mass spectrum obtained by integrating 25 sets of profile spectrum data including the data of profile Nos. 8 and 24 is shown in FIG. 8. In FIG. 8, two peaks corresponding to pulse noises 1 and 2 are seen in the mass spectrum, whereas in FIG. 7, these two peaks are not seen. In this way, a mass spectrum in which the effects of pulse noises 1 and 2 are eliminated can be obtained by this embodiment.

When the outlier detection unit 25 detects an outlier, it transmits an outlier detection signal to the warning display control unit 281 in the display control unit 28. When the warning display control unit 281 receives the outlier detection signal, it controls the display unit 32 to display a warning indicating that noise has occurred (step 7: noise occurrence information notification process). The warning displayed on the display unit 32 may be text or a figure. It may also be possible to simply display the occurrence of noise, but since the occurrence of noise may indicate that dirt has adhered to the inside of the vacuum chamber 19 or that some kind of malfunction has occurred in the device, a display may be displayed to prompt maintenance. In addition to or instead of displaying by the warning display control unit 281, when the outlier detection unit 25 detects an outlier, the fact may be recorded in a log file.

On the other hand, if no outliers are detected in step 4 (NO in step 5), the mass spectrum data calculation unit 26 calculates mass spectrum data by integrating all of the k sets of profile spectrum data (step 6': mass spectrum data calculation process).

If the answer is YES in step 5, then after steps 6 and 7, and if the answer is NO in step 5, then after step 6', the display control unit 28 controls the display unit 32 to display the mass spectrum based on the mass spectrum data obtained by the mass spectrum data calculation unit 26. This causes the mass spectrum to be displayed on the display unit 32 (step 8: mass spectrum display process).

In this embodiment, the MS/MS measurement condition setting unit 27 sets the conditions for performing the MS/MS measurement based on the mass spectrum data calculated by the mass spectrum data calculation unit 26 as follows (step 9: MS/MS measurement condition setting process). First, the peak detection unit 271 detects mass spectrum peaks from the mass spectrum data calculated by the mass spectrum data calculation unit 26. Next, the ion identification unit 272 obtains the mass-to-charge ratio values at which the peaks detected by the peak detection unit 271 appear, and identifies the ions corresponding to those mass-to-charge ratios. The MS/MS measurement condition identification unit 273 uses the ions identified by the ion identification unit 272 as precursor ions and identifies the conditions for performing the MS/MS measurement corresponding to the precursor ions, such as the type of gas supplied from the dissociation gas supply unit 18 and the voltage applied to each electrode. In order for the ion identification unit 272 to identify ions and for the MS/MS measurement condition identification unit 273 to identify the conditions for executing MS/MS measurement, the MS/MS measurement condition setting unit 27 has a memory unit that stores the correspondence between mass-to-charge ratios and ions (precursor ions) and the conditions for executing MS/MS measurement for each precursor ion.

Based on the conditions set in this way, the measurement control unit 21 performs MS/MS measurement (step 10), and when the MS/MS measurement is finished, the series of operations is completed.

(3) Modifications The present invention is not limited to the above-described embodiment, and various modifications are possible.

In the above embodiment, the Smirnoff-Grubbs test was used to find outliers, but other statistical testing methods such as the Thompson test may also be used.

In the above embodiment, the MS/MS measurement condition setting unit 27 may be omitted, and the user may input the conditions for the MS/MS measurement from the input unit 31 based on the mass spectrum displayed on the display unit 32. Also, if no MS/MS measurement is performed, the dissociation gas supply unit 18 may be omitted together with the MS/MS measurement condition setting unit 27.

In the above embodiment, when a noise peak is present in the k pieces of profile spectrum data, a warning is displayed on the display unit (display monitor) 32. However, instead, a warning may be issued by sounding a buzzer or turning on a lamp, etc. Also, issuing such a warning is not essential, and the warning display control unit 281 may be omitted.

In the above embodiment, when a noise peak is present in part of the k pieces of profile spectrum data, the mass spectrum is calculated by integrating the profile spectrum data excluding the profile spectrum data containing the noise peak. However, when such a noise peak is present, it is also possible to issue only a warning without calculating the mass spectrum.

In the above embodiment, an ion trap mass separator is used, but other mass separators such as a time-of-flight mass separator may also be used.

The above embodiment was directed to a MALDI mass spectrometer, but the present invention can also be applied to other mass spectrometers.

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

(Section 1)
The mass spectrometer according to paragraph 1,
a measurement unit that performs k measurements (k is a natural number equal to or greater than 2) on one sample to obtain profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined range of mass-to-charge ratios;
a mass-to-charge ratio partial range setting unit for setting n partial ranges (n is a natural number of 2 or more) into which the range of mass-to-charge ratios is divided, each of the partial ranges including a plurality of mass-to-charge ratios;
a total ion intensity calculation unit that calculates a total ion intensity, which is the sum of the intensity values, for each of the n partial ranges for each of the k pieces of profile spectrum data acquired by the measurement unit;
and an outlier detection unit that performs a statistical test on the k total ion intensity values for each of the n partial ranges to detect outliers.

(Section 6)
The mass spectrometry method according to claim 6 comprises:
a measurement step of performing k measurements (k is a natural number equal to or greater than 2) on one sample to obtain profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined range of mass-to-charge ratios;
a mass-to-charge ratio partial range setting step of dividing the range of mass-to-charge ratios to set n partial ranges (n is a natural number of 2 or more), each of which includes a plurality of mass-to-charge ratios;
a total ion intensity calculation step of calculating a total ion intensity, which is a sum of the intensity values, for each of the n partial ranges for each of the k pieces of profile spectrum data acquired by the measurement step;
and an outlier detection step of performing a statistical test on the k total ion intensity values for each of the n partial ranges to detect outliers.

According to the mass spectrometer according to paragraph 1 and the mass spectrometric method according to paragraph 6, the range of mass-to-charge ratios for which profile spectrum data is obtained is divided into n partial ranges, each of which includes a plurality of mass-to-charge ratios, and a total ion intensity is calculated as the sum of the intensity values for each mass-to-charge ratio. For each of the n partial ranges, a statistical test is performed on the total ion intensity values for k runs to detect outliers. If the profile spectrum data includes the effects of noise as described above, the total ion intensity of any of the partial ranges is detected as an outlier by the statistical test. Therefore, it is possible to prevent the accumulation of profile spectrum data including the effects of noise by excluding profile spectrum data including the partial ranges that are determined to be outliers and performing the accumulation to obtain a mass spectrum, or by stopping the analysis when an outlier is detected.

If outliers in intensity for each mass-to-charge ratio are detected instead of outliers in total ion intensity for each partial range, there is a risk that a peak derived from a sample that appears at a position slightly shifted from the original mass-to-charge ratio for some reason may be erroneously detected as noise. In contrast, in the mass spectrometer according to paragraph 1 and the mass spectrometric method according to paragraph 6, a statistical test is performed using partial ranges containing multiple mass-to-charge ratios as a unit, so that even if a peak derived from a sample that is slightly shifted from the original mass-to-charge ratio is included, it is not considered an outlier in the partial range unit, and erroneous detection can be prevented.

(Section 2)
The mass spectrometer according to paragraph 2 is the mass spectrometer according to paragraph 1, further comprising a mass spectrum data calculation unit that acquires mass spectrum data by integrating profile spectrum data excluding the profile spectrum data in which the outlier was detected from the k pieces of profile spectrum data.

The mass spectrometer according to paragraph 2 can obtain mass spectrum data that is free of the effects of noise contained in multiple (k) sets of profile spectrum data by integrating the profile spectrum data excluding profile spectrum data in which outliers have been detected.

(Section 3)
The mass spectrometer according to paragraph 3 further comprises the mass spectrometer according to paragraph 2,
a peak detection unit that detects a peak of a mass spectrum based on the mass spectrum data acquired by the mass spectrum data calculation unit;
an ion identification unit that determines a mass-to-charge ratio at which a peak detected by the peak detection unit appears and identifies an ion corresponding to the mass-to-charge ratio;
and an MS/MS measurement condition specifying unit that specifies conditions for performing an MS/MS measurement corresponding to the precursor ion, using the ion specified by the ion specifying unit as the precursor ion.

According to the mass spectrometer of paragraph 3, an ion is identified based on the mass spectrum data acquired by the mass spectrum data calculation unit, and MS/MS measurement is performed based on the measurement conditions in which the ion is identified as a precursor ion. Therefore, the MS/MS measurement can be performed easily and reliably without requiring the user to do anything, and the effects of noise can be removed.

(Section 4)
The mass spectrometer according to paragraph 4 is the apparatus according to any one of paragraphs 1 to 3, further comprising a noise occurrence information notification unit that notifies a user of noise occurrence information indicating the occurrence of noise when the outlier detection unit detects an outlier.

According to the mass spectrometer of paragraph 4, when the outlier detection unit detects an outlier, it notifies the user of noise occurrence information, so that the user can know that noise has occurred. Examples of noise occurrence information include sound (buzzer, voice, etc.), light, or characters or figures displayed on a screen.

A mass spectrometer according to paragraph 4 that cites paragraph 2 notifies the user of noise occurrence information and also acquires mass spectrum (outlier-removed mass spectrum) data by accumulating profile spectrum data excluding profile spectrum data in which outliers are detected in the mass spectrum data calculation unit. The outlier-removed mass spectrum may be displayed on the screen of the display unit together with a warning (or without displaying a warning on the screen), or, depending on a selection operation by the user, either or both of the outlier-unremoved profile spectrum (accumulated including profile spectrum data in which outliers are detected) and the outlier-removed mass spectrum may be displayed. Alternatively, since noise occurrence may indicate some abnormality in the mass spectrometer, the mass spectrometer may only notify the user of noise occurrence information without acquiring mass spectrum data (a mass spectrometer according to paragraph 4 that does not cite paragraph 2).

(Section 5)
A mass spectrometer according to a fifth aspect is the mass spectrometer according to the fourth aspect, wherein the noise occurrence information includes information prompting the execution of maintenance.

The mass spectrometer according to paragraph 5 notifies the user with information (text, audio, etc.) urging the user to perform maintenance, and when the user receives this information and performs the maintenance, mass analysis can be performed normally thereafter.

Reference Signs List 1...MALDI mass spectrometer 10...MALDI mass analysis execution unit 11...Laser light source 12...Sample stage 13...Stage drive unit 14...Extraction electrode 15...Quadrupole deflector 16...Ion trap 161...Ring electrode 162...Inlet end cap electrode 163...Ion entrance hole 164...Outlet end cap electrode 165...Ion exit hole 17...Ion detector 18...Dissociation gas supply unit 19...Vacuum chamber 191...Vacuum pump 192...Vacuum chamber window 20...Control and processing unit 21...Measurement control unit 22...Data collection unit 23...Mass-to-charge ratio partial range setting unit 24...Total ion intensity calculation unit 25...Outlier detection unit 26...Mass spectrum data calculation unit 27...MS/MS measurement condition setting unit 271...Peak detection unit 272...Ion identification unit 273...MS/MS measurement condition identification unit 28...Display control unit 281...Warning display control unit 31...Input unit 32...Display unit

Claims (6)

a measurement unit that performs k measurements (k is a natural number equal to or greater than 2) on one sample to obtain profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined range of mass-to-charge ratios;
a mass-to-charge ratio partial range setting unit for setting n partial ranges (n is a natural number of 2 or more) into which the range of mass-to-charge ratios is divided, each of the partial ranges including a plurality of mass-to-charge ratios;
a total ion intensity calculation unit that calculates a total ion intensity, which is the sum of the intensity values, for each of the n partial ranges for each of the k pieces of profile spectrum data acquired by the measurement unit;
an outlier detection unit that performs a statistical test on the total ion intensity values for the k runs for each of the n partial ranges to detect outliers. The mass spectrometer according to claim 1, further comprising a mass spectrum data calculation unit that acquires mass spectrum data by integrating the profile spectrum data excluding the profile spectrum data in which the outlier is detected from the k pieces of profile spectrum data. moreover,
a peak detection unit that detects a peak of a mass spectrum based on the mass spectrum data acquired by the mass spectrum data calculation unit;
an ion identification unit that determines a mass-to-charge ratio at which a peak detected by the peak detection unit appears and identifies an ion corresponding to the mass-to-charge ratio;
3. The mass spectrometer according to claim 2, further comprising: an MS/MS measurement condition specifying unit that specifies conditions for performing an MS/MS measurement corresponding to the precursor ion identified by the ion identifying unit, using the precursor ion as the precursor ion. The mass spectrometer according to any one of claims 1 to 3, further comprising a noise occurrence information notification unit that notifies a user of noise occurrence information indicating the occurrence of noise when the outlier detection unit detects an outlier. The mass spectrometer according to claim 4, wherein the noise occurrence information includes information prompting the execution of maintenance. a measurement step of performing k measurements (k is a natural number equal to or greater than 2) on one sample to obtain profile spectrum data consisting of ion intensity values for each mass-to-charge ratio within a predetermined range of mass-to-charge ratios;
a mass-to-charge ratio partial range setting step of dividing the range of mass-to-charge ratios to set n partial ranges (n is a natural number of 2 or more), each of which includes a plurality of mass-to-charge ratios;
a total ion intensity calculation step of calculating a total ion intensity, which is a sum of the intensity values, for each of the n partial ranges for each of the k pieces of profile spectrum data acquired by the measurement step;
and an outlier detection step of performing a statistical test on the total ion intensity values for the k runs for each of the n partial ranges to detect outliers.

Images