WO2023017558A1

WO2023017558A1 - Mass spectrometry assistance method, mass spectrometry assistance device, and mass spectrometry system

Info

Publication number: WO2023017558A1
Application number: PCT/JP2021/029492
Authority: WO
Inventors: 拓也吉本; 司師子鹿; 俊幸檜山
Original assignee: 株式会社日立ハイテク
Priority date: 2021-08-10
Filing date: 2021-08-10
Publication date: 2023-02-16
Also published as: JPWO2023017558A1

Abstract

To enable mass spectrometry using simple operations, this invention is characterized by comprising a storage unit (120) having a plurality of scan speeds stored thereon in advance as a scan speed pattern, an acquisition unit for acquiring a first mass spectrum that is the result of measurement by a mass spectrometry device (200), and a scan speed variation processing unit that, when an enlarged range or reduced range of the first mass spectrum displayed on a display unit is designated by a user, acquires the m/z range of the enlarged range or reduced range, selects the scan speeds stored in the scan speed pattern in order, uses a mass spectrometry device to carry out provisional measurement of the m/z range of the enlarged range or reduced range at the selected scan speeds, and determines a scan speed for the m/z range of the enlarged range or reduced range on the basis of second mass spectrums obtained as a result of the provisional measurement.

Description

Mass spectrometry support method, mass spectrometry support device, and mass spectrometry system

The present invention relates to techniques for mass spectrometry support methods, mass spectrometry support devices, and mass spectrometry systems.

　It is very difficult for users with little knowledge of mass spectrometry to use mass spectrometers. Moreover, even if the user has sufficient knowledge about the mass spectrometer, it is extremely difficult to comprehensively learn and use all the functions of the software of the mass spectrometer.

Also, from the viewpoint of usability, it is desirable that any user can perform certain operations through the presented graphical user interface (GUI), regardless of whether or not they have knowledge of mass spectrometry.

For example, the GUI of the mass spectrometer displays a mass spectrum, which is the relationship between the m/z value and the detected ion intensity. The mass spectrum is obtained by scanning the m/z range to be measured by the mass spectrometer at a predetermined scan speed, plotting the ion intensity corresponding to the amount of ions detected on the vertical axis and the m/z corresponding to the ion on the horizontal axis. It is the graph which displayed the value.

As an invention related to the operation of such a mass spectrometer, Patent Document 1 describes "Even in a device with little information obtained from the mass spectrum of MS ¹ analysis such as LC / MS using the atmospheric pressure ionization method, it can be accurately and quickly A mass spectrometry method and apparatus are disclosed (see Abstract).

In addition, in Patent Document 2, "MS analysis of each minute area within the specified mass spectrometry range on the sample is performed, and based on the data obtained, the specified m / z or m / z range is created and displayed on the display screen (S10 to S14), the operator identifies the substance of interest and designates its m/z (S15), and the m/z is displayed on the MS spectrum. A microregion whose intensity is equal to or greater than a threshold value is extracted, and MS/MS analysis is performed on the microregion using the m/z of the substance of interest as a precursor (S26, S27). An average MS/MS spectrum is calculated from the /MS spectrum data (S28), and identification of a substance of interest is performed using peak information appearing in the average MS/MS spectrum (S19). (see summary).

JP-A-2001-249114 WO2010/001439

The designation of the m/z range and scanning speed is generally fixed in advance, and in some cases, such as the technique described in Patent Document 1, the user edits and designates a text box or the like.
However, with these methods, it is difficult to change the m/z range and scan speed if the user does not have knowledge of mass spectrometry, or if the user does not know the position of the text box on the GUI screen. Become.

The present invention has been made in view of such a background, and an object of the present invention is to enable mass spectrometry to be performed with a simple operation.

In order to solve the above-described problems, the present invention provides a mass spectrum acquisition step in which a computing device acquires a first mass spectrum that is a result of measurement by a mass spectrometer; an m/z range obtaining step of obtaining an m/z range of the expanded range or the reduced range when the expanded range or the reduced range of one mass spectrum is specified; and the scan speed stored in the scan speed pattern. are sequentially selected, temporary measurement is performed on the m / z range at the selected scan speed, and the scan speed is determined based on the second mass spectrum obtained as a result of the temporary measurement. and are performed.
Other solutions will be described as appropriate in the embodiments.

According to the present invention, mass spectrometry can be performed with easy operation

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure which shows the structural example of the mass spectrometry system which concerns on 1st Embodiment. It is a figure which shows the structural example of the process part in an arithmetic unit. It is a figure which shows the structural example of a memory|storage part. It is a figure which shows an example of the hardware constitutions of an arithmetic unit. 4 is a flowchart showing the procedure of overall processing according to the first embodiment; FIG. 5 is a diagram showing an example of a scan speed setting screen in the first embodiment; FIG. It is a figure which shows the mass spectrum before an expansion process. It is a figure which shows an example of the mass spectrum after an expansion process. FIG. 10 is a diagram showing a detailed processing procedure of scan speed change processing; 1 is a diagram (1) showing an example of a mass spectrum obtained by provisional measurement; FIG. FIG. 2 is a diagram (part 2) showing an example of a mass spectrum obtained by provisional measurement; FIG. 3 is a diagram (part 3) showing an example of a mass spectrum obtained by provisional measurement; It is a figure which shows an example of the mass spectrum before an expansion process. An example of a mass spectrum under expansion processing is shown.

A mode for carrying out the present invention will be described with reference to the drawings. It should be noted that the embodiments of the present invention are not limited to the examples shown here.

<First embodiment>
In a first embodiment, the user magnifies the mass spectrum M1 (see FIG. 7A) and stores the m/z range to measure. After that, the arithmetic device 100 performs processing to change the scanning speed according to the m/z range.

[Configuration of mass spectrometry system Z]
FIG. 1 is a diagram showing a configuration example of a mass spectrometry system Z according to the first embodiment.
The mass spectrometry system Z includes an arithmetic device 100 , a mass spectrometer 200 and a sample supply device 300 .
The computing device 100 has a display unit 101 , an input unit 102 , a processing unit 110 and a storage unit 120 .
The processing unit 110 and the storage unit 120 will be described later.
The display unit 101 displays a mass spectrum M (see FIGS. 7A and 7B), which is the result of measurement by the mass spectrometer 200, and the like.
The input unit 102 is a keyboard, a mouse, or the like, through which information is input by the user.

The sample supply device 300 supplies sample components to the mass spectrometer 200 . For example, the sample supply device 300 is a liquid chromatograph, a gas chromatograph, or a device that heats a sample to vaporize components.

The mass spectrometer 200 includes an ionization section 201 , a mass separation section 202 , an ion detection section 203 and a control section 210 .
The ionization section 201 ionizes the sample component supplied from the sample supply device 300 .
The mass separation unit 202 selects fragmentation of ions supplied from the ionization unit 201 , ion trap, and specific m/z values to be discharged to the ion detection unit 203 , and sends the ions to the ion detection unit 203 . The mass separation unit 202 can be configured with a single mass, MS/MS, MS ⁿ in which three or more stages of MS are connected, or the like.
The ion detector 203 measures the ion intensity of ions sent from the mass separator 202 .

The control unit 210 performs control to update the m/z range to be measured and change the scan speed according to instructions from the arithmetic device 100 . Then, the ion intensity data corresponding to the m/z value is returned to the computing device 100 .

Note that the m / z value selected by the mass separation unit 202 is fixed, and the change in ion intensity over time, that is, the chromatogram is obtained by selected ion monitoring (SIM) or selected reaction monitoring (Selected Reaction Monitoring: SRM). ) is a quantitative measurement called

(Processing unit 110)
FIG. 2 is a diagram showing a configuration example of the processing unit 110 in the arithmetic device 100 (see FIG. 1).
The processing unit 110 has an acquisition unit 111 , a scan speed change processing unit 112 and a display processing unit 113 .
The acquisition unit 111 acquires measurement results (mass spectrum information) and the like from the mass spectrometer 200 .
The scan speed change processing unit 112 determines an appropriate scan speed for the mass spectrometer 200 (determines the scan speed used for measurement) based on the enlargement or reduction processing of the mass spectrum M1 (see FIG. 7A) by the user. Then, the scan speed change processor 112 sets the determined scan speed in the mass spectrometer 200 . In this embodiment, the mass spectrum to be scaled is distinguished as a mass spectrum M1, and a mass spectrum M is used when mass spectra are generally indicated. Here, an appropriate scanning speed means a scanning speed at which a mass spectrum M with excellent resolution can be obtained. If the scanning speed is too fast or too slow, the resolution will decrease.
The display processing unit 113 displays the mass spectrum M (see FIGS. 7A and 7B), the scan speed setting screen 400 (see FIG. 6), and the like on the display unit 101 .

In this embodiment, the functions of the processing unit 110 are provided in the arithmetic device 100, which is a device different from the mass spectrometer 200, but the functions of the processing unit 110 are provided in the control unit 210 of the mass spectrometer 200. may be provided.

(storage unit 120)
FIG. 3 is a diagram showing a configuration example of the storage unit 120. As shown in FIG.
A scan speed pattern 121 and a change m/z range 122 are stored in the storage unit 120 .
The scan speed pattern 121 stores a plurality of scan speeds for each m/z range, which are used in provisional measurements described later.
The changed m/z range 122 is the m/z range changed by enlargement or contraction processing of the mass spectrum M1 (see FIG. 7A), which will be described later. As will be described later, since the expansion or contraction processing of the mass spectrum M1 is performed by the input unit 102, the changed m/z range 122 is stored in the storage unit 120 from the input unit 102.

Also, the scan speed change processing unit 112 selects a scan speed for temporary measurement, which will be described later, by referring to the change m/z range 122 and the scan speed pattern 121 .

[Hardware Configuration of Arithmetic Device 100]
FIG. 4 is a diagram showing an example of the hardware configuration of the arithmetic device 100. As shown in FIG.
The arithmetic device 100 has a memory 131, a CPU (Central Processing Unit) 132, and a storage device 133 such as an HD (Hard Disk) or an SSD (Solid State Disk). The computing device 100 also has an input device 134 such as a keyboard and a mouse, a display device 135 such as a display, and a communication device 136 .
A program is stored in the storage device 133 and loaded into the memory 131 . The loaded program is then executed by the CPU 132 . As a result, the processing unit 110 in FIG. 2, the acquisition unit 111 constituting the processing unit 110, the scan speed change processing unit 112, and the display processing unit 113 are embodied.
Incidentally, the input device 134 corresponds to the input section 102 in FIG. 1, the display device 135 corresponds to the display section 101 in FIG. 1, and the storage device 133 corresponds to the storage section 120 in FIG.

[Overall processing]
FIG. 5 is a flowchart showing the procedure of overall processing according to the first embodiment. Reference will be made to FIGS. 1 to 3 as appropriate.
First, the user sets the scan speed on the scan speed setting screen 400 (see FIG. 6) (S1). Here, it is assumed that Auto 402 (see FIG. 6) is set. Note that the scan speed setting screen 400 will be described later.

Subsequently, measurement is performed by the mass spectrometer 200 (S2), and the acquisition unit 111 of the arithmetic device 100 acquires mass spectrum information, which is the result of the measurement (S3). Note that the scanning speed and m/z range used in the measurement performed in step S2 are automatically set by the control unit 210. FIG.
Then, the display processing unit 113 displays the mass spectrum M1 (see FIG. 7A) on the display unit 101 based on the obtained mass spectrum information.

Next, the scan speed change processing unit 112 determines whether or not enlargement/reduction processing of the mass spectrum M1 displayed on the display unit 101 has been executed via the input unit 102 (S4). The enlargement/reduction processing will be described later.
If the enlargement/reduction process has not been executed (S4→No), the scan speed change processing unit 112 returns the process to step S4.

When the scaling process is executed (S4→Yes), the scan speed change processing unit 112 changes the m/z range (changed m/z range 122) in the scaled or reduced mass spectrum M (see FIGS. 7A and 7B). is obtained and stored in the storage unit 120 (S5). The processing of step S5 will be described later. That is, the processing from step S5 onwards is executed when the enlargement execution processing of step S4 is performed.

Then, the scan speed change processing unit 112 calculates an appropriate scan speed based on the changed m/z range 122 stored in the storage unit 120, and sets the calculated scan speed in the control unit 210 of the mass spectrometer 200. Speed change processing is performed (S6). The processing of step S6 will be described later. In step S<b>6 , the scan speed change processing unit 112 determines an appropriate scan speed for the change m/z range 122 and sets the determined scan speed in the control unit 210 .
Next, the control unit 210 starts measuring the measurement object at the scanning speed set in step S6 (S7).

[Scan speed setting screen 400]
FIG. 6 is a diagram showing an example of the scan speed setting screen 400 in the first embodiment. A scan speed setting screen 400 shown in FIG. 6 is displayed on the display unit 101 at the stage of step S1 in FIG.
The scan speed setting screen 400 allows the user to set the scan speed. The user can set Narrow Range 401 , Auto 510 and Full Range 403 on the scan speed setting screen 400 .
When Narrow Range 401 is selected, scanning is performed at low speed in mass spectrometry. When Auto 402 is selected, the scan speed is automatically changed according to the change m/z range 122 (see FIG. 3) determined by the user's scaling process. When Full Range 403 is selected, scanning is performed at high speed in mass spectrometry. This embodiment (scanning speed change processing step for determining the scanning speed) is processing performed when Auto 402 is selected. Note that Narrow Range 401 may become unusable, but in this case, Narrow Range 401 is grayed out and cannot be selected.

After the user selects one of Narrow Range 401, Auto 403, and Full Range 403, the selection is confirmed by selecting and inputting the OK button 411. Also, the selection is canceled by selecting and inputting the cancel button 412 .

[Enlargement/reduction process]
Next, the enlargement/reduction processing in step S4 of FIG. 5 will be described with reference to FIGS. 7A and 7B. Although the enlargement process is described with reference to FIGS. 7A and 7B, the reduction process can also be performed using the same procedure.

FIG. 7A is a diagram showing a mass spectrum M1 before expansion processing.
In addition, in FIG. 7A and FIG. 7B, the horizontal axis is the m/z value, and the horizontal axis is the ion intensity (Intensity).
The user selects the expansion range 500 by dragging from the start point 501 to the end point 502 .
For example, the user presses a left click at an arbitrary position in the mass spectrum M1 presented on the display device 135 to set the starting point 501 there. After that, in the mass spectrum M1, the user moves the mouse while pressing the click to an arbitrary position to be measured, releases the click button, and sets the end point 502 there.

The m/z range indicated by symbol R corresponding to the base of the expanded range 500 is the expanded m/z range (changed m/z range 122).

By such operation, a new m/z range (changed m/z range 122) is stored in the storage unit 120 based on the coordinates of the start point 501 and the end point 502 in the mass spectrum M1. Then, the scan speed change processing unit 112 reads the changed m/z range 122 stored in the storage unit 120 .
The scan speed change processing unit 112 selects the scan speed saved in the scan speed pattern 121 based on the read change m/z range 122 . Then, the scan speed change processing unit 112 repeats temporary measurement at the selected scan speed and determines an appropriate scan speed. A method for determining an appropriate scanning speed will be described later. Furthermore, the scan speed change processing unit 112 determines a high frequency voltage corresponding to the determined scan speed. The scan speed change processing unit 112 sets the determined high-frequency voltage and the change m/z range 122 in the control unit 210 . Incidentally, the scan speed is controlled by controlling the high frequency voltage applied to the mass separator 202 .

FIG. 7B is a diagram showing an example of the mass spectrum M2 after expansion processing.
In FIG. 7B, the scan speed change processing unit 112 updates the m/z range based on the expanded range 500 selected in FIG. It is shown. That is, the mass spectrum M2 shown in FIG. 7B is the result of measurement at the scan speed determined by the scan speed change processor 112 based on the expanded range 500 (see FIG. 7A). Therefore, the mass spectrum M2 differs in shape from the mass spectrum M1 shown in FIG. 7A. The mass spectrum M2 differs in shape from the mass spectrum M1 shown in FIG. 7A because of the difference in scanning speed.

Incidentally, the m/z range of the mass spectrum M2 shown in FIG. 7B is the m/z range indicated by symbol R in FIG. 7A.

The mass spectrum M2 shown in FIG. 7B has deeper valleys between the peaks than the mass spectrum M1 shown in FIG. 7A because it has undergone each step of the scan speed changing process and is measured at an appropriate scan speed. That is, the mass spectrum M2 is in a state in which the isotope components that could not be confirmed in the mass spectrum M1 due to the problem of mass resolution are separated, making it easier for the user to confirm the isotope components.

[Scan speed change processing]
Next, the scanning speed changing process in step S6 of FIG. 5 will be described with reference to FIGS. 8 and 9A to 9C.

(flowchart)
FIG. 8 is a diagram showing detailed processing procedures of the scan speed changing process in step S6 of FIG.
First, the scan speed change processing unit 112 acquires expanded mass spectrum information or reduced mass spectrum information (referred to as changed mass spectrum information) based on step S4 (enlargement/reduction processing) in FIG. 5 (S601).
Then, the scan speed change processing unit 112 determines whether the mass spectrum M based on the acquired changed mass spectrum information (see FIGS. 7A and 7B; hereinafter referred to as a changed mass spectrum) satisfies the following conditions. (S602).
(Condition #1) There are at least two peaks in the modified mass spectrum.
(Condition #2) In the modified mass spectrum, the maximum ion intensity at the second largest peak is greater than 50% when the maximum ion intensity is taken as 100%.
Note that if both the condition #1 and the condition #2 are satisfied, the scan speed change processing unit 112 determines "Yes" in step S602.

If the condition #1 or condition #2 is not satisfied (S602→No), the scan speed change processing unit 112 terminates the process.
If condition #1 and condition #2 are satisfied (S602→Yes), scan speed change processing unit 112 reads scan speed pattern 121 from storage unit 120 (S611). As described above, in the scan speed pattern 121, a plurality of scan speeds are set in advance for performing temporary measurements, which will be described later.
Next, the scan speed change processing unit 112 selects one scan speed from the scan speed pattern 121 (S612). At this time, the scan speed change processing unit 112 selects a scan speed that is not used for temporary measurement, which will be described later. Also, as described above, the scan speed pattern 121 stores a plurality of scan speeds for each change m/z range 122 . Therefore, the scan speed change processing unit 112 selects one scan speed from the scan speeds assigned to the m/z range (changed m/z range 122) in the changed mass spectrum acquired in step S601.

Then, the scan speed change processor 112 sets the scan speed selected in step S612 to the controller 210 of the mass spectrometer 200 (S613).
After that, the control unit 210 measures the measurement object in the changed m/z range 122 at the set scanning speed. This is called provisional measurement. That is, the control unit 210 performs temporary measurement in the changed m/z range 122 at the set scan speed (S614). The temporary measurement results (specifically, the mass spectrum M (FIGS. 7A and 7B)) are sent to the computing device 100 and stored in the storage unit 120 .
Subsequently, the scan speed change processing unit 112 determines whether provisional measurement has been completed at all scan speeds assigned to the change m/z range 122 in the scan speed pattern 121 (S621).
If provisional measurement has not been completed at all scan speeds (S621→No), the scan speed returns to step S612.

If provisional measurements have been completed at all scan speeds (S621→Yes), the scan speed change processing unit 112 compares the results of provisional measurements for each scan speed (S631). At this time, the scan speed change processing unit 112 compares the ion intensity at the deepest point in the temporary measurement result (mass spectrum M). A comparison of the temporary measurement results will be described later.

Subsequently, the scan speed change processing unit 112 determines the scan speed (used for measurement) based on the result of step S631 (S632). A method of determining the scanning speed will be described later.
Then, the scan speed change processing unit 112 sets the scan speed determined in step S632 as an appropriate scan speed for the change m/z range 122 in the control unit 210 (S633).

(Specific example of scan speed change processing)
Next, specific processing of the scan speed change processing shown in FIG. 8 will be described with reference to FIGS. 9A to 9C. Note that FIGS. 9A to 9C describe scan speed change accompanying enlargement processing of mass spectrum M (see FIGS. 7A and 7B), but similar processing can be applied to scan speed change accompanying reduction processing. is.
First, as shown in FIG. 7A, the scan speed change is triggered by the user performing enlargement processing (or reduction processing) from the state in which the entire mass spectrum M1 is displayed. That is, when the expansion range 500 shown in FIG. 7A is specified, the scan speed changing process of FIG. 8 is started. This process corresponds to "Yes" determined in step S4 of FIG. In this manner, the user's operation can be facilitated by using the user's enlargement processing (or reduction processing) as a trigger for changing the scanning speed.

Then, the scan speed change processing unit 112 sets the highest peak in the entire mass spectrum M to an ion intensity ratio (Intensity Ratio) of 100%, as shown in FIGS. 9A to 9C.

Also, as described above, the scan speed is not changed in the following cases.
(A1) When there is only a single peak within the expanded range 500, the scan speed change processing unit 112 does not change the scan speed.
(A2) After enlargement, if the height of peaks other than the maximum peak is 50% or less of the maximum peak, the half width cannot be obtained, so the scan speed change processing unit 112 does not change the scan speed.
The above (A1) and (A2) correspond to the case where condition #1 and condition #2 are not satisfied in step S602 of FIG.

Further, as described above, a plurality of pre-registered scan velocities are held in the scan velocity pattern 121 for each change m/z range 122 .
In this embodiment, as an example, scan speeds of 100 Da/s, 500 Da/s, and 1000 Da/s are held in the scan speed pattern 121 .
Next, the scan speed change processing unit 112 selects the scan speeds held in the scan speed pattern 121 one by one, and performs measurement (provisional measurement) of the measurement target once at the selected scan speed. This processing corresponds to steps S611 to S621 in FIG.

After that, the scan speed change processing unit 112 acquires the ion intensity ratio at the point where the valley between the peaks is the deepest in the measurement results at each scan speed. This process is the process of step S631 in FIG.
The ion intensity ratio at the point where the valley between peaks is the deepest is the ion intensity ratio when the highest peak point is taken as 100%.

FIG. 9A is a diagram showing provisional measurement results when the scan speed is 100 Da/s. FIG. 9B is a diagram showing provisional measurement results when the scan speed is 500 Da/s. FIG. 9C is a diagram showing provisional measurement results when the scan speed is 1000 Da/s.
As shown in FIG. 9A, at 100 Da/s, the ion intensity ratio at the point where the valley between the peaks in the mass spectrum M11 is the deepest is assumed to be 42%. Also, as shown in FIG. 9B, at 500 Da/s, the ion intensity ratio at the point where the valley between the peaks in the mass spectrum M12 is the deepest is assumed to be 25%. Further, as shown in FIG. 9C, at 1000 Da/s, the ion intensity ratio at the point where the valley between the peaks in the mass spectrum M13 is deepest is assumed to be 27%.

Then, the scan speed change processing unit 112 stores each scan speed and the corresponding ion intensity ratio as data in the storage unit 120 . In the example shown in FIGS. 9A to 9C, “100 Da/s: 42%”, “500 Da/s: 25%”, and “1000 Da/s: 27%” are stored in storage unit 120 .

After that, the scan speed change processing unit 112 compares each ion intensity ratio (S631 in FIG. 5) and selects the scan speed with the smallest ion intensity ratio. This determines an appropriate scan speed (S632 in FIG. 5).
Then, the scan speed change processing unit 112 sets the read scan speed as an appropriate scan speed for the change m/z range 122 in the control unit 210 of the mass spectrometer 200 (S633 in FIG. 5). Specifically, the scan speed change processing unit 112 sets the high frequency voltage value corresponding to the determined scan speed in the control unit 210 .
After that, the control unit 210 of the mass spectrometer 200 performs measurement at the set scan speed. As a result of this measurement, a mass spectrum M2 shown in FIG. 7B is obtained.

In the examples shown in FIGS. 9A to 9C, the valley is deepest at 500 Da/s. Therefore, in the example shown in FIGS. 9A to 9C, 500 Da/s (FIG. 9), which is the scan speed with the deepest valley between peaks, is determined as an appropriate scan speed.

Thus, in the first embodiment, the scan speed at which the valley in the mass spectrum M becomes the deepest is determined as the appropriate scan speed. The deepest trough means that each peak in the mass spectrum M becomes clear, and good mass resolution is obtained.

According to the first embodiment, a pointing device such as a mouse can be used to easily set the m/z range and appropriate scanning speed using the GUI. As a result, the m/z range to be measured can be changed and measurement can be performed at a scan speed corresponding to the m/z range without having knowledge of software explanations or mass spectrometry. As a result, even a user who has no knowledge of mass spectrometry or who does not know the position of the text box on the GUI screen can always keep the mass resolving power in an appropriate state.

That is, according to the first embodiment, a user who does not have knowledge of mass spectrometry can intuitively operate without knowledge of technical terms such as m / z values, and the mass resolution of the mass spectrum M is in an appropriate state. can be measured by Also, the mass resolution can be maintained in an appropriate state without the user being conscious of it.

Further, according to the first embodiment, with respect to the isotopic components displayed in the mass spectrum M, it is expected that the identification accuracy of the components (especially isotopes) will be improved due to the improved mass resolution.

Also, in the mass spectrometer 200, it is necessary to measure a sample with a known m/z value in advance to calibrate the mass of the mass spectrometer 200. Mass calibration is to calibrate the m/z value deviation based on the detected ion intensity. In general, the mass spectrometer 200 is calibrated by presetting the relationship between the m/z value and the high-frequency voltage corresponding to the m/z value. As a result, it is possible to maintain the accuracy of the ion trap that retains the ions of the component to be detected inside the mass spectrometer 200 and the control that ejects the ions of the specific component.

However, the relationship between the m/z value and the high-frequency voltage corresponding to the m/z value is susceptible to changes in temperature and humidity. Furthermore, since temperature and humidity change with time, the relationship between the m/z value and the high-frequency voltage corresponding to the m/z value changes with the lapse of time. A change in such a relationship is referred to as an m/z value shift.

When the m/z value deviates, the detected ions are observed with an m/z value that deviates from the true value, and the m/z value is determined to be different from the m/z value of the component to be measured. end up In this case, in general, the user visually determines the deviation of the m/z value, or mass calibration is performed by automatic detection.

According to the first embodiment, even if the mass spectrum M is scaled as described above, good mass resolution can be obtained. Therefore, the identification accuracy of the components used for mass calibration is improved, and the user can easily determine the necessity of mass calibration.
Further, according to the present embodiment, while monitoring the mass spectrum M, it is possible to select a component of the reagent used for mass calibration in the mass spectrometer 200 in consideration of the characteristics of each mass spectrometer 200 .

In addition to the temperature and humidity, problems of the mass spectrometer 200 itself also exist as factors for the deviation of the m/z value. For example, there is one that accompanies a change in scan speed.
The faster the scanning speed, the more qualitatively the components included in the measurement can be seen. In addition, the component to be measured can be quantitatively measured at a lower scanning speed. However, in mass spectrometry, if the scan speed is changed from low to high or from high to low, the m/z value will deviate, so it is necessary to correct the relationship between the m/z value and the high-frequency voltage each time.

In the first embodiment, an appropriate scanning speed is set for scaling of the mass spectrum M by the method described above. Therefore, it is not necessary to perform mass calibration accompanying changes in scan speed.

Also, updating the m/z range measured in the MS ¹ analysis in MS/MS and changing the scan speed are generally not performed. By the way, in ^US Pat.

On the other hand, by applying the method shown in the first embodiment to the measurement result during MS ¹ analysis, the scan speed change processing unit 112 scales the mass spectrum M during MS ¹ analysis m / z range The scan speed can be changed to correspond to (change m/z range 122). This allows measurements with appropriate scan rates in MS ¹ analysis to obtain good mass resolution. As a result, a mass spectrum M having good mass resolution can be obtained at the stage of MS ¹ , so that it is possible to prevent components to be measured in MS ¹ from being lost. Therefore, the accuracy of the entire MS/MS can be improved.

In addition, due to the good mass resolution, when the user confirms the deviation of the m / z value in SIM and SRM with the mass spectrum M, not only the target components of SIM and SRM but also the m The /z value isotope can be confirmed by the user. Accordingly, the user can also confirm the deviation of the m/z value of the components (isotopes) other than the target components of SIM and SRM. In other words, according to the first embodiment, as described above, by setting the scanning speed appropriate for scaling of the mass spectrum M in the control unit 219, good mass resolution can be obtained. Thereby, the user can confirm the ion intensity of multiple masses in the mass spectrum M2 displayed on the display unit 102 . Therefore, in SIM and SRM, the user evaluates not only the m/z value deviation of the components used in SIM and SRM, but also the m/z value deviation of components other than the components to be measured and components containing isotopes. , it is possible to assist the user in judging whether mass calibration is appropriate or not.

A common method for improving mass resolution is to manually adjust the RF voltage (ie, scan speed) to adjust the peak width. However, if the peak width is cut too much, the sensitivity may decrease.
On the other hand, in this embodiment, the scan speed change processing unit 112 determines an appropriate scan speed based on the scaled mass spectrum M. FIG. At this time, the scanning speed is determined based on the depth of the valley in the mass spectrum M. Therefore, it is possible to prevent a decrease in sensitivity due to excessive reduction of the peak width.

Also, in the first embodiment, as shown in FIG. 7A, an enlarged range 500 (or a reduced range) of the mass spectrum M1 is specified by dragging with a mouse. By doing so, even a user who does not have knowledge of operations related to mass spectrometry can easily enlarge or reduce the mass spectrum M1 and change the scan speed.

<Second embodiment>
A second embodiment of the present invention will now be described with reference to FIGS. 10A and 10B. Reference will be made to FIGS. 1 to 3 as appropriate.
In the first embodiment, a PC (Personal Computer) is assumed as the computing device 100, but there is a problem that the operation of the PC is not easy. The purpose of the second embodiment is to improve the ease of use as compared with the first embodiment.

In the second embodiment, a portable terminal such as a tablet terminal or a smart phone is used as the computing device 100 shown in FIG. Then, in the second embodiment, a process of enlarging the mass spectrum M (see FIGS. 7A and 7B) by a pinch-out operation on the touch panel will be described.

10A and 10B are diagrams showing specific processing of the enlargement/reduction processing (step S4 in FIG. 5) in the second embodiment. FIG. 10A shows an example of the mass spectrum M21 before enlarging, and FIG. 10B shows an example of the mass spectrum M21 after enlarging.
First, the user presses arbitrary two points on the touch panel screen indicated by

reference numerals

601 and 602 in the mass spectrum M21 shown in FIG. 10A. Arithmetic device 100 (portable terminal) uses the position information of the pressed finger of the user as a starting point. Next, the user slides the pressed finger on the screen of the display unit 101 to

positions

611 and 612 and releases the finger. The computing device 100 (portable terminal) uses this as the end point. Thereby, the expansion range 600 is set.

At this time, the computing device 100 (portable terminal) stores information on the m/z values of the

reference numerals

602 and 602 in the storage unit 120 . Further, the computing device 100 (portable terminal) stores the amounts of change of the

reference numerals

601 and 601 and the

reference numerals

602 and 612 with respect to the m/z axis. Arithmetic device 100 (portable terminal) then adds the amount of change to the position information of

reference numerals

601 and 602 . The computing device 100 (portable terminal) takes this as a new m/z range (changed m/z range 122 (see FIG. 3)).

As a result, the mass spectrum M22 shown in FIG. 10B, which is an enlarged part of the mass spectrum M21 shown in FIG. 10A, is displayed on the display unit 101. Note that the mass spectrum M22 shown in FIG. 10B shows the result of measurement performed at the determined appropriate scan speed, and therefore has a shape different from that of the mass spectrum M21.

The scan speed change processing unit 112 stores the m/z range obtained by such operation in the storage unit 120 as a new measurement range of the mass spectrum M (changed m/z range 122). The scan speed change processing unit 112 then acquires the changed m/z range 122 stored in the storage unit 120 .

Then, the scan speed change processing unit 112 determines an appropriate scan speed from the scan speeds saved in the scan speed pattern 121 based on the acquired information on the changed m/z range 122 . Since the process of determining an appropriate scanning speed is the same as that of the first embodiment, the description is omitted here.

Furthermore, the scan speed change processing unit 112 determines a high frequency voltage corresponding to the determined scan speed. The scan speed change processing unit 112 sets the determined high frequency voltage in the control unit 210 . Mass spectrometer 200 begins measurements at the changed m/z range 122 and the determined scan rate.

In the second embodiment, a tablet terminal, a smartphone, or the like is used as the computing device 100, and enlargement or reduction processing is performed by finger gestures. Thereby, 2nd Embodiment can improve a handiness rather than 1st Embodiment.

In this embodiment, in tandem mass spectrometry using a triple quadrupole or an ion trap, precursor ions are selected, the ions are subjected to collision-induced dissociation, and then product ions are detected in the second stage of mass spectrometry MS/MS. can be used in It can also be used in MS ⁿ analysis in which the mass spectrometry process is repeated multiple times (three or more times).

The present invention is not limited to the above-described embodiments, and includes various modifications. For example, the above-described embodiments have been described in detail in order to explain the present invention in an easy-to-understand manner, and are not necessarily limited to those having all the configurations described. Also, part of the configuration of one embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of one embodiment. Moreover, it is possible to add, delete, or replace part of the configuration of each embodiment with another configuration.

Also, the above configurations, functions,

units

110, 111 to 113, storage unit 120, and the like may be realized by hardware, for example, by designing a part or all of them using an integrated circuit. Further, as shown in FIG. 4, each configuration, function, etc. described above may be realized by software by a processor such as the CPU 132 interpreting and executing a program for realizing each function. Information such as programs, tables, files, etc. that realize each function is stored in the HD, and is stored in the memory 131, a recording device such as an SSD, an IC (Integrated Circuit) card, an SD (Secure Digital) card, It can be stored in a recording medium such as a DVD (Digital Versatile Disc).
Further, in each embodiment, control lines and information lines are those considered necessary for explanation, and not all control lines and information lines are necessarily shown on the product. In fact, it can be considered that almost all configurations are interconnected.

100 computing device (control device)
101 display unit 110 processing unit 111 acquisition unit (mass spectrum acquisition unit)
112 scan speed change processing unit (m/z range acquisition unit, setting unit)
113 display processing unit 120 storage unit 121 scan speed pattern 122 change m/z range 200 mass spectrometer 210 control unit 300 sample supply device 400 scan

speed setting screen

500, 600 expansion range M, M1, M2, M11 to M13, M21, M22 mass spectrum Z mass spectrometry system S3 mass spectrum acquisition (mass spectrum acquisition step)
S5 Storage of changed m/z range (m/z range acquisition step)
S6 scan speed change processing unit (scan speed change processing step)

Claims

A computing device in which a plurality of scan speeds are stored in advance as scan speed patterns in a storage unit,
a mass spectrum acquisition step of acquiring a first mass spectrum that is the result of measurement by the mass spectrometer;
an m/z range obtaining step of obtaining an m/z range of the expanded range or the reduced range when the user designates the expanded range or the reduced range of the first mass spectrum displayed on the display unit;
sequentially selecting the scan speeds stored in the scan speed pattern, causing the mass spectrometer to perform provisional measurement of the m/z range of the expansion range or contraction range at the selected scan speed; a scan speed change processing step of determining the scan speed in the m/z range of the expansion range or the contraction range based on the second mass spectrum obtained as a result of the measurement;
A method for assisting mass spectrometry, characterized by performing
In the scan speed change processing step,
signal intensity of the deepest point in the valley between peaks relative to the point with the highest signal intensity for each of the second mass spectra obtained in the provisional measurements at each of the scan velocities selected from the scan velocity pattern; 2. The mass spectrometry assisting method according to claim 1, wherein the scan speed for the second mass spectrum having the smallest ratio of is determined as the scan speed.
2. The mass spectrometry support method according to claim 1, wherein said scan speed change processing step is performed based on designation of an expansion range or a contraction range of said first mass spectrum.
2. The method of supporting mass spectrometry according to claim 1, wherein the specification of the expansion range or contraction range is performed by a user operating a mouse.
The first mass spectrum is displayed on the touch panel screen,
2. The mass spectrometry support method according to claim 1, wherein the designation of the expansion range or the reduction range is performed by a user's operation of a touch panel.
a storage unit in which a plurality of scan speeds are stored in advance as scan speed patterns;
a mass spectrum acquisition unit that acquires a first mass spectrum that is the result of measurement by a mass spectrometer;
an m/z range acquisition unit that acquires the m/z range of the expansion range or contraction range when the user specifies the expansion range or contraction range of the first mass spectrum displayed on the display unit;
sequentially selecting the scan speeds stored in the scan speed pattern, causing the mass spectrometer to perform provisional measurement of the m/z range of the expansion range or contraction range at the selected scan speed; a scan speed change processing unit that determines the scan speed in the m/z range of the expansion range or the contraction range based on the second mass spectrum obtained as a result of the measurement;
A mass spectrometry support device characterized by having:
a mass spectrometer;
a control device that controls the mass spectrometer;
has
The control device is
a storage unit in which a plurality of scan speeds are stored in advance as scan speed patterns;
a mass spectrum acquisition unit that acquires a first mass spectrum that is the result of measurement by a mass spectrometer;
an m/z range acquisition unit that acquires the m/z range of the expansion range or contraction range when the user specifies the expansion range or contraction range of the first mass spectrum displayed on the display unit;
sequentially selecting the scan speeds stored in the scan speed pattern, causing the mass spectrometer to perform provisional measurement of the m/z range of the expansion range or contraction range at the selected scan speed; a scan speed change processing unit that determines the scan speed in the m/z range of the expansion range or the contraction range based on the second mass spectrum obtained as a result of the measurement;
a setting unit that sets the determined scan speed to the mass spectrometer;
A mass spectrometry support system comprising: