JP2024022199A - mass spectrometry system - Google Patents

Abstract

To allow a proper delay extracting parameter to be easily decided when analyzing a sample which generates a peak in a wide m/z range by a time-of-flight mass spectrometer.SOLUTION: A mass spectrometry system comprises: a time-of-flight mass spectrometer 10 which performs extraction of ions by means of the delay extraction method; and a control computer. The control computer comprises: a model sample analysis data storage unit 61 which stores results of plural times of mass spectrometry performed by changing the delay time in the delay extraction method to the model sample; an input reception unit 36 which receives an input of a target m/z range in an inspection object sample; an average value calculation unit 33 which calculates an average value of the mass resolution in the target m/z range for each of the results of the plural times of mass spectrometry; and a parameter decision unit 34 which decides the delay time corresponding to the mass spectrometry result whose average value becomes highest as a value optimum for analysis of the inspection object sample.SELECTED DRAWING: Figure 1

Description

The present invention relates to a mass spectrometry system.

In a Time-Of-Flight Mass Spectrometer (hereinafter referred to as "TOFMS"), ions are generated using an ion source using Matrix Assisted Laser Desorption/Ionization (MALDI) method. Ions derived from the substance to be measured are given a certain amount of kinetic energy, accelerated, and made to fly in a flight space of a predetermined length. The flight speed of each ion introduced into the flight space increases as the mass-to-charge ratio (strictly speaking, m/z) decreases, so various ions emitted from the ion source at the same time pass through the flight space in order of decreasing m/z and are detected. reach the vessel. That is, various ions are temporally separated according to m/z. The flight time of each ion derived from the substance to be measured has a predetermined relationship with m/z, so if the flight time is measured for each ion species, the m/z of each ion species can be calculated from this measured value. .

In order to achieve high mass resolution in TOFMS, ions with the same m/z must arrive at the detector as simultaneously as possible, that is, it is necessary to have high time convergence. However, in general, in the MALDI method, although the space in which ions are generated is very small, the initial velocity spread (dispersion) of the generated ions is relatively large. Such variations in the initial velocity of ions are a major cause of a decrease in time convergence in TOFMS, leading to a decrease in mass resolution. Therefore, in order to improve the time convergence in TOFMS, a technique commonly called the delayed extraction method has been widely used (for example, see Non-Patent Document 1).

In the general delayed extraction method, an electric field is not formed near the ion generation site for a certain period of time after ion generation by laser beam irradiation, and the ions are allowed to fly freely to widen their spatial distribution. Then, after a predetermined delay time has elapsed from the time of ion generation, a pulse voltage is applied to the extraction electrode placed in front of the sample plate to form an accelerating electric field with a downward potential gradient from the sample plate toward the extraction electrode. At the time when a pulse voltage is applied, that is, when a certain delay time has elapsed from the time when ions are generated, ions with a lower initial velocity are located closer to the sample plate (i.e., farther from the extraction electrode). , a large amount of kinetic energy is imparted due to the high accelerating voltage. This reduces the influence of variations in initial velocity at the time of ion generation, and improves time convergence, that is, mass resolution in TOFMS.

Koichi Tanaka, and 2 others, “Basics of delayed extraction method”, Journal of the Mass Spectrometry Society of Japan, 2009, Vol. 57, No. 1, pp. 31-36

Incidentally, in recent years, a simple method for identifying microorganisms has been developed using TOFMS (hereinafter referred to as MALDI-TOFMS) equipped with an ion source that ionizes a sample by MALDI as described above. This is a method for identifying microorganisms based on mass spectrum patterns obtained using test microorganisms, and because analysis results can be obtained in a short time, it is possible to identify microorganisms easily and quickly. . In this method, first, a solution containing components extracted from the test microorganism or a suspension of the test microorganism is analyzed by MALDI-TOFMS. Then, by comparing the obtained mass spectrum with the mass spectra of known microorganisms, the microorganism species or strain of the test microorganism is identified.

In the delayed extraction method, the mass resolution is highest at a specific m/z value determined by parameters such as delay time, and the mass resolution decreases as the distance from the specific m/z increases. Therefore, it is important to appropriately set parameters related to delayed withdrawal (hereinafter referred to as delayed withdrawal parameters) according to the m/z of interest.

However, in microbial analysis using MALDI-TOFMS as described above, noteworthy peaks, such as peaks of ribosomal proteins useful for microbial identification, are detected over a wide m/z range, resulting in delays. There is a problem in that it is difficult to appropriately set withdrawal parameters.

Such problems are common in the analysis of samples that produce peaks in a wide m/z range, such as not only proteins derived from microorganisms but also lipids derived from microorganisms, other lipids, or synthetic polymers.

The present invention has been made in view of the above points, and its purpose is to provide an appropriate method for analyzing samples with peaks in a wide m/z range using a time-of-flight mass spectrometer. The objective is to enable easy determination of delayed withdrawal parameters.

A mass spectrometry system according to the present invention made to solve the above problems is a mass spectrometry system including a mass spectrometer and a control computer capable of communicating with the mass spectrometer,
The mass spectrometer accelerates ions generated from a sample using a delayed extraction method, introduces the ions into a flight space, and separates and detects ions according to m/z within the flight space,
The control computer
The results of multiple mass spectrometry analyzes performed on a model sample while changing the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method, and the delayed extraction applied to each of the multiple mass spectrometry analyses. a model sample analysis data storage unit that stores parameter values in association with each other;
an input reception unit that receives input of the type of the test sample or the m/z range of interest for the test sample to be analyzed using the mass spectrometer;
For each of the results of the plurality of mass spectrometry measurements stored in the model sample analysis data storage unit, the m/z range of interest or the m/z range predetermined according to the type of the test sample an average value calculation unit that calculates an average value of any of the mass resolution, ion intensity, or S/N ratio;
Using the mass spectrometer, the value of the delayed extraction parameter stored in the model sample analysis data storage unit is associated with the one with the highest average value among the results of the plurality of mass spectrometry analyses. a parameter determination unit that determines the optimum value for the analysis of the test sample;
It is equipped with the following.

According to the mass spectrometry system according to the present invention, when analyzing a sample that has peaks in a wide m/z range using a time-of-flight mass spectrometer, it is possible to easily determine an appropriate delay extraction parameter. Become.

FIG. 1 is a configuration diagram of main parts of a mass spectrometry system according to an embodiment of the present invention. The first schematic diagram for explaining the ion extraction operation by the delayed extraction method. FIG. 3 is a second schematic diagram for explaining the ion extraction operation using the delayed extraction method. 5 is a flowchart showing a procedure for determining an optimal delay time in the embodiment. The figure which shows an example of the display screen for presenting a heat map and optimal delay time to a user. 7 is a flowchart showing another example of the procedure for determining the optimal delay time.

DESCRIPTION OF EMBODIMENTS Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings. FIG. 1 is a configuration diagram of main parts of a mass spectrometry system according to an embodiment of the present invention. The mass spectrometry system according to this embodiment includes a time-of-flight mass spectrometer (hereinafter referred to as TOFMS 10) and a control/processing section 30.

The TOFMS 10 is equipped with an ion source that ionizes a sample using the MALDI method, and the extraction electrode 21, the base electrode 22, and the inside of the flight tube 24 are arranged along an ion optical axis C that is substantially perpendicular to the sample plate 15 that holds the sample 16. A flight space 25 and a detector 26 are arranged. A sample 16 consisting of a mixture of an object to be measured (for example, microbial cells) and a matrix is held on the sample plate 15 . Laser light emitted from the laser light source 11 passes through the condensing lens 12 and the reflecting mirror 13 and is irradiated onto the surface of the sample 16 .

The extraction voltage applying section 23 applies predetermined DC voltages to the sample plate 15, the extraction electrode 21, and the base electrode 22, respectively. The sample plate 15 is made of a conductive material such as metal or conductive glass, and is held on the stage 14 so that a voltage is applied to the sample plate 15 via the stage 14.

The detector 26 is, for example, a photomultiplier tube, and detects ions that are temporally separated according to m/z and arrive sequentially in the process of passing through the flight space 25, and outputs a detection signal according to the amount of ions. . This detection signal is converted into digital data by an analog-to-digital converter (ADC) 27 and input to a data processing section 31 provided in a control/processing section 30.

The data processing unit 31 creates a time-of-flight spectrum indicating the relationship between flight time and ion intensity based on the detection signal, and creates a mass spectrum by converting the flight time into m/z based on calibration information obtained in advance. do.

The control/processing section 30 is composed of a computer such as a personal computer, and the computer includes an input section 40 equipped with a keyboard, a mouse, etc., and a display section 50 (corresponding to a display device in the present invention) consisting of a liquid crystal display, etc. ) are connected. The control/processing unit 30 includes, as functional blocks, an analysis control unit 32, an average value calculation unit 33, a parameter determination unit 34, an image generation unit 35, and a display control unit 36 in addition to the data processing unit 31 described above. There is. These functional blocks are basically functional means realized in software by executing a dedicated program pre-installed in the computer constituting the control/processing section 30 on the CPU of the computer. . The dedicated program does not necessarily have to be a standalone program, and may be a function incorporated into a part of a program for controlling the TOFMS 10, and its form is not particularly limited.

The control/processing section 30 is configured to be able to access a storage section 60 consisting of a mass storage device such as a HDD (Hard Disk Drive) or an SSD (Solid State Drive). The storage unit 60 is provided with a model sample analysis data storage unit 61 . The storage unit 60 may be a storage device built into the computer constituting the control/processing unit 30 or directly connected to the computer, or may be a storage device that is accessible from the computer via the Internet or the like. In other words, it may exist on a computer system, such as a storage device in cloud computing.

In the TOFMS 10 in this embodiment, when ionizing the sample 16, ion extraction is performed using a delayed extraction method. The basic operation of the TOFMS 10 in the delayed extraction method will be described below.

First, at a predetermined time point before the sample 16 is irradiated with laser light for ionization, the extraction voltage application section 23 applies the same voltage V to the stage 14 and the extraction electrode 21 under the control of the analysis control section 32. _E is applied to the base electrode 22, and a base voltage _VB whose absolute value is sufficiently smaller than the voltage _VE is applied to the base electrode 22. Since the base electrode 22 is generally grounded, V _B =0 here. As a result, the potential distribution on the ion optical axis C becomes as shown in FIG. That is, there is no potential gradient in the extraction region between the sample plate 15 and the extraction electrode 21, and there is a downward slope from the extraction electrode 21 toward the base electrode 22 in the acceleration region between the extraction electrode 21 and the base electrode 22. An electric field with a potential gradient is formed. Note that FIG. 2 shows the potential distribution when positive ions are extracted, and when negative ions are extracted, the polarity of the potential is opposite to that in the figure.

Thereafter, the analysis control unit 32 controls the laser light source 11 to emit pulsed laser light to irradiate the sample 16 for a short time. At this time, since there is no potential gradient in the extraction region between the sample plate 15 and the extraction electrode 21 as described above, the ions generated from the sample 16 by the laser beam irradiation are not accelerated. Therefore, when ions are generated, ions with larger initial energy move further away from the sample 16 (move to the right in FIG. 2). As a result, when a certain period of time has elapsed since ion generation, ions with larger initial energy are located closer to the extraction electrode 21, regardless of the m/z of the ions.

When a predetermined delay time (usually about several tens to hundreds of nanoseconds) has elapsed since the laser beam irradiation, the analysis control unit 32 changes the absolute value of the voltage applied from the extraction voltage application unit 23 to the sample plate 15 from V _E to Increase to _VS. As a result, as shown in FIG. 3, an electric field having a downwardly inclined potential gradient from the sample plate 15 toward the extraction electrode 21 is formed in the extraction region. Due to this electric field, various ions that were present in the extraction region immediately before the electric field are accelerated all at once. At this time, the closer the ion is to the sample plate 15, that is, the smaller the initial energy, the faster the ion is accelerated by the higher potential (ie, the larger the absolute value), and therefore the greater the kinetic energy given to the ion. Therefore, even if the ions are of the same type (that is, ions with the same m/z), the smaller the initial energy at the time of ion generation, the faster the ions will be sent into the flight space 25, and the later they will be introduced into the flight space 25. During their flight, the ions gradually catch up with the preceding ions of the same type whose initial energy is relatively large, and finally reach the detector 26 almost simultaneously. In this way, the influence of variations in initial energy among ions of the same type is eliminated, and high time convergence can be achieved.

However, in such delayed extraction methods, the mass resolution is highest at a specific m/z value determined by parameters related to delayed extraction (e.g., the above-mentioned delay time, etc.), and the mass resolution decreases as the distance from the specific m/z increases. do. Therefore, in the delayed withdrawal method as described above, it is important to appropriately set parameters related to delayed withdrawal (hereinafter referred to as delayed withdrawal parameters) according to the m/z of interest.

The procedure for setting delayed extraction parameters, which is a characteristic operation of the mass spectrometry system according to this embodiment, will be described below with reference to the flowchart of FIG. 4. The following explanation will be given using an example in which a delay time is set as a delay extraction parameter, but in addition to or in place of the delay time, other delay extraction parameters (for example, the value of the _{voltage V} (both) settings may be made.

Note that the model sample analysis data storage unit 61 stores data of a plurality of mass spectra obtained by performing mass spectrometry on a plurality of types of model samples while varying the delay time in the delayed extraction method. , is stored as model sample analysis data. The plurality of types of model samples can be, for example, a model sample for microbial protein analysis and a model sample for microbial lipid analysis. Here, the model sample for microbial protein analysis is a sample obtained by mixing cells of a predetermined microorganism (for example, Escherichia coli) or an extract thereof with a matrix suitable for protein mass spectrometry, and is a model sample for microbial lipid analysis. The sample is a sample prepared by mixing cells of a given microorganism or an extract thereof with a matrix suitable for lipid mass spectrometry. It is desirable that the model sample analysis data be acquired using the TOFMS 10 in this embodiment or a mass spectrometer having a similar configuration. Such model sample analysis data may be prepared by the manufacturer of the TOFMS 10 and stored in the model sample analysis data storage unit 61, or may be prepared by the user by actually performing mass spectrometry on a model sample using the TOFMS 10. It may be acquired and stored in the model sample analysis data storage section 61.

[Step 101: Accept input of test sample type and m/z range of interest]
First, when a user (person in charge of analysis) performs a predetermined operation on the input section 40, a predetermined setting screen is displayed on the screen of the display section 50 under the control of the display control section 36. The setting screen displays the type of sample (i.e., test sample) that will be analyzed using the mass spectrometer, and the m/z range of interest in analyzing the test sample (hereinafter referred to as the m/z range of interest). ) is configured to accept input. That is, in this step, the display control section 36 functions as an input reception section in the present invention. As an input format for the type of test sample, for example, multiple options such as "microbial protein" and "microbial lipid" are displayed on the setting screen and the user is asked to select one of them. Can be done. In this case, if the test sample is made by mixing cells of a predetermined microorganism or an extract thereof with a matrix suitable for protein mass spectrometry, the user selects "microbial protein" as the type of test sample. ”. On the other hand, when the test sample is a mixture of cells of a predetermined microorganism or an extract thereof with a matrix suitable for lipid mass spectrometry, the user selects "microbial lipid" as the type of test sample. select. As an input format for the m/z range of interest, for example, the user may input numerical values on the lower limit and upper limit of the m/z range of interest on the setting screen.

Generally, when microorganisms are subjected to mass spectrometry using MALDI-TOFMS, the m/z range of 2000 to 20000, where peaks of proteins derived from microorganisms are frequently detected, is the target of analysis. Among these, it is known that the peak of ribosomal proteins appears in the m/z range of 9000 to 14000. Therefore, when the type of test sample is "microbial protein", the user inputs, for example, a range of m/z 9000 to 14000 as the m/z range of interest. Furthermore, it is known that in mass spectrometry using MALDI-TOFMS, peaks of lipids derived from microorganisms are generally detected in the m/z range of 500 to 2000. Therefore, when the type of test sample is "microbial lipid," the user inputs, for example, a range of m/z 500 to 2000 as the m/z range of interest. Note that when the type of test sample is a synthetic polymer, the user inputs, for example, a range of m/z 200 to 3000 as the m/z range of interest.

[Step 102: Read out model sample analysis data corresponding to the type of test sample]
When the user inputs the type of test sample and the m/z range of interest via the input unit 40, the average value calculation unit 33 converts the model sample analysis data according to the type of test sample into a model sample. Read from the analysis data storage section 61. For example, if "microbial protein" is input as the type of test sample in step 101, in this step, a plurality of mass spectra related to the above-mentioned "model sample for microbial protein analysis" (i.e., each mass spectrum for the model sample is The results of multiple mass spectrometry analyzes performed using different delay times are read out.

[Step 103: Calculate the average value of mass resolution]
Furthermore, the average value calculation unit 33 extracts peaks included in the m/z range of interest for each of the plurality of mass spectra, determines the mass resolution of each peak, and calculates the average value.
[Step 104: Determination of optimal delay time]
Next, the parameter determination section 34 determines the delay time (i.e., the mass spectrum The delay time that was applied when the spectrum was acquired) is determined as the optimal delay time (hereinafter referred to as the optimal delay time) for the analysis of the test sample.

[Step 105: Creating a heat map]
Further, the image generation unit 35 creates a heat map represented by a distribution of mass resolution at each delay time and each m/z based on the mass resolution of each peak calculated in step 103. The heat map has, for example, a plurality of cells specified by a combination of m/z of a peak included in each of the plurality of mass spectra and a delay time when each mass spectrum is acquired, and the combination An image can be created in which the level of mass resolution in each cell is expressed by the shade of color assigned to each cell (see FIG. 5). However, the heat map in this embodiment is an image that visually represents the distribution of mass resolution in a two-dimensional region where one of the vertical axis or the horizontal axis is m/z and the other is the delay time. For example, the level of mass resolution may be expressed by differences in hue, brightness, or saturation of the color applied to each cell, differences in patterns applied to each cell, or a combination thereof. You can.

Note that the above steps 104 and 105 may be performed in the reverse order.

[Step 106: Display of optimal delay time and heat map]
Subsequently, the display control unit 36 causes the display unit 50 to display a display screen showing the optimal delay time value determined in step 104 and the heat map image created in step 105. This display screen is configured to display the optimum delay time and the heat map, and to accept changes to the optimum delay time by the user. That is, in this step, the display control section 36 functions as a parameter change reception section in the present invention.

An example of the display screen is shown in FIG. The user checks the heat map displayed in the heat map display field 71 on the display screen and the optimal delay time displayed in the optimal delay time display field 72, and if the user determines that there is no particular problem, input The OK button 73 is pressed via the section 40. Thereby, the value of the optimum delay time is set as the value of the delay time applied to mass spectrometry of the test sample.

On the other hand, if the user checks the heat map and the value of the delay time and determines that the delay time needs to be changed, the user presses the change button 74 via the input unit 40. As a result, for example, the optimal delay time display field 72 becomes editable, and when the user changes the delay time value in the field to an appropriate value and presses the OK button 73, the changed delay time value is changed. is set as a delay time applied to mass spectrometry of the test sample.

As a result of the above, the value of the delay time applied to the mass spectrometry of the test sample is set to an appropriate value according to the type of the test sample and the m/z range of interest. Thereafter, the user sets the test sample in the ion source of the TOFMS 10 and instructs the analysis control unit 32 to start mass spectrometry via the input unit 40, thereby performing mass spectrometry using the delay time. Ru.

Note that even when mass spectrometry is performed using the same delay time for the same measurement target (for example, a suspension of microorganisms), each m The mass resolution at /z is different. Therefore, in preparing the test sample, it is desirable to apply the same preparation method as the model sample corresponding to the test sample. Therefore, in addition to displaying the optimum delay time as described above, the mass spectrometry system according to the present embodiment may display the preparation method of the test sample. Specifically, for example, regarding a plurality of model samples whose model sample analysis data is stored in the model sample analysis data storage unit 61, the type of matrix applied to the preparation of each model sample, the type of measurement target (for example, microorganisms) Information such as the mixing ratio of the cell suspension (cell suspension or microbial cell extract) and the matrix, or the mixing procedure of the measurement object and the matrix is stored in advance in the storage unit 60. Then, at a predetermined time point after the user inputs the type of test sample in step 101, the display control unit 36 displays the preparation method stored in the storage unit 60 for the model sample corresponding to the type of test sample. The data is read out from the screen and displayed on the screen of the display unit 50. The user prepares the test sample according to the preparation method displayed on the display section 50. Note that in the preparation method, the optimum delay time may be displayed at the same time as the optimum delay time in step 106, or may be displayed at a timing different from the optimum delay time (for example, immediately before or after step 106, or immediately after step 101, etc.) You may also do so.

In the above example, the model sample analysis data storage unit 61 stores data regarding a plurality of model samples in advance, and the model sample analysis data corresponding to the type of test sample is read out to determine the optimal delay time. However, the present invention is not limited to this, but it is also possible to acquire model sample analysis data for a single model sample corresponding to the type of test sample and determine the optimal delay time for the test sample based on this. Good too.

An example of the procedure for determining the optimal delay time in such a case will be explained with reference to the flowchart of FIG. 6.

[Step 201: Accept input of m/z range of interest]
First, when a user (person in charge of analysis) performs a predetermined operation on the input section 40, a predetermined setting screen is displayed on the screen of the display section 50 under the control of the display control section 36. The setting screen is configured to be able to accept an input of the m/z range of interest in mass spectrometry of a test sample, and the user inputs the m/z range of interest to the setting screen via the input unit 40.

[Step 202: Mass spectrometry of model sample]
Thereafter, the user sets the sample plate 15 holding the model sample in the ion source of the MALDI-TOFMS 10. At this time, the model sample is a mixture of the same type of measurement object (for example, microorganisms) as the test sample and the same matrix used for preparing the test sample. Thereafter, when the user instructs the analysis control section 32 to start mass spectrometry via the input section 40, mass spectrometry is performed on the model sample a plurality of times while changing the delay time. As a result, the data processing section 31 generates a plurality of mass spectra for a predetermined m/z range that includes at least the m/z range of interest, and stores them in the model sample analysis data storage section 61.

[Step 203: Calculate the average value of mass resolution]
Next, the average value calculation unit 33 reads out the plurality of mass spectra generated in step 202, extracts peaks included in the m/z range of interest from each of them, and calculates the mass resolution of each peak. , calculate the average value.
[Step 204: Determination of optimal delay time]
Next, the parameter determining unit 34 determines the delay time that was applied when the mass spectrum with the highest average value was acquired as the optimal delay time for analyzing the test sample.

The subsequent steps, ie, Steps 205 and 206, are the same as Steps 105 and 106 described above, so the description thereof will be omitted here.

Although the embodiments for carrying out the present invention have been described above with reference to specific examples, the present invention is not limited to the above-mentioned embodiments, and modifications may be made as appropriate within the scope of the spirit of the present invention. For example, in the above example, in step 103 (or step 203), the average value of the mass resolution of the peaks included in the m/z range of interest is calculated, and the delay time corresponding to the mass spectrum with the highest value is calculated. , is determined as the optimum delay time in step 104 (or step 204), but instead of this, in step 103 (or step 203), the height of the peak included in the m/z range of interest (i.e., the ion The average value of the detection intensity) or SN ratio (i.e., signal-to-noise ratio) is calculated, and the delay time corresponding to the mass spectrum with the highest value is determined as the optimal delay time in step 104 (or step 204). It can also be used as a thing.

Further, in the above example, the mass spectrum obtained by mass spectrometry of the model sample is stored in the model sample analysis data storage unit 61 as the model sample analysis data, but the present invention is not limited to this. A list is stored in which the m/z of peaks included in the data and the mass resolution (or ion intensity or S/N ratio) of the peaks are associated with the value of the delay time applied when acquiring the mass spectrum. You can also do this. In this case, the list corresponds to model sample analysis data in the present invention.

Furthermore, in the above example, a heat map representing the distribution of mass resolution is created and displayed in steps 105 and 106 (or steps 205 and 206), but instead of this, the heat map representing the distribution of mass resolution is created and displayed. A heat map showing the distribution may be generated and displayed. Alternatively, instead of the heat map, an image (ie, a contour map) in which the heights of mass resolution (or ion intensity or SN ratio) are expressed by contour lines may be created and displayed. Furthermore, the heat map or contour map does not necessarily need to be displayed on the display unit 50. In that case, step 105 (or step 205) is omitted, and only information regarding the optimal delay time is displayed in step 106 (or step 206).

Furthermore, the mass spectrometry system according to the present embodiment does not display the optimal delay time as described above, and the optimal delay time determined in step 104 (or step 204) is applied to the subsequent analysis of the test sample. The delay time may be automatically set. In that case, steps 105 and 106 (or steps 205 and 206) described above are omitted.

Furthermore, in the above embodiment, a TOFMS equipped with a MALDI ion source is used as an ion source, but the ion source is not limited to this, and may be an ion source using an ionization method used as an ion source for TOFMS. Any ion source may be used as long as it is configured to generate ions from a sample in a short period of time, extract the ions using an electric field, accelerate them, and send them into the flight space. Examples of such ion sources include laser desorption ionization (LDI) that does not use a matrix, secondary ion mass spectrometry (SIMS), and desorption electrospray ionization (DESI). For example, an ion source using a plasma desorption ionization (PDI) method may be used.
[Mode]
It will be apparent to those skilled in the art that the exemplary embodiments described above are specific examples of the following aspects.

(Section 1) A mass spectrometry system according to one aspect of the present invention includes:
A mass spectrometry system including a mass spectrometer and a control computer capable of communicating with the mass spectrometer,
The mass spectrometer accelerates ions generated from a sample using a delayed extraction method, introduces the ions into a flight space, and separates and detects ions according to m/z within the flight space,
The control computer
The results of multiple mass spectrometry analyzes performed on a model sample while changing the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method, and the delayed extraction applied to each of the multiple mass spectrometry analyses. a model sample analysis data storage unit that stores parameter values in association with each other;
an input reception unit that receives input of the type of the test sample or the m/z range of interest for the test sample to be analyzed using the mass spectrometer;
For each of the results of the plurality of mass spectrometry measurements stored in the model sample analysis data storage unit, the m/z range of interest or the m/z range predetermined according to the type of the test sample an average value calculation unit that calculates the average value of any of the mass resolution, ion intensity, or S/N ratio;
Using the mass spectrometer, the value of the delayed extraction parameter stored in the model sample analysis data storage unit is associated with the one with the highest average value among the results of the plurality of mass spectrometry analyses. a parameter determination unit that determines the optimum value for the analysis of the test sample;
Equipped with.

According to the mass spectrometry system according to item 1, the test sample is automatically determined based on the type of test sample or the m/z range of interest for the test sample input by the user via the input reception unit. Since the optimal delayed extraction parameter value for mass spectrometry is determined, it is easy to determine the appropriate delayed extraction parameter for samples that produce peaks in a wide m/z range (for example, those with a difference between the upper and lower limits of m/z 1000 or more). will be able to decide.

(Section 2) The mass spectrometry system according to Section 2 is the mass spectrometry system according to Section 1,
The model sample analysis data storage unit stores the results of the plurality of mass spectrometry analyzes for each of the plurality of types of model samples,
The average value calculation unit calculates the average value of the results of the plurality of mass spectrometry measurements regarding the model sample corresponding to the type of test sample input by the input reception unit among the plurality of types of model samples. It is something to do.

According to the mass spectrometry system according to Section 2, the mass spectrometry results of the model sample corresponding to the type of test sample input by the user are automatically selected from the mass spectrometry results of multiple types of model samples. , appropriate delayed extraction parameters are determined based on the mass spectrometry results. Therefore, even when various types of test samples are analyzed by the mass spectrometer, it is possible to easily determine appropriate delay extraction parameters for each test sample.

(Paragraph 3) The mass spectrometry system according to Paragraph 3 is the mass spectrometry system according to Paragraph 1 or Paragraph 2,
The control computer further comprises:
a display device;
Based on the results of the plurality of mass spectrometry analyzes on the model sample, the mass resolution, ion intensity, or SN in a two-dimensional region where one of the vertical axis or the horizontal axis is m/z and the other is the delayed extraction parameter. an image generation unit that generates an image representing the ratio distribution;
a display control unit that causes the display device to display the image together with the optimal value determined by the parameter determination unit;
a parameter change reception unit that accepts a change in the optimal value;
It is equipped with the following.

According to the mass spectrometry system according to Item 3, the user can determine the level of mass resolution, ion intensity, or S/N ratio for each combination of m/z and delayed extraction parameter based on the image displayed on the display device. It can be grasped visually. This makes it possible for the user to judge whether the value of the delayed withdrawal parameter determined by the parameter determination section is appropriate, and further to change the value via the parameter change acceptance section as necessary. be able to.

(Section 4) The mass spectrometry system according to Section 4, in the mass spectrometry system according to Section 2 or 3,
The control computer further comprises:
a display device;
a display control unit that controls the display device;
a preparation method storage unit that stores preparation methods for each of the plurality of types of model samples;
Equipped with
The display control unit displays the preparation method stored in the preparation method storage unit for a model sample corresponding to the type of test sample input by the input receiving unit among the plurality of types of model samples. It is displayed on a display device.

According to the mass spectrometry system according to Section 4, the model sample corresponding to the test sample, that is, the model sample used when determining the optimal delay extraction parameters for mass spectrometry of the test sample, is The user can easily know whether the By having the user prepare the test sample using the same preparation method as the model sample, it is possible to prevent changes in mass resolution and the like due to differences in preparation methods.

(Section 5) The mass spectrometry method according to Section 5 is:
A mass spectrometry method using a time-of-flight mass spectrometer in which ions generated from a sample are accelerated by a delayed extraction method and then introduced into a flight space, where the ions are separated and detected according to m/z. And,
Performing mass spectrometry on the model sample multiple times while changing the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method,
For each of the results of the multiple mass spectrometry analyses, the average value of any one of the mass resolution, ion intensity, or SN ratio in the m/z range of interest for the test sample to be analyzed by the time-of-flight mass spectrometer. Calculate,
Determining the value of the delayed extraction parameter that was applied when the one with the highest average value was obtained among the results of the multiple mass spectrometry analyses, as the optimal value for mass spectrometry of the test sample. death,
The optimum value is applied to perform mass spectrometry of the test sample using the time-of-flight mass spectrometer.

According to the mass spectrometry method according to item 5, even if the test sample has a peak in a wide m/z range, mass spectrometry can be easily performed on the test sample using an appropriate delay extraction parameter. be able to.

10...TOFMS
11... Laser light source 15... Sample plate 16... Sample 21... Extracting electrode 22... Base electrode 23... Extracting voltage applying section 24... Flight tube 25... Flight space 26... Detector 30... Control/processing section 31... Data processing section 32... Analysis control section 33...Average value calculation section 34...Parameter determination section 35...Image generation section 36...Display control section 40...Input section 50...Display section 60...Storage section 61...Model sample analysis data storage section 71...Heat map display field 72...Optimum delay time display field

Claims (5)

A mass spectrometry system including a mass spectrometer and a control computer capable of communicating with the mass spectrometer,
The mass spectrometer accelerates ions generated from a sample using a delayed extraction method, introduces the ions into a flight space, and separates and detects ions according to m/z within the flight space,
The control computer
The results of multiple mass spectrometry analyzes performed on a model sample while changing the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method, and the delayed extraction applied to each of the multiple mass spectrometry analyses. a model sample analysis data storage unit that stores parameter values in association with each other;
an input reception unit that receives input of the type of the test sample or the m/z range of interest for the test sample to be analyzed using the mass spectrometer;
For each of the results of the plurality of mass spectrometry measurements stored in the model sample analysis data storage unit, the m/z range of interest or the m/z range predetermined according to the type of the test sample an average value calculation unit that calculates the average value of any one of the mass resolution, ion intensity, or S/N ratio;
Using the mass spectrometer, the value of the delayed extraction parameter stored in the model sample analysis data storage unit is associated with the one with the highest average value among the results of the plurality of mass spectrometry analyses. a parameter determination unit that determines the optimum value for the analysis of the test sample;
A mass spectrometry system equipped with The model sample analysis data storage unit stores the results of the plurality of mass spectrometry analyzes for each of the plurality of types of model samples,
The average value calculation unit calculates the average value of the results of the plurality of mass spectrometry measurements regarding the model sample corresponding to the type of test sample input by the input reception unit among the plurality of types of model samples. do,
The mass spectrometry system according to claim 1. The control computer further comprises:
a display device;
Based on the results of the plurality of mass spectrometry analyzes on the model sample, the mass resolution, ion intensity, or SN in a two-dimensional region where one of the vertical axis or the horizontal axis is m/z and the other is the delayed extraction parameter. an image generation unit that generates an image representing the ratio distribution;
a display control unit that causes the display device to display the image together with the optimal value determined by the parameter determination unit;
a parameter change reception unit that accepts a change in the optimal value;
The mass spectrometry system according to claim 1 or 2, comprising: The control computer further comprises:
a display device;
a display control unit that controls the display device;
a preparation method storage unit that stores preparation methods for each of the plurality of types of model samples;
Equipped with
The display control unit displays the preparation method stored in the preparation method storage unit for a model sample corresponding to the type of test sample input by the input receiving unit among the plurality of types of model samples. display on a display device,
The mass spectrometry system according to claim 2. A mass spectrometry method using a time-of-flight mass spectrometer in which ions generated from a sample are accelerated by a delayed extraction method and then introduced into a flight space, where the ions are separated and detected according to m/z. And,
Performing mass spectrometry on the model sample multiple times while changing the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method,
For each of the results of the multiple mass spectrometry analyses, the average value of any one of the mass resolution, ion intensity, or SN ratio in the m/z range of interest for the test sample to be analyzed by the time-of-flight mass spectrometer. Calculate,
Determining the value of the delayed extraction parameter that was applied when the one with the highest average value was obtained among the results of the multiple mass spectrometry analyses, as the optimal value for mass spectrometry of the test sample. death,
A mass spectrometry method, wherein the time-of-flight mass spectrometer performs mass spectrometry of the test sample by applying the optimal value.

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