Mass spectrometry system

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

Technical Field

[0001] The present invention relates to a mass spectrometry system.

Background Art

[0002] In a time-of-flight mass spectrometer (hereinafter referred to as "TOFMS"), ions derived from a measurement target substance generated by an ion source using a matrix-assisted laser desorption / ionization (MALDI) method or the like are given a certain kinetic energy and accelerated, and then made to fly in a flight space of a predetermined length. Since the flight speed of each ion introduced into the flight space is higher as the mass-to-charge ratio (strictly, m / z) is smaller, various ions emitted from the ion source simultaneously pass through the flight space in ascending order of m / z and reach the detector. That is, various ions are separated temporally according to m / z. Since the flight time of each ion derived from the measurement target substance has a predetermined relationship with m / z, if the flight time is measured for each ion species, the m / z of each ion species can be calculated from this measured value.

[0003] In order to achieve a high mass resolution in TOFMS, ions having the same m / z need to reach the detector as simultaneously as possible, that is, it is necessary to have high time focusing. However, generally, in the MALDI method, although the space where ions are generated is very small, the spread (variation) of the initial velocities of the generated ions is relatively large. Such variation in the initial velocities of ions is a major factor in the decrease in time focusing in TOFMS, leading to a decrease in mass resolution. Therefore, in order to improve the time focusing in TOFMS, a method generally called the delayed extraction method has been widely used conventionally (see, for example, Non-Patent Document 1).

[0004] In a typical delayed extraction method, an electric field is not formed near the ion generation site for a certain period after ion generation by laser irradiation, allowing the ions to fly freely and broaden their spatial distribution. Then, after a predetermined delay time has elapsed from the time of ion generation, a pulsed voltage is applied to an extraction electrode placed in front of the sample plate, creating an accelerating electric field with a downward potential gradient from the sample plate towards the extraction electrode. At the time of pulsed voltage application, i.e., after a certain delay time has elapsed from the time of ion generation, ions with lower initial velocities are closer to the sample plate (i.e., further from the extraction electrode), so ions with lower initial velocities are given greater kinetic energy by the high accelerating voltage. This reduces the effect of variations in initial velocities at the time of ion generation, improving the time convergence, or mass resolution, in TOFMS. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Koichi Tanaka, et al., "Fundamentals of Delayed Extraction Method," Journal of the Japan Society for Mass Spectrometry, 2009, Vol. 57, No. 1, pp. 31-36. [Overview of the Initiative] [Problems that the invention aims to solve]

[0006] Incidentally, in recent years, a simple method for identifying microorganisms has been developed using a TOFMS equipped with an ion source that performs sample ionization by MALDI as described above (hereinafter referred to as MALDI-TOFMS). This method identifies microorganisms based on the mass spectral pattern obtained using the test microorganism, and since analytical results can be obtained in a short time, it enables simple and rapid identification of microorganisms. In this method, first, a solution containing components extracted from the test microorganism or a suspension of the test microorganism is analyzed using MALDI-TOFMS. Then, the obtained mass spectrum is compared with the mass spectrum of a known microorganism to identify the microbial species or strain of the test microorganism.

[0007] In the delayed extraction method, the mass resolution is highest at a specific m / z value determined by parameters such as the delay time, and decreases as the value moves away from this specific m / z. Therefore, it is important to appropriately set the parameters related to delayed extraction (hereinafter referred to as delayed extraction parameters) according to the m / z of interest.

[0008] However, in microbial analysis using MALDI-TOFMS as described above, there is a problem in that it is difficult to appropriately set the delayed extraction parameter because the peaks of interest, such as ribosomal proteins useful for microbial identification, are detected over a wide m / z range.

[0009] This type of problem is common not only to proteins derived from microorganisms, but also to the analysis of samples that produce peaks across a wide m / z range, such as lipids derived from microorganisms, other lipids, or synthetic polymers.

[0010] The present invention has been made in view of the above points, and its objective is to enable easy determination of appropriate delay extraction parameters when analyzing a sample that produces peaks over a wide m / z range using a time-of-flight mass spectrometer. [Means for solving the problem]

[0011] The mass spectrometry system according to the present invention, which was developed to solve the above problems, is a mass spectrometry system comprising 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 and introduces them into the flight space, and then separates and detects the ions according to their m / z values ​​within that flight space. The control computer, A model sample analysis data storage unit stores, in association with the results of multiple mass analyses performed on a model sample while varying the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method, and the value of the delayed extraction parameter applied to each of the multiple mass analyses. The mass spectrometer to be used for analysis includes an input receiving unit that receives input of the type of sample or the m / z range of interest, An average value calculation unit calculates the average value of the mass resolution, ionic strength, or S / N ratio in the m / z range of interest, or in a predetermined m / z range according to the type of the sample being examined, for each of the results of the multiple mass analyses stored in the model sample analysis data storage unit. A parameter determination unit determines the value of the delayed extraction parameter stored in the model sample analysis data storage unit, corresponding to the value with the highest average value among the results of the multiple mass analyses, as the optimal value for the analysis of the test sample using the mass spectrometer. It is equipped with these features. [Effects of the Invention]

[0012] According to the mass spectrometry system of the present invention described above, when analyzing a sample that produces peaks over a wide m / z range using a time-of-flight mass spectrometer, it becomes possible to easily determine appropriate delay extraction parameters. [Brief explanation of the drawing]

[0013] [Figure 1] A diagram showing the main components of a mass spectrometry system according to one embodiment of the present invention. [Figure 2] A first schematic diagram illustrating the ion extraction operation by the delayed extraction method. [Figure 3] A second schematic diagram illustrating the ion extraction operation using the delayed extraction method. [Figure 4] A flowchart showing the procedure for determining the optimal delay time in the above embodiment. [Figure 5]A diagram showing an example of a display screen for presenting a heat map and an optimal delay time to the user. [Figure 6] A flowchart showing another example of a procedure for determining an optimal delay time.

Mode for Carrying Out the Invention

[0014] Hereinafter, embodiments for carrying out the present invention will be described with reference to the drawings. FIG. 1 is a configuration diagram of a main part of a mass spectrometry system according to an embodiment of the present invention. The mass spectrometry system according to the present embodiment includes a time-of-flight mass spectrometer (hereinafter referred to as TOFMS10) and a control / processing unit 30.

[0015] TOFMS10 includes an ion source for ionizing a sample by the MALDI method, and along an ion optical axis C substantially orthogonal to a sample plate 15 holding a sample 16, an extraction electrode 21, a base electrode 22, a flight space 25 formed in a flight tube 24, and a detector 26 are arranged. A sample 16 formed by mixing a measurement object (for example, microbial cells) and a matrix is held on the sample plate 15. The laser light emitted from the laser light source 11 is irradiated onto the surface of the sample 16 through the condenser lens 12 and the mirror 13.

[0016] The extraction voltage application unit 23 applies a predetermined DC voltage 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, and a voltage is applied to the sample plate 15 through the stage 14.

[0017] The detector 26 is, for example, a photomultiplier tube, which detects ions that are sequentially separated in time according to m / z in the process of passing through the flight space 25 and outputs a detection signal corresponding to the ion amount. This detection signal is converted into digital data by an analog-to-digital converter (ADC) 27 and input to a data processing unit 31 provided in the control / processing unit 30.

[0018] The data processing unit 31 creates a time-of-flight spectrum showing the relationship between time of flight and ion intensity based on the detected signal, and creates a mass spectrum by converting the time of flight to m / z based on pre-determined calibration information.

[0019] The control / processing unit 30 is composed of a computer such as a personal computer, and is connected to an input unit 40 equipped with a keyboard and mouse, and a display unit 50 (corresponding to the display device in this invention) consisting of a liquid crystal display, etc. In addition to the data processing unit 31 described above, the control / processing unit 30 includes 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 ​​as functional blocks. These functional blocks are all basically functional means that are realized in software by executing a dedicated program pre-installed on the computer that constitutes the control / processing unit 30 on the computer's CPU. The dedicated program does not necessarily have to be a standalone program; for example, it may be a function incorporated into a program for controlling the TOFMS 10, and its form is not particularly limited.

[0020] The control / processing unit 30 is configured to access the storage unit 60, which consists of a large-capacity storage device such as an HDD (Hard Disk Drive) or 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 or directly connected to the computer that constitutes the control / processing unit 30, or it may be a storage device located on another computer system accessible from the computer via the Internet or the like, i.e., a storage device in cloud computing.

[0021] In this embodiment, the TOFMS10 performs ion extraction using a delayed extraction method when ionizing the sample 16. The basic operation of the TOFMS10 in the delayed extraction method will be described below.

[0022] First, at a predetermined point in time before the sample 16 is irradiated with laser light for ionization, the extraction voltage application unit 23 applies the same voltage V to the stage 14 and the extraction electrode 21 under the control of the analysis control unit 32. E Apply a voltage V to the base electrode 22. E Base voltage V is significantly smaller in absolute value than B Apply the voltage. Generally, the base electrode 22 is grounded, so here V B Let = 0. As a result, the potential distribution on the ion optical axis C will be as shown in Figure 2. That is, there is no potential gradient in the extraction region between the sample plate 15 and the extraction electrode 21, and an electric field with a potential gradient that slopes downward from the extraction electrode 21 toward the base electrode 22 is formed in the acceleration region between the extraction electrode 21 and the base electrode 22. Note that Figure 2 shows the potential distribution when extracting positive ions, and when extracting negative ions, the positive and negative signs of the potential will be reversed from that shown in the figure.

[0023] Subsequently, the analysis control unit 32 controls the laser light source 11 to emit pulsed laser light and briefly irradiate the sample 16. At this time, as described above, there is no potential gradient in the extraction region between the sample plate 15 and the extraction electrode 21, so the ions generated from the sample 16 by the laser light irradiation are not accelerated. Therefore, ions with larger initial energy at the time of ion generation move further away from the sample 16 (to the right in Figure 2). As a result, after a certain amount of time has elapsed since ion generation, regardless of the ion's m / z, ions with larger initial energy are located closer to the extraction electrode 21.

[0024] After a predetermined delay time (usually several tens to several hundred nanoseconds) has elapsed since the irradiation of the laser light, the analysis control unit 32 calculates the absolute value of the voltage applied from the extraction voltage application unit 23 to the sample plate 15, V E From V SThe potential is increased to this extent. As a result, as shown in Figure 3, an electric field with a downward-sloping potential gradient is formed in the extraction region from the sample plate 15 toward the extraction electrode 21. This electric field accelerates all the ions that were present in the extraction region immediately before it. At this time, ions closer to the sample plate 15, that is, ions with lower initial energy, receive acceleration due to a higher (i.e., larger absolute value) potential, and therefore the kinetic energy given to the ions is greater. Consequently, even for the same type of ions (i.e., ions with the same m / z), those with lower initial energy at the time of generation are sent into the flight space 25 at a greater speed, and the ions introduced later into the flight space 25 gradually catch up with the preceding ions of the same type with relatively higher initial energy during their flight, and finally reach the detector 26 almost simultaneously. In this way, the effect of variations in the initial energy of ions of the same type is eliminated, and high time convergence can be achieved.

[0025] However, in this delayed extraction method, the mass resolution is highest at a specific m / z value determined by the parameters related to delayed extraction (e.g., the delay time mentioned above), and the mass resolution decreases as the value moves away from this specific m / z. Therefore, in the delayed extraction method described above, it is important to appropriately set the parameters related to delayed extraction (hereinafter referred to as delayed extraction parameters) according to the m / z of interest.

[0026] The following describes the procedure for setting the delay extraction parameter, which is a characteristic operation of the mass spectrometry system according to this embodiment, with reference to the flowchart in Figure 4. The following explanation will use the case where the delay time is set as the delay extraction parameter as an example, but other delay extraction parameters (for example, the voltage V mentioned above) may be used in addition to or instead of the delay time. E Or voltage V S You may also set the value of (or both).

[0027] The model sample analysis data storage unit 61 stores, in advance, data of multiple mass spectra obtained by mass spectrometry of multiple types of model samples with varying delay times in the delayed extraction method, as model sample analysis data. These multiple types of model samples can be, for example, model samples for microbial protein analysis and model samples for microbial lipid analysis. Here, a model sample for microbial protein analysis is a sample obtained by mixing cells or extracts of a predetermined microorganism (e.g., Escherichia coli) with a matrix suitable for protein mass spectrometry, and a model sample for microbial lipid analysis is a sample obtained by mixing cells or extracts of a predetermined microorganism with a matrix suitable for lipid mass spectrometry. It is desirable that the model sample analysis data is obtained 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 TOFMS 10 manufacturer and stored in the model sample analysis data storage unit 61, or it may be obtained by the user by actually mass spectrometry of the model sample using the TOFMS 10 and stored in the model sample analysis data storage unit 61.

[0028] [Step 101: Input of the type of test sample and the m / z range of interest is accepted] First, when the user (analyst) performs a predetermined operation on the input unit 40, a predetermined setting screen is displayed on the screen of the display unit 50 under the control of the display control unit 36. The setting screen is configured to accept input of the type of sample to be analyzed using the mass spectrometer (i.e., the test sample) and the m / z range to be of interest in the analysis of the test sample (hereinafter referred to as the "m / z range of interest"). In other words, in this step, the display control unit 36 ​​functions as the input receiving unit 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" can be displayed on the setting screen, and the user can select one of them. In this case, if the test sample consists of cells of a predetermined microorganism or an extract thereof mixed with a matrix suitable for protein mass spectrometry, the user selects "microbial protein" as the type of test sample. On the other hand, if the test sample consists of cells of a predetermined microorganism or an extract thereof mixed with a matrix suitable for lipid mass spectrometry, the user selects "microbial lipid" as the type of test sample. The input format for the aforementioned m / z range of interest can be, for example, by having the user input the lower and upper limits of the m / z range of interest numerically on the settings screen.

[0029] Generally, when performing mass spectrometry on microorganisms using MALDI-TOFMS, the target range for analysis is m / z 2000 to 20000, where peaks of proteins derived from microorganisms are frequently detected. Of these, ribosomal protein peaks are known to appear in the m / z 9000 to 14000 range. Therefore, if the type of sample is "microbial protein," the user should input a range of m / z 9000 to 14000 as the target m / z range. Similarly, in mass spectrometry using MALDI-TOFMS, peaks of lipids derived from microorganisms are generally detected in the m / z 500 to 2000 range. Therefore, if the type of sample is "microbial lipid," the user should input a range of m / z 500 to 2000 as the target m / z range. If the type of sample is a synthetic polymer, the user should input a range of m / z 200 to 3000 as the target m / z range.

[0030] [Step 102: Read out model sample analysis data corresponding to the type of test sample] When the user inputs the type of sample to be tested and the m / z range of interest via the input unit 40, the mean value calculation unit 33 then reads model sample analysis data corresponding to the type of sample to be tested from the model sample analysis data storage unit 61. For example, if "microbial protein" is input as the type of sample to be tested in step 101, then in this step, multiple mass spectra related to the "model sample for microbial protein analysis" (i.e., the results of multiple mass analyses performed on the model sample, each with a different delay time applied) are read out.

[0031] [Step 103: Calculate the average value of the mass resolution] Furthermore, the average value calculation unit 33 extracts peaks included in the target m / z range for each of the multiple mass spectra, determines the mass resolution of each peak, and calculates its average value. [Step 104: Determining the Optimal Delay Time] Next, the parameter determination unit 34 determines the optimal delay time for the analysis of the test sample (hereinafter referred to as the optimal delay time) by assigning it to the delay time stored in the model sample analysis data storage unit 61, which corresponds to the mass spectrum with the highest average value of mass resolution in the m / z range (i.e., the delay time that was applied when the mass spectrum was acquired).

[0032] [Step 105: Creating a Heatmap] Furthermore, the image generation unit 35 creates a heatmap representing the 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 heatmap may have, for example, multiple cells identified by a combination of the m / z of the peaks included in each of the multiple mass spectra and the delay time when each mass spectrum was acquired, and the level of mass resolution in each of the combinations may be represented by the intensity of the color assigned to each cell (see Figure 5). However, the heatmap in this embodiment is not limited to the above, as long as it is an image that visually represents the distribution of mass resolution in a two-dimensional region where one of the vertical or horizontal axes is m / z and the other is delay time. For example, the level of mass resolution may be represented by differences in hue, lightness, or saturation of the color assigned to each cell, differences in the pattern assigned to each cell, or a combination thereof.

[0033] Note that steps 104 and 105 above may be performed in reverse order.

[0034] [Step 106: Displaying Optimal Delay Time and Heatmap] Next, 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 displays the optimal delay time and the heat map, and is configured to accept changes to the optimal delay time by the user. In other words, in this step, the display control unit 36 ​​functions as a parameter change acceptance unit in the present invention.

[0035] An example of the display screen is shown in Figure 5. The user checks the heat map displayed in the heat map display area 71 and the optimal delay time displayed in the optimal delay time display area 72 on the display screen, and if they determine that there are no particular problems, they press the OK button 73 via the input unit 40. As a result, the value of the optimal delay time is set as the delay time value to be applied to the mass analysis of the test sample.

[0036] On the other hand, if the user checks the heatmap and the delay time value and determines that a change in the delay time is necessary, the user presses the change button 74 via the input unit 40. This makes, for example, the optimal delay time display field 72 editable, and when the user changes the delay time value in that field to an appropriate value and presses the OK button 73, the changed delay time value is set as the delay time applied to the mass analysis of the test sample.

[0037] As a result, the delay time value applied to the mass spectrometry of the test sample is set to an appropriate value according to the type of test sample and the m / z range of interest. Subsequently, the user places the test sample in the ion source of the TOFMS 10 and instructs the analysis control unit 32 to start the mass spectrometry via the input unit 40, thereby executing the mass spectrometry with the applied delay time.

[0038] Furthermore, even when mass spectrometry is performed on the same object to be measured (e.g., a suspension of microorganisms) using the same delay time, the mass resolution at each m / z will differ depending on the sample preparation method (e.g., the type of matrix used for preparation). Therefore, it is desirable to apply the same preparation method to the test sample as to the model sample corresponding to the test sample. Accordingly, the mass spectrometry system according to this embodiment may display the preparation method of the test sample in addition to displaying the optimal delay time as described above. Specifically, for example, for multiple model samples whose model sample analysis data is stored in the model sample analysis data storage unit 61, information such as the type of matrix applied to the preparation of each model sample, the mixing ratio of the object to be measured (e.g., a suspension of microbial cells or an extract of microbial cells) and the matrix, or the mixing procedure of the object to be measured and the matrix is ​​stored in the storage unit 60 in advance. Then, at a predetermined point in time after the user inputs the type of test sample in step 101, the display control unit 36 ​​reads the preparation method stored for the model sample corresponding to the type of test sample from the storage unit 60 and displays it on the screen of the display unit 50. The user prepares the test sample according to the preparation method displayed on the display unit 50. The preparation method may be displayed simultaneously with the optimal delay time in step 106, or it may be displayed at a different time from the optimal delay time (for example, immediately before or after step 106, or immediately after step 101).

[0039] In the example described above, data for multiple model samples is stored in the model sample analysis data storage unit 61 in advance, and the optimal delay time is determined by reading out the model sample analysis data according to the type of sample being tested. However, the method is not limited to this, and model sample analysis data for a single model sample corresponding to the type of sample being tested may be obtained, and the optimal delay time for the sample being tested may be determined based on this data.

[0040] An example of a procedure for determining the optimal delay time in such cases will be explained with reference to the flowchart in Figure 6.

[0041] [Step 201: Accept input for the target m / z range] First, when the user (analyst) performs a predetermined operation on the input unit 40, a predetermined setting screen is displayed on the screen of the display unit 50 under the control of the display control unit 36. The setting screen is configured to accept input of the m / z range of interest for mass spectrometry of the sample under test, and the user inputs the m / z range of interest to the setting screen via the input unit 40.

[0042] [Step 202: Mass spectrometry of model sample] Subsequently, the user places the sample plate 15 holding the model sample into the ion source of the MALDI-TOFMS 10. At this time, the model sample is made by mixing the same type of object to be measured as the test sample (e.g., microorganisms) with the same matrix used to prepare the test sample. Then, the user instructs the analysis control unit 32 to start mass spectrometry via the input unit 40, and multiple mass spectrometry analyses are performed on the model sample with varying delay times. As a result, the data processing unit 31 generates multiple 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 unit 61.

[0043] [Step 203: Calculate the average value of the mass resolution] Next, the average value calculation unit 33 reads out the multiple mass spectra generated in step 202, extracts the peaks included in the target m / z range for each of them, determines the mass resolution of each peak, and calculates its average value. [Step 204: Determining the Optimal Delay Time] Next, the parameter determination unit 34 determines the delay time that was applied when the mass spectrum with the highest average value was obtained as the optimal delay time for the analysis of the test sample.

[0044] The subsequent steps, namely steps 205 and 206, are the same as steps 105 and 106 described above, so their explanation will be omitted here.

[0045] Although the embodiments for carrying out the present invention have been described above with specific examples, the present invention is not limited to the above embodiments, and modifications are permitted as appropriate within the scope of the spirit of the 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 determined as the optimal delay time in step 104 (or step 204). Alternatively, in step 103 (or step 203), the average value of the peak height (i.e., ion detection intensity) or S / N ratio (i.e., signal-to-noise ratio) included in the m / z range of interest may be calculated, and the delay time corresponding to the mass spectrum with the highest value may be determined as the optimal delay time in step 104 (or step 204).

[0046] Furthermore, 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 model sample analysis data. However, the system is not limited to this, and a list is also stored which contains the m / z values ​​of the peaks included in the mass spectrum and the mass resolution (or ionic intensity or S / N ratio) of the peaks, associated with the delay time applied when the mass spectrum was acquired. In this case, the list corresponds to the model sample analysis data in the present invention.

[0047] 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, a heat map showing the distribution of ionic intensity or signal-to-noise ratio may be generated and displayed. Alternatively, instead of a heat map, an image (i.e., a contour map) representing the high and low levels of mass resolution (or ionic intensity or signal-to-noise ratio) with contour lines may be created and displayed. Also, the heat map or contour map does not necessarily have to be displayed on the display unit 50. In that case, step 105 (or step 205) is omitted, and in step 106 (or step 206), only information regarding the optimal delay time is displayed.

[0048] Furthermore, the mass spectrometry system according to this embodiment may not display the optimal delay time as described above, and the optimal delay time determined in step 104 (or step 204) may be automatically set as the delay time to be applied to the subsequent analysis of the test sample. In that case, steps 105 and 106 (or steps 205 and 206) described above may be omitted.

[0049] Furthermore, although the above embodiment uses a TOFMS equipped with a MALDI ion source as an example, the ion source is not limited to this. Any ion source that uses an ionization method and is used as an ion source for TOFMS, which generates ions from the sample in a short time and extracts and accelerates those ions using an electric field to send them into the flight space, can be used. Examples of such ion sources include ion sources that do not utilize a matrix, such as laser desorption ionization (LDI), secondary ion mass spectrometry (SIMS), desorption electrospray ionization (DESI), and plasma desorption ionization (PDI). [Pattern] It will be obvious to those skilled in the art that the exemplary embodiments described above are specific examples of the following embodiments.

[0050] (Section 1) A mass spectrometry system according to one aspect of the present invention is: A mass spectrometry system comprising 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 and introduces them into the flight space, and then separates and detects the ions according to their m / z values ​​within that flight space. The control computer, A model sample analysis data storage unit stores, in association with the results of multiple mass analyses performed on a model sample while varying the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method, and the value of the delayed extraction parameter applied to each of the multiple mass analyses. The mass spectrometer to be used for analysis includes an input receiving unit that receives input of the type of sample or the m / z range of interest, An average value calculation unit calculates the average value of the mass resolution, ionic strength, or S / N ratio in the m / z range of interest, or in a predetermined m / z range according to the type of the sample being examined, for each of the results of the multiple mass analyses stored in the model sample analysis data storage unit. A parameter determination unit determines the value of the delayed extraction parameter stored in the model sample analysis data storage unit, corresponding to the value with the highest average value among the results of the multiple mass analyses, as the optimal value for the analysis of the test sample using the mass spectrometer. It is equipped with.

[0051] According to the mass spectrometry system described in paragraph 1, the optimal value of the delayed extraction parameter for the mass analysis of the sample is automatically determined based on the type of sample to be tested or the m / z range of interest for the sample to be tested, as entered by the user via the input reception unit. This makes it easy to determine an appropriate delayed extraction parameter for samples that produce peaks over a wide m / z range (for example, those where the difference between the upper and lower limits is 1000 m / z or more).

[0052] (Paragraph 2) The mass spectrometry system relating to Paragraph 2 is, in the mass spectrometry system relating to Paragraph 1, The aforementioned model sample analysis data storage unit stores the results of the multiple mass spectrometry operations for each of the multiple types of model samples. The average value calculation unit calculates the average value of the results of multiple mass analyses for the model sample corresponding to the type of test sample input by the input reception unit, from among the multiple types of model samples.

[0053] According to the mass spectrometry system described in paragraph 2, the mass spectrometry results for a model sample corresponding to the type of test sample entered by the user are automatically selected from among the mass spectrometry results for multiple types of model samples, and appropriate delayed extraction parameters are determined based on these mass spectrometry results. Therefore, even when analyzing various types of test samples with the mass spectrometer, appropriate delayed extraction parameters for each test sample can be easily determined.

[0054] (Paragraph 3) The mass spectrometry system relating to Paragraph 3 is, in the mass spectrometry system relating to Paragraph 1 or Paragraph 2, The control computer further, Display device and An image generation unit generates an image representing the distribution of mass resolution, ionic intensity, or signal-to-noise ratio in a two-dimensional region where one of the vertical or horizontal axes is m / z and the other is the delayed extraction parameter, based on the results of the multiple mass spectrometry tests performed on the model sample. A display control unit that displays the image on the display device together with the optimal value determined by the parameter determination unit, A parameter change receiving unit that accepts changes to the aforementioned optimal value, It is equipped with these features.

[0055] According to the mass spectrometry system described in paragraph 3, the user can visually grasp the level of mass resolution, ionic intensity, or signal-to-noise ratio for each combination of m / z and delayed extraction parameter based on the image displayed on the display device. This allows the user to determine whether the value of the delayed extraction parameter determined by the parameter determination unit is appropriate, and furthermore, the value can be changed via the parameter change reception unit as needed.

[0056] (Article 4) The mass spectrometry system relating to Article 4 is, in the mass spectrometry system relating to Article 2 or Article 3, The control computer further, Display device and A display control unit that controls the display device, A preparation method storage unit that stores the preparation method for each of the aforementioned multiple types of model samples, Equipped with, The display control unit causes the display device to display the preparation method stored in the preparation method storage unit for a model sample from among the multiple types of model samples that corresponds to the type of test sample input by the input reception unit.

[0057] According to the mass spectrometry system described in paragraph 4, the user can easily find out how the model sample corresponding to the test sample—that is, the model sample used to determine the optimal delay extraction parameters for the mass analysis of the test sample—was prepared. Furthermore, by preparing the test sample using the same preparation method as the model sample, the user can prevent changes in mass resolution and other parameters due to differences in preparation methods.

[0058] (Article 5) The mass spectrometry method relating to Article 5 is: A time-of-flight mass spectrometer is used to perform mass spectrometry, in which ions generated from a sample are accelerated by a delayed extraction method and introduced into the flight space, and the ions are separated and detected in the flight space according to their m / z ratio. Multiple mass analyses were performed on the model sample while varying the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method. For each of the results of the aforementioned multiple mass analyses, the average value of the mass resolution, ionic intensity, or signal-to-noise ratio in the m / z range of interest for the sample to be analyzed with the time-of-flight mass spectrometer is calculated. The value of the delayed extraction parameter applied when the highest average value was obtained from the multiple mass spectrometry results is determined as the optimal value for the mass spectrometry of the test sample. The aforementioned optimal value is applied, and the mass analysis of the sample is performed using the time-of-flight mass spectrometer.

[0059] According to the mass spectrometry method described in paragraph 5, even if the test sample produces peaks over a wide m / z range, mass spectrometry can be easily performed on the test sample using appropriate delayed extraction parameters. [Explanation of symbols]

[0060] 10…TOFMS 11… Laser light source 15…Sample Plate 16… Sample 21...Drawer electrode 22…Base electrode 23...Drawer voltage application section 24... Flight Tube 25…Airspace 26…Detector 30…Control / Processing Unit 31...Data Processing Unit 32…Analysis and Control Section 33...Average value calculation section 34...Parameter determination unit 35…Image generation unit 36…Display Control Unit 40...Input section 50...Display section 60...Storage section 61...Model sample analysis data storage unit 71... Heatmap display area 72... Optimal delay time display field

Claims

1. A mass spectrometry system comprising a mass spectrometer and a control computer capable of communicating with the mass spectrometer, The aforementioned mass spectrometer accelerates ions generated from a sample by a delayed extraction method and introduces them into the flight space, and then separates and detects the ions according to their m / z values ​​within that flight space. The control computer, A model sample analysis data storage unit stores, in association with the results of multiple mass analyses performed on a model sample while varying the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method, and the value of the delayed extraction parameter applied to each of the multiple mass analyses. The mass spectrometer to be used for analysis includes an input receiving unit that receives input of the type of sample or the m / z range of interest, An average value calculation unit calculates the average value of the mass resolution, ionic intensity, or S / N ratio of each peak in the m / z range of interest, or in a predetermined m / z range according to the type of the sample being examined, for each of the results of the multiple mass analyses stored in the model sample analysis data storage unit. A parameter determination unit determines the value of the delayed extraction parameter stored in the model sample analysis data storage unit, corresponding to the value with the highest average value among the results of the multiple mass analyses, as the optimal value for the analysis of the test sample using the mass spectrometer. A mass spectrometry system equipped with the following features.

2. The aforementioned model sample analysis data storage unit stores the results of the multiple mass spectrometry operations for each of the multiple types of model samples. The average value calculation unit calculates the average value of the results of the multiple mass spectrometry tests for the model sample corresponding to the type of test sample input by the input receiving unit, among the multiple types of model samples. The mass spectrometry system according to claim 1.

3. The control computer further, Display device and An image generation unit generates an image representing the distribution of mass resolution, ionic intensity, or S / N ratio in a two-dimensional region where one of the vertical or horizontal axes is m / z and the other is the delayed extraction parameter, based on the results of the multiple mass spectrometry tests performed on the model sample. A display control unit that displays the image on the display device together with the optimal value determined by the parameter determination unit, A parameter change receiving unit that accepts changes to the aforementioned optimal value, A mass spectrometry system according to claim 1 or 2, comprising:

4. The control computer further, Display device and A display control unit that controls the display device, A preparation method storage unit that stores the preparation method for each of the aforementioned multiple types of model samples, Equipped with, The display control unit causes the display device to display the preparation method stored in the preparation method storage unit for a model sample from among the multiple types of model samples that corresponds to the type of test sample input by the input reception unit. The mass spectrometry system according to claim 2.

5. A time-of-flight mass spectrometer is used to perform mass spectrometry, in which ions generated from a sample are accelerated by a delayed extraction method and introduced into flight space, and the ions are separated and detected in the flight space according to their m / z ratio. Multiple mass analyses were performed on the model sample while varying the value of the delayed extraction parameter, which is a parameter related to the delayed extraction method. For each of the results of the aforementioned multiple mass analyses, the average value of the mass resolution, ionic intensity, or signal-to-noise ratio of each peak in the m / z range of interest for the sample to be analyzed with the time-of-flight mass spectrometer is calculated. The value of the delayed extraction parameter applied when the highest average value was obtained from the multiple mass spectrometry results is determined as the optimal value for the mass spectrometry of the test sample. A mass spectrometry method comprising applying the aforementioned optimal value and performing mass spectrometry of the sample to be examined using the time-of-flight mass spectrometer.

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