Mass spectrometry data analysis method and imaging mass spectrometry apparatus

Abstract

An imaging mass spectrometry device according to an embodiment of the present invention comprises: a measurement unit (1) that obtains data by performing mass spectrometry for each of a plurality of micro-regions in a measurement region on a sample; an analysis region determination unit (21) that determines a plurality of analysis regions each including a plurality of the micro-regions obtained by dividing the measurement region or by following a user's designation for the inside of the measurement region; a spectrum calculation unit (22, 23) that obtains an individual integrated mass spectrum by averaging or adding up profile spectra based on data obtained by the measurement unit for a plurality of micro-regions included in each one of the plurality of analysis regions; a peak information integration unit (24, 25) that detects a peak of each of the plurality of individual integrated spectra, collects peak information including at least the m / z value of the detected peak in each of the plurality of analysis regions, collects the peak information of the plurality of analysis regions, and obtains integrated peak information by arranging peaks inferred to have substantially the same m / z value; and a display process unit (26) that generates a peak list or mass spectrum based on the integrated peak information, and displays the peak list or mass spectrum on a display unit.

Description

[Technical field]

[0001] The present invention relates to an imaging mass spectrometer and a method for analyzing data collected by an imaging mass spectrometer. [Background technology]

[0002] An imaging mass spectrometer is a device capable of visualizing the distribution of compounds on a sample such as a biological tissue slice. The imaging mass spectrometer disclosed in Patent Document 1 is equipped with an ion source using a matrix-assisted laser desorption / ionization (MALDI) method, and collects mass spectrum data over a predetermined mass-to-charge ratio range (strictly speaking, this is written as "m / z" in italics, but in this specification, it is conventionally referred to as "mass-to-charge ratio" or simply "m / z") for each micro-region obtained by finely dividing a two-dimensional measurement region on the sample.

[0003] Another method of imaging mass spectrometry is known in which a sample collection method called laser microdissection is used to cut out sample pieces from each micro-area within the measurement area, and liquid samples prepared from each sample piece are fed to a mass spectrometer to obtain mass spectrum data for each micro-area (see Patent Document 2). Here, devices using such sample collection methods are also included in the imaging mass spectrometer.

[0004] In any case, an imaging mass spectrometer can extract, for example, signal intensity values ​​at the m / z values ​​of ions derived from a specific compound from the mass spectrum data obtained for each micro-region on the sample, and create an image in which the signal intensity values ​​are arranged according to the two-dimensional position of each micro-region on the sample, thereby obtaining an image showing the distribution of the specific compound. Hereinafter, such an image is referred to as an MS (Mass Spectrometry) imaging image. In a typical imaging mass spectrometer, when the compound to be observed, i.e. the target compound, is determined, the user specifies the m / z value corresponding to that compound, and an MS imaging image at that m / z value is then created and displayed on the display screen.

[0005] On the other hand, if the target compound is not specified, the user selects an appropriate mass peak while viewing the acquired mass spectrum, and the imaging mass spectrometer then creates an MS imaging image corresponding to the m / z value of the selected mass peak and displays it on the display screen.

[0006] As described in Patent Document 1, in such cases, an average mass spectrum created by averaging multiple mass spectra obtained for all micro-regions in the measurement region, or an integrated mass spectrum created by simply integrating the multiple mass spectra, is often used as a mass spectrum for a user to select a mass peak. This is because it is generally believed that information about all compounds present in the measurement region is reflected in the average mass spectrum or integrated mass spectrum (since the average mass spectrum and the integrated mass spectrum are essentially the same, only the average mass spectrum will be mentioned in the following explanation, but the same applies to the integrated mass spectrum). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] JP 2011-191222 A [Patent Document 2] International Publication No. 2015 / 053039 Summary of the Invention [Problem to be solved by the invention]

[0008] However, the above-mentioned analysis method in the conventional imaging mass spectrometer has the following problems.

[0009] The above-mentioned average mass spectrum is obtained by averaging so-called profile spectra, which are created based on raw data obtained by mass spectrometry for each small region within the measurement region. The width of the mass peaks observed in the profile spectrum depends on the mass resolution of the mass spectrometer used for the measurement.

[0010] In a time-of-flight mass spectrometer (TOFMS), which is generally used in imaging mass spectrometers, the mass peaks appearing in the profile spectrum may have broad tails, although the mass resolution is generally relatively high. In such a case, if the difference in m / z value between a mass peak observed in a relatively wide region in the measurement region and a mass peak observed locally in a narrow region in the measurement region is small, and the signal intensity of the latter mass peak is significantly smaller than that of the former mass peak, when the mass spectrum is averaged or integrated, the mass peak with the smaller signal intensity may be buried in the tail of the mass peak with the larger signal intensity. In such a case, the mass peak observed locally does not appear in the average mass spectrum, and as a result, the user may miss important compounds that are unevenly distributed in the measurement region.

[0011] In addition, the mass resolution of a typical TOFMS may not be sufficient to separate mass peaks from different compounds with very close masses. When an average mass spectrum is created from multiple profile spectra with such insufficient separation, mass peaks with close m / z values ​​often overlap and essentially become a single mass peak. The m / z value obtained from such a mass peak may differ from the m / z value corresponding to any of the multiple overlapping compounds.

[0012] As described above, it is not rare that mass peaks originating from compounds present locally and in trace amounts on a sample cannot be observed in the average mass spectrum. In addition, the m / z value of a mass peak observed in the average mass spectrum is often different from the m / z value corresponding to a compound actually contained in the sample. For this reason, when a mass peak observed in the average mass spectrum is selected and an MS imaging image at a specific m / z value corresponding to the mass peak is displayed, the distribution of the compound that the user should observe may be inaccurate.

[0013] The present invention has been made to solve these problems, and one of its objects is to provide a mass spectrometry data analysis method and an imaging mass spectrometer that can reliably identify and confirm MS imaging images, even for compounds that are present in relatively small amounts locally within a measurement region, without overlooking their presence.

[0014] Another object of the present invention is to provide a mass spectrometry data analysis method and an imaging mass spectrometer that can display an MS imaging image of m / z values ​​that accurately correspond to compounds present in the measurement region. [Means for solving the problem]

[0015] One aspect of a mass spectrometry data analysis method according to the present invention, which has been made to solve the above problems, is a mass spectrometry data analysis method for analyzing data obtained by performing mass spectrometry on each of a plurality of micro-areas within a measurement area on a sample, comprising the steps of: an analysis region determination step of determining a plurality of analysis regions each including a plurality of the microregions by dividing the measurement region or in response to a user's designation within the measurement region; a spectrum calculation step of averaging or integrating profile spectra for each of a plurality of micro-regions included in one analytical region based on data obtained for the micro-regions in each of the plurality of analytical regions to obtain an individual integrated mass spectrum; a peak information integration step of detecting peaks in each of the plurality of individual integrated mass spectra, collecting peak information including at least the mass-to-charge ratio values ​​of the detected peaks in each of the plurality of analysis regions, and collecting the peak information of the plurality of analysis regions and arranging peaks that can be estimated to have substantially the same mass-to-charge ratio value to obtain integrated peak information; an information display step of creating and displaying a peak list or a mass spectrum based on the integrated peak information; It has the following.

[0016] In addition, one aspect of the imaging mass spectrometer according to the present invention, which has been made to solve the above problems, is a measurement unit for acquiring data by performing mass spectrometry on each of a plurality of micro-areas within a measurement area on a sample; an analysis region determination unit that determines a plurality of analysis regions each including a plurality of the microregions by dividing the measurement region or in response to a user's designation within the measurement region; a spectrum calculation unit that averages or integrates profile spectra based on data obtained by the measurement unit for a plurality of micro-areas included in each of the plurality of analysis regions to obtain an individual integrated mass spectrum; Multiple individual integrations trout a peak information integration unit that performs peak detection for each spectrum, collects peak information including at least the mass-to-charge ratio value of the detected peak in each of the plurality of analysis regions, and collects the peak information of the plurality of analysis regions, and organizes peaks that can be estimated to have substantially the same mass-to-charge ratio value to obtain integrated peak information; a display processing unit that creates a peak list or a mass spectrum based on the integrated peak information and displays it on a display unit; It is equipped with the following. Effect of the Invention

[0017] In the above-mentioned aspect of the present invention, the profile spectrum is averaged (or integrated) for each analysis area, which is a smaller area than the entire measurement area where data was collected, and integrated peak information is obtained based on the results. Therefore, it is possible to prevent peaks originating from compounds that are present locally in relatively small amounts in the measurement area from being buried in the tails of other peaks with close m / z values ​​and high intensities, and it is possible to provide the user with a peak list or mass spectrum that accurately reflects such peaks. As a result, according to the above-mentioned aspect of the present invention, the user can accurately analyze the target compound without overlooking the presence of compounds that are present locally in small amounts in a narrow range in the measurement area.

[0018] Furthermore, according to the above-mentioned aspect of the present invention, it is possible to display a mass spectrum in which peaks of m / z values ​​corresponding with high accuracy to the masses of multiple compounds present in the measurement region are observed while taking advantage of the high mass accuracy of the mass spectrometer used for the measurement. This allows the user to observe high-accuracy MS imaging images corresponding to each of the multiple compounds, and to perform more detailed and accurate compound distribution analysis than ever before. [Brief description of the drawings]

[0019] [Figure 1] 1 is a schematic block diagram of an imaging mass spectrometer according to one embodiment of the present invention; [Diagram 2] FIG. 2 is an explanatory diagram of a measurement state on a sample in the imaging mass spectrometer of the present embodiment. [Diagram 3] FIG. 4 is a diagram showing an example of the distribution state of compounds in a measurement area on a sample. [Figure 4] FIG. 4 is an explanatory diagram of an example of data analysis processing in the imaging mass spectrometer of the present embodiment. [Diagram 5] FIG. 13 is a diagram showing a modified example in which a plurality of analysis regions are set within a measurement region in the imaging mass spectrometer of the present embodiment. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] Hereinafter, an embodiment of an imaging mass spectrometer and a mass analysis data analysis method according to the present invention will be described with reference to the accompanying drawings.

[0021] FIG. 1 is a schematic block diagram of the imaging mass spectrometer of this embodiment. The imaging mass spectrometer of this embodiment includes an imaging mass spectrometer section 1, a data processing section 2, an input section 3, and a display section 4.

[0022] The imaging mass spectrometry section 1 is, for example, the measurement section of an atmospheric pressure MALDI ion trap time-of-flight mass spectrometer (APMALDI-IT-TOFMS). However, the imaging mass spectrometry section 1 may be a device that combines a laser microdissection device and a mass spectrometer that performs mass analysis on a sample prepared from a minute sample piece collected from a sample by the device, as disclosed in Patent Document 2.

[0023] The data processing unit 2 mainly has the function of processing the large amounts of data obtained by the imaging mass spectrometry unit 1, and includes as its functional blocks a data storage unit 20, a region division unit 21, a profile spectrum creation unit 22, a spectrum averaging unit 23, a peak information collection unit 24, a peak information integration unit 25, a peak list display processing unit 26, a peak selection instruction receiving unit 27, an MS imaging image creation unit 28, an image display processing unit 29, and the like.

[0024] In the imaging mass spectrometer of this embodiment, the data processing unit 2 is usually configured mainly with a personal computer or a more powerful workstation, and each of the above-mentioned functional blocks can be realized by executing dedicated data processing software (computer program) installed on the computer. In this case, the input unit 3 is a keyboard and a pointing device (such as a mouse) attached to the computer, and the display unit 4 is a display monitor.

[0025] The computer program can be provided to the user by being stored in a computer-readable non-transitory recording medium, such as a CD-ROM, a DVD-ROM, a memory card, or a USB memory (dongle). The program can also be provided to the user in the form of data transfer via a communication line such as the Internet. Furthermore, the program can be pre-installed in a computer that is a part of the system (strictly speaking, a storage device that is a part of the computer) when the user purchases the system.

[0026] An example of the data analysis process in the imaging mass spectrometer of this embodiment will be described with reference to FIGS. Fig. 2 is an explanatory diagram of the measurement state by the imaging mass spectrometry unit 1. Fig. 3 is a diagram showing an example of the distribution state of compounds in a measurement region on a sample. Fig. 4 is an explanatory diagram of an example of data analysis processing in the imaging mass spectrometer of this embodiment.

[0027] The measurement target of the imaging mass spectrometry unit 1 is, for example, a thinly sliced ​​biological tissue sample such as the brain or internal organs of an experimental animal. Such a sample is placed on a sample plate, the surface of which is coated with a matrix for MALDI, and the plate is then set at a predetermined position in the imaging mass spectrometry unit 1. 2, the imaging mass spectrometry unit 1 performs mass analysis on each of micro-areas 102 obtained by dividing a predetermined measurement area 101 set on a sample 100 into small areas in a grid pattern, and acquires mass spectrum data over a predetermined m / z range. The position, size, shape, etc. of the measurement area 101 can usually be appropriately determined by the user through optical microscope observation, etc.

[0028] A specific analysis operation is as follows. The ion source in the imaging mass spectrometry unit 1 irradiates one micro-region 102 with laser light for a short time, generating ions derived from compounds present in the micro-region 102. The generated ions are once introduced into an ion trap, and then sent to a time-of-flight mass separator where they are separated according to their m / z values ​​and then detected. This detection signal is mass spectrum data corresponding to one micro-region 102. As shown in FIG. 2, this mass spectrum data is data (profile spectrum data) that shows a continuous waveform on the m / z axis. By repeating the same analysis operation while moving the sample 100 or the ion source so that the irradiation position of the laser light moves on the sample 100, mass spectrum data can be collected for each of the micro-regions 102 set within the measurement region 101.

[0029] Note that, instead of performing a normal mass analysis on each micro-region 102, an MS / MS analysis in which ions having a specific m / z value or included in an m / z range are dissociated by collision-induced dissociation or the like and analyzed, or an MS n Analysis may be performed to obtain product ion spectral data.

[0030] A set of mass spectrum data for each microregion 102 collected as described above, i.e., MS imaging data for the entire measurement region 101, is transferred from the imaging mass spectrometry unit 1 to the data processing unit 2 and temporarily stored in the data storage unit 20. The data at this time is raw data obtained by mass spectrometry, but the data may be stored in the data storage unit 20 after appropriate waveform processing such as predetermined noise removal has been performed on this raw data.

[0031] As described above, when the MS imaging data of the entire measurement region 101 is stored in the data storage unit 20, when the user issues an instruction to execute analysis from the input unit 3, the data processing unit 2 executes the following process.

[0032] First, the area division unit 21 in the data processing unit 2 performs a process of virtually dividing one measurement area 101 into a plurality of analysis areas 103 as shown in FIG. 4(A). In the example of FIG. 4(A), the rectangular measurement area 101 is divided into six, but the number of divisions is not limited to this. The division lines do not need to be straight lines. Although the areas of the analysis areas 103 after division do not necessarily need to be the same, it is generally better not to make the difference in area too large, and one analysis area 103 includes a plurality of minute areas 102. In the example of FIG. 4, the six analysis areas 103 are labeled with the symbols #1, #2, #3, #4, #5, and #6 to distinguish them from one another.

[0033] Next, the profile spectrum creation unit 22 sequentially reads out data corresponding to all of the microregions 102 included in each analytical region 103 from the data storage unit 20, and creates a profile spectrum corresponding to each of the microregions 102. As shown in Fig. 2, the profile spectrum is a continuous waveform in the m / z axis direction, and a compound present in the microregion 102 is observed as a mountain-shaped peak.

[0034] In conventional imaging mass spectrometers, all of the profile spectra obtained in all of the microregions 102 within the measurement region 101 are averaged to calculate one average mass spectrum for the measurement region 101. In contrast, in the imaging mass spectrometer of this embodiment, the spectrum averaging unit 23 executes a process for each analysis region 103 to average the profile spectra in all of the microregions 102 included in one analysis region 103 (see FIG. 4(B)). Therefore, the same number of average mass spectra as the number of analysis regions 103, six in this example, are obtained.

[0035] 3, a relatively high concentration of compound A is present over a relatively wide range in the measurement region 101, while a relatively low concentration of compound B is present locally in a portion of the measurement region 101. In such a case, if the profile spectra in all the microregions included in the measurement region 101 are averaged, the signal intensity of the peak corresponding to compound B will be significantly lower than the signal intensity of the peak corresponding to compound A, and if the m / z values ​​of both are close, the peak corresponding to compound B may be buried in the tail of the peak corresponding to compound A.

[0036] In contrast, if the measurement region 101 is divided into multiple analysis regions 103 as shown by the dotted line in Figure 3 and the profile spectra of the microregions 102 contained in each analysis region 103 are averaged, it is more likely that the peak corresponding to compound B will be observable without being buried by the peaks of compound A in the average spectrum obtained in some of the analysis regions 103.

[0037] The peak information collecting unit 24 detects peaks from the average mass spectrum for each analysis region 103 according to a predetermined criterion (see FIG. 4(C)). Then, for each analysis region 103, information on the detected peaks is collected to create a peak list (see FIG. 4(D)). The peak information includes at least the m / z value of the peak, and may also include the intensity of the peak. As described above, since peaks derived from compound B contained locally in a part of the measurement region 101 are also observed in the average mass spectrum of some analysis regions 103, the peak list corresponding to the analysis region 103 may also include such peak information of compound B.

[0038] Next, the peak information integration unit 25 collects peak lists of all the analysis regions 103 and integrates the peak information (see FIG. 4(E)). Specifically, for example, the m / z values ​​of the peaks listed in all the peak lists are arranged in ascending order, and if the difference between the m / z values ​​of two or more adjacent peaks is within the m / z error determined according to the mass accuracy of the device used for the measurement, the peaks are considered to be from the same compound and integrated. When integrating multiple peaks with very close m / z values, the m / z value of any one of the multiple peaks before integration may be used as the m / z value of the integrated peak, or the m / z value calculated by a predetermined calculation from the m / z values ​​of the multiple peaks before integration may be used as the m / z value of the integrated peak.

[0039] The peak information integration unit 25 creates an organized peak list for the entire measurement region 101 by integrating all peaks that can be integrated as described above (see FIG. 4(F)). Peak information corresponding to a compound that is widely distributed in the measurement region 101, such as compound A shown in FIG. 3, is listed in the peak list corresponding to multiple analysis regions 103. Although the peak information may differ slightly depending on the analysis region 103, the difference should be within the error range of the mass accuracy of the device, so the peaks are integrated. On the other hand, peak information corresponding to a compound that is locally distributed in the measurement region 101, such as compound B shown in FIG. 3, is listed only in the peak list corresponding to one analysis region 103, but this will also be reflected in the integrated peak list.

[0040] The peak list display processing unit 26 displays the measurement area created as described above. 101 The entire peak list is displayed on the screen of the display unit 4. Alternatively, the peak list display processing unit 26 may create a mass spectrum (hereinafter, referred to as an integrated mass spectrum) based on the peak list created as described above, and display this integrated mass spectrum (see FIG. 4(G)).

[0041] The user checks the displayed peak list or integrated mass spectrum on the screen, and selects a desired peak on the peak list or integrated mass spectrum, for example, by indicating it with the input unit 3. The peak selection instruction receiving unit 27 recognizes the indicated peak and determines the m / z value associated with that peak.

[0042] The MS imaging image creation unit 28 reads out the signal intensity value for each microregion 102 corresponding to the determined m / z value from the data storage unit 20, and creates an MS imaging image. The image display processing unit 29 displays the created MS imaging image on the screen of the display unit 4. For example, the MS imaging image is displayed on the same screen as the peak list or integrated mass spectrum, and when the user changes the peak specified on the peak list or integrated mass spectrum, the displayed MS imaging image can be quickly updated in response to the change in the instruction (change in the specified m / z value).

[0043] As described above, the imaging mass spectrometer of this embodiment can present to the user a peak list and / or an integrated mass spectrum that fully reflects information on ion peaks derived from various compounds present globally or locally within the measurement region 101. This allows the user to appropriately select a peak that corresponds to a compound of interest on the integrated mass spectrum and confirm an MS imaging image that shows the distribution of that compound with high accuracy.

[0044] In the imaging mass spectrometer of the above embodiment, the region dividing unit 21 automatically divides the measurement region 101 into a plurality of regions according to a predetermined rule, but the user may be allowed to set the rule as appropriate. Also, instead of dividing the entire measurement region 101, it is possible to divide only a specific range designated by the user within the measurement region 101, for example, to determine a plurality of analysis regions, and then perform the above-mentioned processing on the plurality of analysis regions.

[0045] Furthermore, the user may be allowed to manually specify multiple analysis regions themselves within the measurement region 101. Fig. 5 is a diagram showing a modified example when multiple analysis regions are set within the measurement region 101 by manual operation.

[0046] For example, the region division unit 21 displays an optical microscope image of the entire measurement region 101, and accepts the user's designation of multiple analysis regions on the display screen. In the example of FIG. 5, four analysis regions 104A to 104D are designated. Here, the shape of each analysis region is rectangular, but is not limited to this. The size, position, and number of analysis regions are also arbitrary. The analysis regions 104A to 104D designated in this manner can be treated as they are in the same manner as the analysis regions after automatic division, and processing can be continued. By making it possible to set the analysis region by such manual operation, for example, a specific site (such as a biological tissue or a lesion site) that can be observed in the optical microscope image can be processed as one analysis region, which is useful for understanding compounds that are usually easy to overlook.

[0047] In the imaging mass spectrometer of the above embodiment, the imaging mass spectrometer 1 uses a time-of-flight mass separator as the mass separator, but it is not limited to the time-of-flight mass separator, and it is preferable to use a mass separator having a mass resolution equivalent to or higher than that. Specifically, in addition to various time-of-flight mass spectrometers, Fourier transform mass spectrometers using a Fourier transform ion cyclotron resonance mass separator, an orbitrap mass separator, etc. are useful. In addition, the ion source in the imaging mass spectrometer 1 is not limited to an atmospheric pressure MALDI ion source, and an ion source using any ionization method can be used.

[0048] The imaging mass spectrometry unit 1 may perform mass analysis by sequentially scanning the micro-areas 102 set in the measurement area 101 on the sample 100, but may also perform projection-type (or projection-type) imaging mass analysis in which mass analysis is performed simultaneously on a large number of micro-areas in parallel. Furthermore, the imaging mass spectrometry unit 1 may physically cut out minute sample pieces from each of the micro-areas 102 in the measurement area 101 by a technique such as laser microdissection, and obtain data by mass analyzing liquid samples prepared from each of the sample pieces. That is, the measurement technique may be any technique that can obtain mass spectrum data in a predetermined m / z range in each of the micro-areas 102 in the measurement area 101.

[0049] Furthermore, the above embodiment and modified examples are merely examples of the present invention, and it goes without saying that any appropriate modifications, corrections, additions, etc. made within the spirit of the present invention will also be encompassed within the scope of the claims of the present application.

[0050] [Various aspects] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0051] (Item 1) One aspect of the mass spectrometry data analysis method according to the present invention is a mass spectrometry data analysis method for analyzing data obtained by performing mass spectrometry on each of a plurality of micro-areas within a measurement area on a sample, comprising: an analysis region determination step of determining a plurality of analysis regions each including a plurality of the microregions by dividing the measurement region or in response to a user's designation within the measurement region; a spectrum calculation step of averaging or integrating profile spectra for each of a plurality of micro-regions included in one analytical region based on data obtained for the micro-regions in each of the plurality of analytical regions to obtain an individual integrated mass spectrum; a peak information integration step of detecting peaks in each of the plurality of individual integrated mass spectra, collecting peak information including at least the mass-to-charge ratio values ​​of the detected peaks in each of the plurality of analysis regions, and collecting the peak information of the plurality of analysis regions and arranging peaks that can be estimated to have substantially the same mass-to-charge ratio value to obtain integrated peak information; an information display step of creating and displaying a peak list or a mass spectrum based on the integrated peak information; has.

[0052] (Item 4) One aspect of the imaging mass spectrometer according to the present invention is a measurement unit for acquiring data by performing mass spectrometry on each of a plurality of micro-areas within a measurement area on a sample; an analysis region determination unit that determines a plurality of analysis regions each including a plurality of the microregions by dividing the measurement region or in response to a user's designation within the measurement region; a spectrum calculation unit that averages or integrates profile spectra based on data obtained by the measurement unit for a plurality of micro-areas included in each of the plurality of analysis regions to obtain an individual integrated mass spectrum; Multiple individual integrations trout a peak information integration unit that performs peak detection for each spectrum, collects peak information including at least the mass-to-charge ratio value of the detected peak in each of the plurality of analysis regions, and collects the peak information of the plurality of analysis regions, and organizes peaks that can be estimated to have substantially the same mass-to-charge ratio value to obtain integrated peak information; a display processing unit that creates a peak list or a mass spectrum based on the integrated peak information and displays it on a display unit; Equipped with.

[0053] In the mass analysis data analysis method described in paragraph 1 and the imaging mass spectrometer described in paragraph 4, the profile spectrum is averaged or integrated not for the entire measurement region where the data was collected, but for each analysis region which is smaller than the entire measurement region, and integrated peak information is obtained based on the results. Therefore, it is possible to prevent peaks originating from compounds that are present locally in relatively small amounts in the measurement region from being buried in the tails of other peaks with similar m / z values ​​and high intensities, and it is possible to provide a user with a peak list or mass spectrum that accurately reflects such peaks. Thus, according to the above-mentioned aspect of the present invention, the user can accurately analyze the target compound without overlooking the presence of compounds that are present locally in small amounts in a narrow range in the measurement region.

[0054] Furthermore, the mass analysis data analysis method described in paragraph 1 and the imaging mass spectrometer described in paragraph 4 can display a mass spectrum in which peaks of m / z values ​​corresponding with high accuracy to the masses of multiple compounds present in the measurement region are observed, while taking advantage of the high mass accuracy of the mass spectrometer used for the measurement. This allows the user to observe high-accuracy MS imaging images corresponding to each of the multiple compounds, and allows for more detailed and accurate compound distribution analysis than ever before.

[0055] (2) The method for analyzing mass spectrometry data according to (1) comprises: a peak selection receiving step of receiving an instruction for selecting a peak by a user on the peak list or mass spectrum displayed by the information display step; generating a mass spectrometry imaging image corresponding to the indicated peak; The present invention may further include the following:

[0056] In the peak list or mass spectrum displayed by the display step in the mass spectrometry data analysis method described in paragraph 1, highly accurate peaks corresponding to multiple compounds present in the measurement region or m / z value information of the peaks can be obtained. According to the mass spectrometry data analysis method described in paragraph 2, a user can specify a specific peak based on the peak list or mass spectrum to display an MS imaging image, so that an MS imaging image reflecting the distribution of a target compound with high accuracy can be displayed. In addition, the user can check the distribution of a compound that is present only in a small amount locally in the measurement region without overlooking the compound from the MS imaging image.

[0057] (Item 3) In the mass spectrometry data analysis method described in Item 1 or 2, the peak information integration step may include carrying out a process for determining whether or not the mass-to-charge ratio values ​​of a plurality of peaks are substantially identical, according to a criterion corresponding to the mass accuracy of an apparatus used for the mass spectrometry.

[0058] In the mass spectrometry data analysis method described in paragraph 3, by fully utilizing the high mass accuracy of the device, information on peaks originating from multiple different compounds with very close m / z values ​​can be accurately provided to the user as separate peaks. In addition, peaks that are presumed to originate from the same compound but have different m / z values ​​can be integrated and provided to the user as information on a single peak, thereby avoiding providing the user with unnecessary and redundant information. [Explanation of symbols]

[0059] 1. Imaging mass spectrometry section 2. Data processing section 20...Data storage section 21…Area division part 22...Profile spectrum creation section 23...Spectral averaging section 24…Peak Information Collection Department 25…Peak Information Integration Department 26...Peak list display processing unit 27…Peak selection instruction reception unit 28. MS Imaging Image Creation Department 29...Image display processing unit 3. Input section 4...Display section

Claims

1. A mass spectrometry data analysis method for analyzing data obtained by performing mass spectrometry on each of a plurality of micro-areas within a measurement area on a sample, comprising: an analysis region determination step of determining a plurality of analysis regions each including a plurality of the microregions by dividing the measurement region or in response to a user's designation within the measurement region; a spectrum calculation step of averaging or integrating profile spectra for each of a plurality of micro-regions included in one analytical region based on data obtained for the micro-regions in each of the plurality of analytical regions to obtain an individual integrated mass spectrum; a peak information integration step of detecting peaks in each of the plurality of individual integrated mass spectra, collecting peak information including at least the mass-to-charge ratio values ​​of the detected peaks in each of the plurality of analysis regions, and collecting the peak information of the plurality of analysis regions and arranging peaks that can be estimated to have substantially the same mass-to-charge ratio value to obtain integrated peak information; an information display step of creating and displaying a peak list or a mass spectrum based on the integrated peak information; A mass spectrometry data analysis method comprising the steps of:

2. a peak selection receiving step of receiving an instruction for selecting a peak by a user on the peak list or mass spectrum displayed by the information display step; generating a mass spectrometry imaging image corresponding to the indicated peak; The method of claim 1 , further comprising:

3. 2. The mass spectrometry data analysis method according to claim 1, wherein the peak information integration step includes a process for determining whether the mass-to-charge ratio values ​​of a plurality of peaks are substantially identical in accordance with a criterion corresponding to the mass accuracy of an apparatus used for the mass spectrometry.

4. a measurement unit for acquiring data by performing mass spectrometry on each of a plurality of micro-areas within a measurement area on a sample; an analysis region determination unit that determines a plurality of analysis regions each including a plurality of the microregions by dividing the measurement region or in response to a user's designation within the measurement region; a spectrum calculation unit that averages or integrates profile spectra based on data obtained by the measurement unit for a plurality of micro-areas included in each of the plurality of analysis regions to obtain an individual integrated mass spectrum; a peak information integration unit that performs peak detection for each of the plurality of individual integrated mass spectra, collects peak information including at least the mass-to-charge ratio value of the detected peak in each of the plurality of analysis regions, and collects the peak information of the plurality of analysis regions and organizes peaks that can be estimated to have substantially the same mass-to-charge ratio value to obtain integrated peak information; a display processing unit that creates a peak list or a mass spectrum based on the integrated peak information and displays it on a display unit; An imaging mass spectrometer comprising:

Images