Imaging analysis method and device using ion mobility mass analysis

Abstract

An image analysis device according to one aspect of the present invention is provided with: a measurement unit that acquires analysis result data by performing ion mobility mass analysis on each of a plurality of minute regions within a predetermined measurement region in a sample; a correlation investigation unit (22, 23) that, on the basis of analysis result data acquired by the measurement unit, investigates the correlation between m / z and ion mobility in the data; and a data reduction unit (24, 25) that reduces the amount of analysis result data by defining an ion mobility range in accordance with m / z or defining an m / z range in accordance with the ion mobility on the basis of the correlation result obtained by the correlation investigation unit.

Description

Technical Field

[0001] The present invention relates to an imaging analysis method and device using ion mobility spectrometry (Ion Mobility Spectrometry-Mass Spectrometry) as an analysis technique. Background Art

[0002] As described in Patent Document 1, etc., in an imaging mass spectrometer, mass spectrum data within a predetermined mass-to-charge ratio (m / z) range is generally obtained for each micro region obtained by finely dividing a two-dimensional measurement region on a sample. If the position information such as the two-dimensional coordinates of a micro region on a sample is treated as information along one axis, the data obtained by the imaging mass spectrometer is as follows: Figure 3 The ion intensity data shown in (A) is a two-dimensional representation of two parameters, one axis is position information and the other axis is m / z value (mass spectrum information). In this case, the mass spectrum data obtained for a certain micro region within the measurement area is Figure 3 (A) shows the ion intensity data along the horizontal line A.

[0003] In mass analysis, it is in principle impossible to separate and detect a certain compound and its structural isomers with the same mass. In contrast, in recent years, ion mobility mass spectrometers that use both ion mobility analysis and mass analysis to separate ions based on collision cross-sectional areas have been put into practical use. Patent Document 2 and Non-Patent Document 1 disclose an ion mobility mass spectrometer that is equipped with an orthogonal acceleration time-of-flight mass spectrometer at the rear stage of an ion mobility separation unit.

[0004] In such an ion mobility mass spectrometer, after separating ions from sample components according to ion mobility, multiple ions having the same degree of ion mobility can be separated and detected according to m / z. Therefore, when the ion mobility mass spectrometer is used for imaging analysis, the measurement data obtained by the device is as follows: Figure 3 The 3D ion intensity data shown in (B) is represented by three parameters: the first axis is position information, the second axis is m / z value (mass spectrum information), and the third axis is ion mobility (or collision cross-sectional area, drift time, etc.). In this case, the measurement data containing the mass spectrum and ion mobility spectrum obtained in a certain micro-region within the measurement area as information is, Figure 3 (B) shows the ion intensity data present on plane B.

[0005] In the following description, an apparatus that uses an ion mobility mass spectrometer in imaging analysis is referred to as an imaging ion mobility mass spectrometer, or simply referred to as imaging I MS-MS. In addition, a general imaging mass spectrometer may be referred to as imaging MS.

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Application Publication No. 2011-191222

[0009] Patent Document 2: International Publication No. 2015 / 053039

[0010] Non-patent literature

[0011] Non-patent literature 1: Yun Wang Alel Yunas et al., “Building a Collision Cross Section Library of Pharmaceutical Drugs Using the Vion IMS QTof Platform: Verification of System Performance, Precision and Deviation of CCS Measurements”, [retrieved on July 4, 2022], Waters Corporation, USA, Internet<URL:https: / / www.waters.com / webassets / cms / library / docs / 720005903en.pdf>

[0012] Non-patent document 2: “IMAGEREVALTM MS MS imaging analysis software”, [retrieved on July 7, 2022], Shimadzu Corporation, Internet<URL:https: / / www.an.shimadzu.co.jp / bio / imagereveal / features.htm> Summary of the invention

[0013] Technical problem to be solved by the invention

[0014] In imaging IMS-MS, the dimension of the measured data increases by one compared to imaging MS. Therefore, the amount of data to be processed in the analysis process increases significantly. As an example, assume that the number of elements in each dimension is 10. 4The total number of measurement data acquired in imaging IMS-MS is 10 4 ×10 4 ×10 4 =10 12 When the digital data format is set to the double type (double-precision floating point type) used in standard, the capacity of one measurement data is 8 bytes, so the total amount of measurement data is 8×10 12 byte = 8TB. ​​This is a considerable amount of data for data processing in a current standard personal computer (PC). In addition, if the dimension of the measurement data increases, the calculation of data analysis processing, such as searching for images with similar distribution or performing difference analysis of multiple images, becomes complicated, so the capacity of the RAM (Random access memory) used in the calculation process also increases.

[0015] Therefore, in order to perform analysis processing on the measurement data acquired by imaging IMS-MS, a high-performance and expensive PC is required. If a general PC is used, there may be a problem such as insufficient resources or an extremely low processing speed, which may cause the processing to take a long time.

[0016] The present invention has been made in view of such technical problems, and one of its main objects is to reduce the load of data processing in imaging IMS-MS.

[0017] Solutions for solving the above technical problems

[0018] A first aspect of the imaging analysis method using ion mobility mass spectrometry of the present invention is a method for analyzing analysis result data obtained by performing ion mobility mass spectrometry on a plurality of micro-regions within a predetermined measurement region in a sample, comprising:

[0019] A correlation investigation step, based on the acquired analysis result data, investigating the correlation between the mass-to-charge ratio and the ion mobility in the data; and

[0020] The data reduction step is to reduce the amount of analysis result data by limiting the ion mobility range according to the mass-to-charge ratio or limiting the mass-to-charge ratio range according to the ion mobility based on the correlation result obtained in the correlation investigation step.

[0021] Furthermore, a first aspect of the imaging analysis device using ion mobility mass spectrometry of the present invention is an apparatus for implementing the imaging analysis method of the first aspect, comprising:

[0022] A measuring unit that acquires analysis result data by performing ion mobility mass analysis on a plurality of micro-regions within a predetermined measurement region in the sample;

[0023] a correlation investigation unit that investigates the correlation between the mass-to-charge ratio and the ion mobility in the analysis result data acquired by the measurement unit; and

[0024] The data reduction unit reduces the amount of analysis result data by limiting the ion mobility range according to the mass-to-charge ratio or limiting the mass-to-charge ratio range according to the ion mobility based on the correlation result obtained by the correlation investigation unit.

[0025] Furthermore, a second aspect of the imaging analysis method using ion mobility mass spectrometry of the present invention is an analysis method for analyzing analysis result data obtained by performing ion mobility mass spectrometry on a plurality of micro-regions within a predetermined measurement region in a sample, comprising:

[0026] a data extraction step of performing peak detection on the acquired analysis result data in each micro-region and extracting the analysis result data corresponding to the peak; and

[0027] In the dimension aggregation step, in each micro region, the two-dimensional axes of mass-to-charge ratio and ion mobility are aggregated into a one-dimensional axis using the correlation between the mass-to-charge ratio and the ion mobility in the analysis result data extracted in the data extraction step.

[0028] Furthermore, a second embodiment of the imaging analysis device using ion mobility mass spectrometry of the present invention is a device for implementing the imaging analysis method of the second embodiment, comprising:

[0029] A measuring unit that acquires analysis result data by performing ion mobility mass analysis on a plurality of micro-regions within a predetermined measurement region in the sample;

[0030] a data extraction unit that performs peak detection on the acquired analysis result data in each micro region and extracts the analysis result data corresponding to the peak; and

[0031] The dimensional aggregation unit aggregates the two-dimensional axes of mass-to-charge ratio and ion mobility into a one-dimensional axis for each micro region using the correlation between the mass-to-charge ratio and ion mobility in the analysis result data extracted by the data extraction unit.

[0032] Effects of the Invention

[0033] According to the imaging analysis method and apparatus using ion mobility mass spectrometry of the first scheme, the total amount of analysis result data can be reduced by limiting the range of ion mobility or mass-to-charge ratio. In addition, according to the imaging analysis method and apparatus using ion mobility mass spectrometry of the second scheme, after reducing the total amount of analysis result data by performing peak detection, the dimensionality of the data can be further reduced. As a result, according to the present invention, the load of data processing for image analysis, differential analysis, etc. in a PC can be reduced, for example, the performance or specifications of the PC required for data processing can be reduced, or the processing speed can be increased and the processing time can be shortened when the same PC is used. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a schematic diagram of the configuration of an imaging IMS-MS as the first embodiment of the present invention.

[0035] Figure 2 This is a functional block diagram of the data processing unit of the imaging IMS-MS according to the first embodiment.

[0036] Figure 3 : is a diagram showing a comparison of the dimensions of parameters of measurement data obtained by imaging MS and measurement data obtained by imaging IMS-MS.

[0037] Figure 4 This is a schematic diagram showing the relationship between m / z value and ion mobility in measurement data obtained by imaging IMS-MS.

[0038] Figure 5 This is a conceptual diagram showing the data amounts before and after data reduction in the imaging IMS-MS according to the first embodiment.

[0039] Figure 6 This is a functional block diagram of a data processing unit of an imaging IMS-MS as a second embodiment.

[0040] Figure 7 It is an explanatory diagram of the dimensional aggregation process in the imaging IMS-MS as the second embodiment.

[0041] Figure 8 This is a diagram showing an example of a pseudo mass spectrum obtained by imaging analysis in the imaging IMS-MS according to the first embodiment.

[0042] Fig. 9 This is a diagram showing an example of a pseudo mass spectrum obtained by imaging analysis in the imaging IMS-MS according to the second embodiment.

[0043] Fig.10 This is a diagram showing an example of a table for associating peak IDs, ion mobilities, and m / z values ​​in the imaging IMS-MS according to the second embodiment. DETAILED DESCRIPTION

[0044] Hereinafter, an imaging IMS-MS and an imaging analysis method in the device as an embodiment of the present invention will be described with reference to the drawings.

[0045] [First embodiment]

[0046] Figure 1 This is a schematic block diagram of the imaging IMS-MS according to the first embodiment. Figure 2 This is a functional block diagram of a data processing unit in the imaging IMS-MS according to the first embodiment.

[0047] like Figure 1 As shown, the IMS-MS of the first embodiment includes a measuring unit 1 , a data processing unit 2 , an input unit 3 , and a display unit 4 .

[0048] The measuring unit 1 performs ion mobility mass analysis on a sliced ​​sample 100 obtained by thinly slicing an organ or the like taken from a biological body such as an experimental animal to obtain measurement data. As an example, it is an atmospheric pressure MALDI (matrix-assisted laser desorption ionization) ion mobility-orthogonal acceleration time-of-flight mass spectrometer (APMALDI-IMS-OATOFMS). In this case, the measuring unit 1 includes: a laser irradiation unit 10, which irradiates a micro-diameter laser to the sample 100 for ionization based on the atmospheric pressure MALDI method; an ion mobility separation unit (IMS unit) 11, which separates ions generated from the sample 100 by irradiation with the laser according to ion mobility; and a mass spectrometry unit (MS unit) 12, which separates and detects the separated ions according to m / z.

[0049] Alternatively, the measuring unit 1 may be a device that combines a device for collecting a plurality of fine sample pieces from a sample by laser microdissection or the like, and a device for performing ion mobility mass spectrometry on a sample prepared from each of the collected sample pieces.

[0050] The data processing unit 2 has a function of processing a large amount of measurement data obtained by the measurement unit 1, and includes a measurement data storage unit 20, an IMS range limiting unit 21, a reduced data storage unit 26, a parameter conversion unit 27, an imaging data analysis unit 28, a display processing unit 29, etc. as functional blocks. The IMS range limiting unit 21 includes a peak detection unit 22, a correlation investigation unit 23, an ion mobility range determination unit 24, and a measurement data reduction unit 25 as lower functional blocks.

[0051] In the imaging IMS-MS of this embodiment, the data processing unit 2 is usually composed of a PC or a higher-performance workstation as the center, and the above-mentioned functional blocks can be specifically implemented by executing dedicated data processing software (computer program) installed in the computer. In this case, the input unit 3 is a keyboard or pointing device (mouse, etc.) attached to the computer, and the display unit 4 is a display monitor.

[0052] The computer program can be stored in a non-temporary recording medium such as a CD-ROM, a DVD-ROM, a memory card, a USB memory (dongle) and provided to the user. In addition, the program can also be provided to the user in the form of data transmission via a communication line such as the Internet. In addition, the program can also be pre-installed in a computer that is part of the system (strictly speaking, a storage device that is part of the computer) at the time when the user purchases the system.

[0053] The measuring operation of the measuring unit 1 will be briefly described.

[0054] The sample 100 to be measured is placed on a sample plate (not shown), and a matrix for MALDI analysis is applied to the surface of the sample plate and placed at a predetermined position of the measuring unit 1. The measuring unit 1 performs ion mobility mass analysis on each micro-region 102 obtained by finely dividing the predetermined measurement region 101 set on the sample 100 in a grid shape. That is, in the measuring unit 1, the laser irradiation unit 10 irradiates a laser beam to one micro-region 102 for a short time. The compound present in the micro-region 102 is ionized by the irradiation of the laser beam.

[0055] Ions generated from the sample 100 are introduced into the ion mobility separation unit 11 and spatially separated according to ion mobility. The various ions separated according to ion mobility are divided into a plurality of ions included in a predetermined ion mobility range (a range that can be regarded as substantially the same degree) and sequentially sent to the mass separation unit 12. Then, the plurality of ions divided together are separated according to m / z in the mass separation unit 12 and detected.

[0056] In the mass separation unit 12, mass analysis is repeatedly performed on an ion packet consisting of a plurality of ions included in an ion mobility range that can be regarded as having substantially the same ion mobility. Thus, measurement data corresponding to a micro region 102 on the sample 100, i.e., having position information on the sample 100, and having two parameters of ion mobility and m / z is obtained. That is, the measurement data is ion mobility spectrum data showing the relationship between ion mobility and ion intensity, and is also mass spectrum data showing the relationship between m / z value and ion intensity.

[0057] The measuring unit 1 moves the sample 100 in the XY plane by a driving unit (not shown) to move the laser irradiation position on the sample 100, and repeats the same measurement operation. Thus, measurement data is collected for all micro-areas 102 set in the measurement area 101 on the sample 100. In addition, the user can usually appropriately set the position, size, shape, etc. of the measurement area 101 on the sample 100 by optical microscopic observation or the like.

[0058] The measurement data collected in each micro region 102 through the above-mentioned measurement is transmitted from the measurement unit 1 to the data processing unit 2 and temporarily stored in the measurement data storage unit 20. Figure 5 As shown in (A), the measurement data obtained for a sample 100 (or a measurement area 101) is 3D ion intensity data having three parameters: position information of a micro-area 102 (e.g., position coordinates (X, Y)), ion mobility, and m / z. The amount of axial measurement data of the position information depends on the number of micro-areas 102. The amount of axial measurement data of m / z depends on the m / z range of the measurement object and the step size of the m / z value within the range. The amount of axial measurement data of ion mobility depends on the ion mobility range of the measurement object and the step size of the ion mobility value within the range.

[0059] In the data processing unit 2, based on the measurement data, in addition to producing an image showing the ion intensity distribution at a specific m / z value or a specific ion mobility, an analysis process for searching for m / z values ​​or ion mobility values ​​showing a characteristic distribution, or searching for a plurality of m / z values ​​or ion mobility values ​​having similar ion intensity distributions is performed. Here, in the analysis process of such data, imaging mass analysis data analysis software described in non-patent document 2 and the like is used, but if the measurement data obtained by measurement is to be directly processed, the following problem occurs.

[0060] (1) Compared with the imaging quality analysis data, the dimension of the parameter is increased by one, so the total amount of measurement data is large, and the processing load in a standard PC is too large.

[0061] (2) The imaging quality analysis data analysis software described above is used to analyze Figure 3 The processing of the two-dimensional ion intensity data having two parameters, position information and m / z, shown in (A) is premised on the processing of the two-dimensional ion intensity data, and therefore the three-dimensional ion intensity data having three parameters cannot be directly processed.

[0062] On the other hand, in the imaging IMS-MS according to the first embodiment, analysis is performed after performing the following data processing based on the measurement data.

[0063] Ion mobility is proportional to the collision cross-sectional area of ​​the ion, which is related to the mass of the ion. Therefore, as shown in Non-Patent Document 1, there is a correlation between ion mobility and m / z value. Therefore, the ion mobility and m / z in the measurement data obtained by IMS-MS can be roughly included in Figure 4 The range R indicated by the oblique lines is a range R having a width Q with the straight line P as the center line. In other words, it can be considered that there is no meaningful measurement data outside the range R. Therefore, in the imaging IMS-MS of the first embodiment, the correlation between the ion mobility and the m / z value is utilized to delete the measurement data assumed to be meaningless, thereby reducing the total amount of data.

[0064] Specifically, first, in order to investigate the correlation between ion mobility and m / z value, the peak detection unit 22 of the IMS range limiting unit 21 uses the acquired measurement data to detect the peaks in each micro region. Figure 3 The peak of ion intensity on plane B shown in (B) is obtained, and the combination of ion mobility value and m / z value where the peak appears is obtained as peak information. The correlation investigation unit 23 performs regression analysis using the obtained multiple peak information and calculates the regression line showing the most likely relationship between ion mobility and m / z. The regression line is Figure 4 The straight line P in .

[0065] Furthermore, the ion mobility range determination unit 24 calculates the width Q as a function of the m / z value from the dispersion degree of the peak obtained as a result of the regression analysis. Thus, the range R in which the measurement data is allowed to exist is determined. Then, the measurement data reduction unit 25 reduces the range of the ion mobility, which is one of the parameters in the acquired measurement data, according to the m / z value, and deletes the measurement data having the ion mobility outside the range, thereby reducing the total amount of the measurement data. The range in which the measurement data exists after the reduction is as follows: Figure 5 As shown in (B). Figure 5 The black cube in (A) is within the range of Figure 5 The measured data of the parameters outside the range of the three-dimensional object painted black in (B) are deleted. However, most of the measured data that are actually deleted are zero data or noise data, and do not substantially affect the analysis results described later.

[0066] For example, in the above example, the number of elements in each dimension is 10 4 The number of elements of ion mobility was limited to 10 for each m / z value. 2 In this case, the total number of measurement data is 10 4 ×10 4 ×10 2 =10 10That is, the total amount of measurement data is compressed to 1 / 100 compared to the case where data reduction is not performed. The reduced measurement data is temporarily stored in the reduced data storage unit 26 .

[0067] In addition, Figure 5 In the case shown in (A), the range of ion mobility is the same regardless of the m / z value, but Figure 5 In the case shown in (B), the range of ion mobility depends on the m / z value. Figure 4 The equation representing the straight line P and the value of the width Q, or information equivalent thereto, are associated with the reduced measurement data. Using this information, the value of the ion mobility can be obtained from the m / z value and the position in the ion mobility range (width Q), for example.

[0068] In the above data reduction method, although the number of parameters, that is, the dimensionality of the measurement data, is not reduced, the total amount of measurement data is reduced, and the load on the PC is reduced. However, as mentioned above, in order to perform data processing in the analysis software based on processing two-dimensional ion intensity data, it is necessary to treat the two parameters of m / z value and ion mobility as one parameter for convenience.

[0069] Therefore, before the analysis process, for convenience, the parameter conversion unit 27 converts the two parameters of ion mobility and m / z value in each measurement data into a combined parameter. As an example, the decimal points of the numerical values ​​of ion mobility and m / z value are discarded (or rounded off), and on this basis, the numerical value of the integer part is assigned to the numerical value of ion mobility, and the numerical value of the part after the decimal point is assigned to the numerical value of m / z, so that it can be conveniently processed as a parameter. For example, in the case where there is an ion peak with an ion mobility (collision cross-sectional area) of 200 [ccs] and an m / z value of 300, it can be expressed as a numerical value such as "200.300". Alternatively, it is also possible not to use a decimal point, and to assign the numerical values ​​of the number of digits from the highest digit to a specific digit in the numerical value of the specified digits to the ion mobility, and to assign the numerical values ​​of the remaining digits to m / z. For example, when the first 4 digits of an 8-digit numerical value are assigned to ion mobility and the last 4 digits are assigned to m / z, an ion peak with an ion mobility (collision cross-sectional area) of 200 [ccs] and an m / z value of 300 is represented by a numerical value such as "02000300".

[0070] The imaging data analysis unit 28 reads the measurement data obtained by changing the ion mobility and m / z value for convenience as described above, and performs data processing instructed by the user through the input unit 3. For example, when making an imaging image showing the distribution of a compound having a specific m / z value and a specific ion mobility, the measurement data of each micro area having a parameter value for convenience obtained by combining the specific m / z value and the ion mobility is extracted, and an image is made based on the value (ion intensity value) of the measurement data. The display processing unit 29 displays the image made in this way on the screen of the display unit 4 and provides it to the user.

[0071] Furthermore, the imaging data analysis unit 28 can create a spectrum along the converted parameter axis similar to the mass spectrum in a micro region at a specific position by processing the measurement data in the same manner as when analyzing imaging mass analysis data. Figure 8 is an example of such a spectrum, and the horizontal axis is a new parameter axis obtained by combining the ion mobility and the m / z value for convenience. From the spectrum data thus obtained, only the integer part of the horizontal axis is extracted, and the intensities of multiple peaks with the same numerical value are added to make a new spectrum, thereby obtaining the ion mobility spectrum in the micro region. In addition, only the numerical value after the decimal point of the horizontal axis is extracted from the above-mentioned spectrum data, and the intensities of multiple peaks with the same numerical value are added to make a new spectrum, thereby obtaining the mass spectrum in the micro region.

[0072] [Second embodiment]

[0073] Next, an imaging IMS-MS according to a second embodiment having a different data reduction method from the first embodiment will be described. The configuration of the measurement unit 1 is the same as that of the first embodiment, so the description is omitted, and the configuration and processing operation of the data processing unit different from the first embodiment will be described.

[0074] Figure 6 This is a functional block diagram of the data processing unit 2B in the imaging IMS-MS of the second embodiment. The data processing unit 2B includes a measurement data storage unit 200, a peak detection unit 201, an IMS-MS dimension aggregation unit 202, a parameter conversion unit 203, a reduced data storage unit 204, an imaging data analysis unit 205, a display processing unit 206, etc. as functional blocks.

[0075] In the imaging IMS-MS of this embodiment, the peak detection unit 201 performs peak detection on the plane of ion mobility and m / z value for each micro region for the measurement data of all micro regions, and obtains peak information including the ion mobility and m / z value of the peak, and the peak intensity. This processing is substantially the same as the processing performed by the peak detection unit 22 in the first embodiment. However, in this second embodiment, the amount of data is reduced by retaining only the measurement data corresponding to the detected peak.

[0076] Next, the IMS-MS dimension aggregation unit 202 aggregates the two dimensions of ion mobility and m / z value into one dimension for each of the multiple peaks detected in each micro region to obtain a new axis. Specifically, for example, first, in each micro region, Figure 7 As shown in FIG. 1 , using multiple peaks located on the orthogonal axes of the ion mobility axis and the m / z axis, regression analysis is performed to obtain a regression line. The regression line is a new axis after the dimensions are aggregated. Then, as Figure 7 As shown in the example, a line orthogonal to the new axis is drawn from the plotted points corresponding to each peak, and the position of the intersection of the line and the new axis is determined as a new variable corresponding to the plotted point on the new axis. In other words, the variables after dimension aggregation are obtained by projecting the plotted points corresponding to each peak onto the regression line. This is essentially the same dimension aggregation technique as principal component analysis.

[0077] The above-mentioned new axis is an axis that mixes ion mobility and m / z value, but the numerical value on this axis is different from both ion mobility and m / z value. In addition, the original ion mobility and m / z value cannot be inversely calculated based on the numerical value on this new axis. That is, the above-mentioned processing is an irreversible conversion operation. Therefore, in this case, it is necessary to prepare information that associates the numerical value on the new axis with the original ion mobility and m / z value.

[0078] Therefore, the parameter conversion unit 203 determines a variable on a new axis for each measurement data, and creates information that associates the variable with the original ion mobility and m / z value. As an example, the parameter conversion unit 203 assigns a unique ID (e.g., a sequential number) to each detected peak, and sets the ID as the value of the variable on the new axis. Then, a data item such as Fig.10 The measurement data whose data volume is reduced in this way and whose parameter dimensions are reduced from three dimensions to two dimensions, and the table in which the IDs are associated with the ion mobilities and m / z values ​​are stored in the reduced data storage unit 204 .

[0079] When the user instructs the execution of analysis processing via the input unit 3, the imaging data analysis unit 205 reads the measurement data from the reduced data storage unit 204 and executes the instructed data processing. In this case, when the mass spectrum is displayed by data analysis, as shown in FIG. Fig. 9 As shown, the IDs are sequentially arranged on the m / z axis, and a pseudo mass spectrum showing peaks corresponding to the ID values ​​can be displayed, similarly to a mass spectrum. Based on the ID values ​​in the pseudo mass spectrum displayed in this way, the ion mobility and the m / z value are obtained by referring to the above-mentioned correlation table, and each graph with the horizontal axis set to the ion mobility or the m / z value is drawn, thereby obtaining an ion mobility spectrum and a mass spectrum.

[0080] In the parameter conversion unit 203, instead of assigning a unique ID to each peak as described above, Figure 7 As shown, an appropriate scale is determined along the new axis as the regression line obtained, and the numerical values ​​on the axis corresponding to each peak are determined according to the scale. In this case, a table is also prepared that associates the numerical values ​​on the new axis with the original ion mobility and m / z value. For example, in the case of an ion peak with an ion mobility (collision cross-sectional area) of 200 [ccs] and m / z 300, the numerical value corresponding to the peak on the new axis is set to 123. In this case, when the mass spectrum is displayed by data analysis, a pseudo mass spectrum can be made in a manner that the peak is observed at m / z 123.

[0081] In addition, for example, when a compound corresponding to a detected peak is determined by identification processing, Fig.10 In that case, when creating a pseudo mass spectrum, the compound name may be recorded along the horizontal axis instead of the ID, and the peak may be plotted at the position of the compound name.

[0082] The above-described embodiment is merely an example of the present invention, and any appropriate changes, modifications, additions, etc., within the scope of the gist of the present invention are naturally included in the claims of the present application.

[0083] [Various options]

[0084] Those skilled in the art will appreciate that the above exemplary embodiments are specific examples of the following schemes.

[0085] (Item 1) One embodiment of the imaging analysis method using ion mobility mass spectrometry of the present invention is a method for analyzing analysis result data obtained by performing ion mobility mass spectrometry on a plurality of micro-regions within a predetermined measurement region in a sample, comprising:

[0086] A correlation investigation step, based on the acquired analysis result data, investigating the correlation between the mass-to-charge ratio and the ion mobility in the data; and

[0087] The data reduction step is to reduce the amount of analysis result data by limiting the ion mobility range according to the mass-to-charge ratio or limiting the mass-to-charge ratio range according to the ion mobility based on the correlation result obtained in the correlation investigation step.

[0088] (Item 3) In addition, one embodiment of the imaging analysis device using ion mobility mass spectrometry of the present invention comprises:

[0089] A measuring unit that acquires analysis result data by performing ion mobility mass analysis on a plurality of micro-regions within a predetermined measurement region in the sample;

[0090] a correlation investigation unit that investigates the correlation between the mass-to-charge ratio and the ion mobility in the analysis result data acquired by the measurement unit; and

[0091] The data reduction unit reduces the amount of analysis result data by limiting the ion mobility range according to the mass-to-charge ratio or limiting the mass-to-charge ratio range according to the ion mobility based on the correlation result obtained by the correlation investigation unit.

[0092] (Item 5) In addition, another embodiment of the imaging analysis method using ion mobility mass spectrometry of the present invention is a method for analyzing analysis result data obtained by performing ion mobility mass spectrometry on a plurality of micro-regions within a predetermined measurement region in a sample, comprising:

[0093] a data extraction step of performing peak detection on the acquired analysis result data in each micro-region and extracting the analysis result data corresponding to the peak; and

[0094] In the dimension aggregation step, in each micro region, the two-dimensional axes of mass-to-charge ratio and ion mobility are aggregated into a one-dimensional axis using the correlation between the mass-to-charge ratio and the ion mobility in the analysis result data extracted in the data extraction step.

[0095] (Item 8) In addition, another embodiment of the imaging analysis device using ion mobility mass spectrometry of the present invention comprises:

[0096] A measuring unit that acquires analysis result data by performing ion mobility mass analysis on a plurality of micro-regions within a predetermined measurement region in the sample;

[0097] a data extraction unit that performs peak detection on the acquired analysis result data in each micro region and extracts the analysis result data corresponding to the peak; and

[0098] The dimensional aggregation unit aggregates the two-dimensional axes of mass-to-charge ratio and ion mobility into a one-dimensional axis for each micro region using the correlation between the mass-to-charge ratio and ion mobility in the analysis result data extracted by the data extraction unit.

[0099] According to the imaging analysis method described in item 1 or item 5, the total amount of analysis result data can be reduced by limiting the range of ion mobility or mass-to-charge ratio. In addition, according to the imaging analysis device described in item 3 or item 7, after reducing the total amount of analysis result data by performing peak detection, the dimension of the data can be further reduced. As a result, according to these analysis methods or analysis devices, the load of data processing such as image analysis and differential analysis in a PC can be reduced, for example, the performance or specifications of the PC required for data processing can be reduced, or the processing speed can be increased and the processing time can be shortened when the same PC is used.

[0100] (Item 2) The imaging analysis method using ion mobility mass spectrometry described in Item 1 can be set to also have a parameter conversion step, in which, for the reduced analysis result data in the data reduction step, the values ​​of ion mobility and mass-to-charge ratio as parameters of each data are converted into temporary parameters summarized into one numerical value.

[0101] (Item 4) In addition, the imaging analysis device using ion mobility mass spectrometry described in Item 3 can be configured to further include a parameter conversion unit that converts the values ​​of ion mobility and mass-to-charge ratio as parameters of each data into temporary parameters summarized into one numerical value for the analysis result data after reduction by the data reduction unit.

[0102] In the analysis method described in item 2 and the analysis device described in item 4, for example, a specific multi-digit value in a multi-digit value can be assigned to the ion mobility, and the remaining multi-digit values ​​can be assigned to the mass-to-charge ratio. Alternatively, the integer part of the value can be assigned to the ion mobility, and the value after the decimal point can be assigned to the mass-to-charge ratio.

[0103] According to the analysis method described in item 2 and the analysis device described in item 4, analysis result data having three-dimensional parameters such as position information, ion mobility, and mass-to-charge ratio can be processed as analysis result data having two-dimensional parameters. Thus, existing imaging mass analysis data analysis software based on the premise that the parameters are two-dimensional can be used for analysis processing.

[0104] (Item 6) In addition, the imaging analysis method described in Item 5 can be set to also have a variable conversion step, assigning a new variable along the one-dimensional axis to each of the extracted analysis result data, and producing information showing the correspondence between the value of the variable and the original ion mobility and mass-to-charge ratio.

[0105] (Item 7) In addition, the imaging analysis method described in Item 5 can be set to further include a variable conversion step, in which an inherent number is assigned to each of the extracted analysis result data, and information showing the correspondence between the inherent number and the original ion mobility and mass-to-charge ratio is produced.

[0106] (Item 9) In addition, the imaging analysis device described in Item 8 can be configured to further include a variable conversion unit that assigns a new variable along the one-dimensional axis to each of the extracted analysis result data, and produces information showing the correspondence between the value of the variable and the original ion mobility and mass-to-charge ratio.

[0107] (Item 10) In addition, the imaging analysis device described in Item 8 can be configured to further include a variable conversion unit for assigning an inherent number to each of the extracted analysis result data and producing information showing the correspondence between the inherent number and the original ion mobility and mass-to-charge ratio.

[0108] According to the analysis device described in any one of Item 6, Item 7, Item 9, or Item 10, it is possible to perform analysis processing using existing imaging mass analysis data analysis software that assumes that parameters are two-dimensional.

[0109] Description of Reference Numerals

[0110] 1 Measurement Department

[0111] 10 Laser irradiation section

[0112] 11 Ion Mobility Separation Unit (IMS Unit)

[0113] 12 Mass separation unit (MS unit)

[0114] 2.2B Data Processing Department

[0115] 20, 200 Measurement data storage unit

[0116] 21 IMS Range Limitation Department

[0117] 22, 201 Peak Detection Unit

[0118] 23 Relevance Investigation Department

[0119] 24 Ion mobility range determination unit

[0120] 25 Measurement data reduction section

[0121] 26, 204 Reduction of data storage department

[0122] 27, 203 Parameter conversion unit

[0123] 28, 205 Imaging Data Analysis Department

[0124] 29, 206 Display Processing Unit

[0125] 202 IMS-MS Dimension Summary Department

[0126] 3 Input section

[0127] 4 Display

[0128] 100 samples

[0129] 101 Measurement area

[0130] 102 micro-areas.

Claims

1. An imaging analysis method using ion mobility mass spectrometry, which is a method for analyzing analysis result data obtained by performing ion mobility mass spectrometry on a plurality of micro-regions within a predetermined measurement region in a sample, characterized in that: have: A correlation investigation step, based on the obtained analysis result data, investigating the correlation between the mass-to-charge ratio and the ion mobility in the data; as well as The data reduction step is to reduce the amount of analysis result data by limiting the ion mobility range according to the mass-to-charge ratio or limiting the mass-to-charge ratio range according to the ion mobility based on the correlation result obtained in the correlation investigation step.

2. The imaging analysis method using ion mobility mass spectrometry according to claim 1, characterized in that: The method further comprises a parameter conversion step of converting the values ​​of ion mobility and mass-to-charge ratio as parameters of each data into a temporary parameter obtained by summarizing the values ​​into one numerical value for the analysis result data reduced in the data reduction step.

3. An imaging analysis device using ion mobility mass spectrometry, characterized in that: have: A measuring unit that acquires analysis result data by performing ion mobility mass analysis on a plurality of micro-regions within a predetermined measurement region in the sample; a correlation investigation unit that investigates the correlation between the mass-to-charge ratio and the ion mobility in the analysis result data acquired by the measurement unit; as well as The data reduction unit reduces the amount of analysis result data by limiting the ion mobility range according to the mass-to-charge ratio or limiting the mass-to-charge ratio range according to the ion mobility based on the correlation result obtained by the correlation investigation unit.

4. The imaging analysis device using ion mobility mass spectrometry according to claim 3, characterized in that: The method further comprises a parameter conversion unit for converting the values ​​of ion mobility and mass-to-charge ratio as parameters of each data into a temporary parameter obtained by summarizing the values ​​into one numerical value for the analysis result data reduced by the data reduction unit.

5. An imaging analysis method using ion mobility mass spectrometry, which is a method for analyzing analysis result data obtained by performing ion mobility mass spectrometry on a plurality of micro-regions within a predetermined measurement region in a sample, characterized in that: have: A data extraction step, performing peak detection on the acquired analysis result data in each micro-region, and extracting the analysis result data corresponding to the peak; as well as In the dimension aggregation step, in each micro region, the two-dimensional axes of mass-to-charge ratio and ion mobility are aggregated into a one-dimensional axis using the correlation between the mass-to-charge ratio and the ion mobility in the analysis result data extracted in the data extraction step.

6. The imaging analysis method using ion mobility mass spectrometry according to claim 5, characterized in that: The method further comprises a variable conversion step of assigning a new variable along the one-dimensional axis to each of the extracted analysis result data, and generating information showing a correspondence relationship between the value of the variable and the original ion mobility and mass-to-charge ratio.

7. The imaging analysis method using ion mobility mass spectrometry according to claim 5, characterized in that: The method further comprises a variable conversion step of assigning a unique number to each of the extracted analysis result data and creating information showing a correspondence relationship between the unique number and the original ion mobility and mass-to-charge ratio.

8. An imaging analysis device using ion mobility mass spectrometry, characterized in that: have: A measuring unit that acquires analysis result data by performing ion mobility mass analysis on a plurality of micro-regions within a predetermined measurement region in the sample; A data extraction unit performs peak detection on the acquired analysis result data in each micro region, and extracts the analysis result data corresponding to the peak; as well as The dimensional aggregation unit aggregates the two-dimensional axes of mass-to-charge ratio and ion mobility into a one-dimensional axis for each micro region using the correlation between the mass-to-charge ratio and ion mobility in the analysis result data extracted by the data extraction unit.

9. The imaging analysis device using ion mobility mass spectrometry according to claim 8, characterized in that: The method further comprises a variable conversion unit for assigning a new variable along the one-dimensional axis to each of the extracted analysis result data, and for generating information indicating a correspondence relationship between the value of the variable and the original ion mobility and mass-to-charge ratio.

10. The imaging analysis device using ion mobility mass spectrometry according to claim 8, characterized in that: The method further comprises a variable conversion unit for assigning a unique number to each of the extracted analysis result data and creating information indicating a correspondence relationship between the unique number and the original ion mobility and mass-to-charge ratio.

Images