IMAGING MASS SPECTROMETRY DATA PROCESSING DEVICE

Abstract

After collecting mass spectrometry data for each of a large number of measurement points in the two-dimensional region on the sample with the imaging mass spectrometry unit, the user inputs the target compound whose two-dimensional distribution is desired to be observed from the input unit. The image display instruction reception unit obtains the m/z range for data integration from the precise m/z value and the allowable width of m/z for each target compound. The mass-to-charge ratio range overlap determination unit determines the presence or absence of overlap between the m/z ranges of a plurality of compounds, and if there is an overlap, the overlap determination result processing unit creates and displays on the screen of the display unit a list of compounds whose m/z ranges overlap, for example. This urges the user to review the compounds and allowable values.

Claims

1. An imaging mass spectrometry data processing device configured to process mass spectrometry data obtained from each of a plurality of micro regions within a two-dimensional region on a sample, the imaging mass spectrometry data processing device comprising: a) an input setting unit configured to allow a user to designate a compound or compounds or a mass-to-charge ratio value whose two-dimensional intensity distribution based on the mass spectrometry data is to be observed; b) a determination unit configured to determine, when there are a plurality of mass-to-charge ratio values corresponding to a compound or compounds designated by the user via the input setting unit and/or when there are a plurality of mass-to-charge ratio values designated by a user via the input setting unit, whether there is an overlap between a plurality of mass-to-charge ratio ranges having a predetermined or designated allowable width for each of the plurality of mass-to-charge ratio values; and c) an information provision unit configured to provide, when the determination unit determines that there is an overlap between a plurality of mass-to-charge ratio ranges, the user with information that mass-to-charge ratio ranges overlap in a compound or compounds or a mass-to-charge ratio value designated by a user.

2. The imaging mass spectrometry data processing device according to claim 1, wherein the information provision unit issues a warning in a mode recognizable by a user.

3. The imaging mass spectrometry data processing device according to claim 1, wherein the information provision unit lists and displays on a screen of a display unit compounds and/or mass-to-charge ratio values whose mass-to-charge ratio ranges overlap.

4. The imaging mass spectrometry data processing device according to claim 1, further comprising an image creation unit configured to create an image showing a two-dimensional intensity distribution using the mass spectrometry data for each of the plurality of mass-to-charge ratio ranges based on designation by a user via the input setting unit, and wherein when displaying image information created by the image creation unit on a screen of a display unit, the information provision unit displays an image corresponding to compounds and/or mass-to-charge ratio values whose mass-to-charge ratio ranges overlap in a manner visually distinguishable from another image.

5. The imaging mass spectrometry data processing device according to claim 1, further comprising, when the determination unit determines that there is an overlap between a plurality of mass-to-charge ratio ranges, a mass-to-charge ratio range change unit configured to change at least one mass-to-charge ratio range among a plurality of overlapping mass-to-charge ratio ranges in order to eliminate the overlap.

6. The imaging mass spectrometry data processing device according to claim 1, wherein when the determination unit determines that a plurality of mass-to-charge ratio ranges overlap, the imaging mass spectrometry data processing device merges a plurality of overlapping mass-to-charge ratio ranges, and treats a plurality of compounds and/or mass-to-charge ratio values corresponding to the plurality of mass-to-charge ratio ranges as one constructive component.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0034] FIG. 1 is a schematic configuration diagram of an embodiment of an imaging mass spectrometer including an imaging mass spectrometry data processing device according to the present invention.

[0035] FIGS. 2A-2D are explanatory diagrams of an MS image creation operation in the imaging mass spectrometer of the present embodiment.

[0036] FIGS. 3A-3B are a schematic diagram showing the relationship between mass-to-charge ratio ranges when calculating signal strength values of a plurality of compounds adjacent to each other on the m/z axis.

[0037] FIG. 4 is a diagram showing an example of a list displaying a plurality of compounds whose mass-to-charge ratio ranges overlap.

[0038] FIG. 5 is a diagram showing an example of a display screen for displaying MS images of a plurality of compounds whose mass-to-charge ratio ranges overlap.

[0039] FIGS. 6A-6B are schematic diagrams for illustrating the operation when changing the mass-to-charge ratio ranges corresponding to a plurality of compounds adjacent to each other on the m/z axis.

[0040] FIGS. 7A-7B are schematic diagrams for illustrating the operation when merging the mass-to-charge ratio ranges corresponding to a plurality of compounds adjacent to each other on the m/z axis.

DESCRIPTION OF EMBODIMENTS

[0041] Hereinafter, an embodiment of an imaging mass spectrometer including the imaging mass spectrometry data processing device according to the present invention will be described with reference to the accompanying drawings.

[0042] FIG. 1 is a schematic configuration diagram of an imaging mass spectrometer according to the present embodiment, and FIGS. 2A-2D are explanatory diagrams of an MS image creation operation in the imaging mass spectrometer of the present embodiment.

[0043] The imaging mass spectrometer of the present embodiment includes an imaging mass spectrometry unit 1 that performs measurement on a sample, a data processing unit 2, and an input unit 3 and a display unit 4 being user interfaces. It should be noted that although not described here, the imaging mass spectrometer also includes an optical microscope image acquiring unit that captures an optical microscope image on the sample.

[0044] The imaging mass spectrometry unit 1 includes, for example, a matrix-assisted laser desorption/ionization ion trap time-of-flight mass spectrometer, and as shown in FIG. 2A, performs mass spectrometry on each of the large number of measurement points (micro regions) 102 in the two-dimensional measurement region 101 on the sample 100 such as a biological tissue section to acquire mass spectrometry data for each measurement point. Here, the mass spectrometry data is mass spectrum data over a predetermined mass-to-charge ratio range, but may be MS.sup.n spectrum data for a specific precursor ion.

[0045] The data processing unit 2 receives the mass spectrum data at each measurement point collected by the imaging mass spectrometry unit 1 to perform predetermined processing, and includes functional blocks such as a data collection unit 20, a data storage unit 21, an image display instruction reception unit 22, a mass-to-charge ratio range overlap determination unit 23, an overlap determination result processing unit 24, a mass-to-charge ratio range change processing unit 25, an image creation unit 26, and a display processing unit 27.

[0046] Generally, the substance of the data processing unit 2 is a personal computer (or a higher-performance workstation), and causing the dedicated software installed on the computer to operate on the computer achieves the function of each block described above. In that case, the input unit 3 is a pointing device such as a keyboard or a mouse, and the display unit 4 is a display monitor.

[0047] In the imaging mass spectrometer of the present embodiment, when the user (operator) sets the sample 100 at a predetermined measurement position of the imaging mass spectrometry unit 1 and performs a predetermined operation on the input unit 3, an optical microscopic image acquiring unit (not shown) photographs the surface of the sample 100 and displays the image on the screen of the display unit 4. The user designates the desired measurement region 101 on the image with the input unit 3, and then instructs the start of measurement. Then, the imaging mass spectrometry unit 1 executes mass spectrometry on each of a large number of measurement points 102 in the measurement region 101 as shown in FIG. 2A, and acquires mass spectrum data over a predetermined mass-to-charge ratio range. At this time, the data collection unit 20 executes what is called profile acquisition, and collects profile spectrum data being a continuous waveform in the mass-to-charge ratio direction over a predetermined mass-to-charge ratio range as shown in FIG. 2B to store the profile spectrum data in the data storage unit 21. As a matter of course, what is stored in the data storage unit 21 is a string of digitized data on samples of continuous profile waveforms sampled at a predetermined sampling interval (sufficiently smaller than the peak width of the waveform).

[0048] After the measurement of the target sample 100 is completed, the user designates the compound whose two-dimensional intensity distribution is desired to be checked (hereinafter referred to as target compound) in the sample 100 from the input unit 3. Designation of the target compound can be made by a method such as inputting the compound name directly, or selecting a compound from a list of compounds prepared in advance. In addition, when a plurality of target compounds are designated, the target compounds may be designated one by one by the above method, but listing a plurality of target compounds in advance and selecting the list may make it possible to collectively designate the plurality of target compounds on the list.

[0049] Instead of designating the target compound, it is also possible to designate the mass-to-charge ratio value (hereinafter referred to as target mass-to-charge ratio value) itself whose two-dimensional intensity distribution is desired to be checked. For example, the user has only to be able to perform designation by selecting an appropriate peak with a mass-to-charge ratio from the peak list created by performing peak detection on the mass spectrum obtained in the sample. Naturally, the user may be able to directly input the mass-to-charge ratio value. It should be noted that when the target mass-to-charge ratio value is designated, the compound corresponding to the mass-to-charge ratio may be unknown.

[0050] Together with designating the target compound and the target mass-to-charge ratio value as the checking target of the two-dimensional intensity distribution, the user designates the allowable width M at the time of calculating the signal strength value. However, when a plurality of target compounds and target mass-to-charge ratio values are designated, the allowable width does not necessarily have to be designated for each target compound and each target mass-to-charge ratio value, and for example, the allowable width may be common to all target compounds and target mass-to-charge ratio values. In addition, the allowable width does not have to be designated with the numerical value of the unit of the mass-to-charge ratio such as Da and u, and may be designated with the ratio to the central mass-to-charge ratio value, such as ppm. Naturally, other designation methods may be used. What is important is that allowable width of some kind is set for each target compound or each target mass-to-charge ratio.

[0051] When the target compound is designated, the image display instruction reception unit 22 refers to the compound database stored in advance or the like, and obtains the precise mass-to-charge ratio value corresponding to the designated compound (normally the theoretical value of the mass-to-charge ratio). Therefore, even when any one of the target compound and the target mass-to-charge ratio value is designated, information on the central mass-to-charge ratio value M and the allowable width M can be obtained for each target compound or for each target mass-to-charge ratio value.

[0052] The mass-to-charge ratio range overlap determination unit 23 calculates the mass-to-charge ratio range [MM to M+M] for integrating the signal strength value from the mass-to-charge ratio value M and the allowable width M for each target compound or each target mass-to-charge ratio value. Then, it is examined whether the mass-to-charge ratio range of all the designated target compounds and the mass-to-charge ratio range of the target mass-to-charge ratio values overlap.

[0053] FIG. 3A is an example when there is no overlap between the mass-to-charge ratio range [MaM to Ma+M] of a compound A and the mass-to-charge ratio range [MbM to Mb+M] of a compound B, which are adjacent to each other on the mass-to-charge ratio axis. On the other hand, FIG. 3B is an example when there is an overlap between the mass-to-charge ratio range [MaM to Ma+M] of a compound A and the mass-to-charge ratio range [MbM to Mb+M] of a compound B, which are adjacent to each other on the mass-to-charge ratio axis, and the shaded part in the drawing overlaps. The mass-to-charge ratio range overlap determination unit 23 determines the presence or absence of overlap for the entire mass-to-charge ratio range. Naturally, in some cases, the mass-to-charge ratio ranges of three or more compounds may overlap.

[0054] When there is no overlap between the mass-to-charge ratio ranges, the image creation unit 26 notified of the result extracts data included in the mass-to-charge ratio range of the target compound and the target mass-to-charge ratio value in the profile spectrum data of each measurement point 102 to read the data from the data storage unit 21, and obtains the signal strength value by integrating the data included in the mass-to-charge ratio range (see FIG. 2C). Thus, since the signal strength values of each of the large number of measurement points 102 included in the measurement region 101 can be obtained for each target compound or each target mass-to-charge ratio value, arranging the signal strength value two-dimensionally according to the position of the measurement point and giving the display color to the signal strength value according to a predetermined color scale creates a heat map-shaped mass spectrometry image 200 as shown in FIG. 2D. The display processing unit 27 displays the mass spectrometry image 200 created for each of the target compound and the target mass-to-charge ratio value on the screen of the display unit 4 in the form of, for example, a list.

[0055] On the other hand, when at least one set of a plurality of mass-to-charge ratio ranges has overlap, the overlap determination result processing unit 24 notified of the result executes any one or a plurality of the following pieces of processing at the same time. It should be noted that the user can preferably set in advance what kind of processing is to be executed.

<First Processing> Warning of Overlap of Mass-To-Charge Ratio Ranges

[0056] The overlap determination result processing unit 24 displays a warning display on the screen of the display unit 4 indicating that there is an overlap between the mass-to-charge ratio ranges. It should be noted that at the same time, a warning sound or the like may be emitted.

<Second Processing> List Display of Compounds or the Like whose Mass-To-Charge Ratio Ranges Overlap

[0057] The overlap determination result processing unit 24 creates a list of target compounds or target mass-to-charge ratio values whose mass-to-charge ratio ranges overlap, and displays the list on the screen of the display unit 4. FIG. 4 is an example of a list when the mass-to-charge ratio ranges of compounds A and B overlap as shown in FIG. 3B. From the displayed list, the user can immediately check, for example, which compound and which compound have the mass-to-charge ratio range overlapping.

[0058] In the case of the above first processing and second processing, warnings and lists are displayed, and while leaving the mass-to-charge ratio ranges in a state of having overlap, a mass spectrometry image may be created for each target compound or for each mass-to-charge ratio value as described above, or after automatically changing the mass-to-charge ratio range as described below, a mass spectrometry image may be created for each target compound or for each mass-to-charge ratio value as described above. Alternatively, after warning and lists are displayed, an instruction from the user is awaited, that is, a mass spectrometry image is not immediately created and if it is instructed to create an image by the user, and then a mass spectrometry image may be created.

<Third Processing> Explicit Representation of Overlapping Compounds or the Like on Mass Spectrometry Image Display

[0059] In response to the instruction of the overlap determination result processing unit 24, the image creation unit 26 creates a mass spectrometry image for each target compound or for each mass-to-charge ratio value as described above while leaving the mass-to-charge ratio ranges in a state of partial overlap. The display processing unit 27 displays the mass spectrometry image created for each of the target compound and the target mass-to-charge ratio value on the screen of the display unit 4 in the form of, for example, a list. At this time, the overlap determination result processing unit 24 denotes a mark or the like such that the mass spectrometry image corresponding to the target compounds or the target mass-to-charge ratio values whose mass-to-charge ratio ranges overlap is distinguishable from another mass spectrometry image (that is, there is no overlap between the mass-to-charge ratio ranges) on the display.

[0060] FIG. 5 is a diagram showing an example of a mass spectrometry image list when the mass-to-charge ratio ranges of compounds A and B overlap as shown in FIG. 3B. In this example, thumbnail images of mass spectrometry images of a plurality of target compounds designated by the user are arranged side by side in the image list screen 400. Among them, the mass spectrometry images of compounds A and B whose mass-to-charge ratio ranges overlap are surrounded by a frame 401 of the same display color. Thus, the user can recognize at a glance the mass spectrometry images of the target compounds and target mass-to-charge ratio values, whose mass-to-charge ratio ranges overlap. Naturally, instead of the frame 401 as shown in FIG. 5, marks and symbols having any shape such as arrows can be used. In addition, the images may be appropriately rearranged and displayed so that the mass spectrometry images of the target compounds and target mass-to-charge ratio values, whose mass-to-charge ratio ranges overlap, fall within the same frame. In any case, the mass spectrometry images of the target compounds and target mass-to-charge ratio values whose mass-to-charge ratio ranges overlap have only to be displayed in such a manner that they can be easily distinguished from other images.

[0061] As described above, when a mass spectrometry image is created in a state of the mass-to-charge ratio ranges of compounds A and B overlapping, the signal strength value of the part where the mass-to-charge ratio ranges overlap is doubly reflected in both the mass spectrometry image of the compound A and the mass spectrometry image of the compound B. Actually, the signal strength value of the overlapping portion is the signal strength value of any one of the compounds A and B, or should be distributed to both compounds A and B at an appropriate ratio. Therefore, in any case, the accuracy of the two-dimensional intensity distribution of the mass spectrometry image is lowered. Thus, in order to create a more accurate mass spectrometry image, it is necessary for the user to manually change the allowable width, for example, so that the mass-to-charge ratio ranges do not overlap. However, if mass spectrometry images of a large number of compounds are desired to be observed at once, the number of compounds with overlapping mass-to-charge ratio ranges also increases, and it is troublesome to manually eliminate the overlap of the mass-to-charge ratio ranges one by one.

[0062] In the device of the present embodiment, when the user performs a predetermined operation from the input unit 3, the mass-to-charge ratio range change processing unit 25 implements processing of automatically changing the mass-to-charge ratio range so that the overlap of the mass-to-charge ratio ranges is eliminated. FIGS. 6A-6B are schematic diagrams for illustrating the operation when changing the mass-to-charge ratio ranges corresponding to a plurality of compounds adjacent to each other on the m/z axis, and FIGS. 7A-7B are schematic diagrams for illustrating the operation when merging the mass-to-charge ratio ranges corresponding to a plurality of compounds adjacent to each other on the m/z axis.

[0063] The mass-to-charge ratio range change processing unit 25 first obtains the width of the overlap when an execution of processing for eliminating the overlap between the mass-to-charge ratio ranges of the two compounds A and B is instructed. Then, it is determined whether the overlapping width is not less than a predetermined value smaller than the allowable width M. If the overlapping width is less than a predetermined value, as shown in FIGS. 6A-6B, the overlapping portion is divided and distributed to both sides of the divided point to reduce the allowable width. In the example in FIG. 6B, the mass-to-charge ratio range is changed by reducing the respective allowable widths on both sides of the overlapping portion by .

[0064] Ideally, since the peak shape of the profile spectrum is also a Gaussian distribution shape, the peak shape is bilaterally symmetrical. Therefore, the allowable width of each target compound may be set to M. In addition, when the allowable widths on both sides of the overlapping portion are different, it is preferable to change the distribution to both sides according to the ratio of the allowable widths.

[0065] In this way, after changing the mass-to-charge ratio range so that there is no overlap, integrating the data included in the mass-to-charge ratio range for each measurement point as described above obtains the signal strength value and creates a mass spectrometry image. Thus, it is possible to obtain a more accurate mass spectrometry image that reduces the influence of the overlap of the mass-to-charge ratio range.

[0066] On the other hand, when the overlapping width of the mass-to-charge ratio range is not less than a predetermined value smaller than the allowable width M, narrowing the mass-to-charge ratio range so as to eliminate the overlap reduces the signal strength value being the result of integration, which is disadvantageous in sensitivity. In addition, as shown in FIG. 7A, when the overlap is large, it is practically impossible to separate them. In that case, as shown in FIG. 7B, the overlapping mass-to-charge ratio ranges are merged and treated as the mass-to-charge ratio range of the mixture of the compound A and compound B.

[0067] In this way, after merging and enlarging the mass-to-charge ratio range, integrating the data included in the mass-to-charge ratio range for each measurement point as described above obtains the signal strength value and creates a mass spectrometry image. Thus, a mass spectrometry image showing a two-dimensional intensity distribution of a mixture of the compound A and the compound B can be obtained. In this case, the individual two-dimensional intensity distribution of each of compound A and compound B is not known, but the two-dimensional intensity distribution of a mixture of the two compounds can be accurately obtained.

[0068] It should be noted that the above embodiment is an example of the present invention, and even if appropriate changes, amendments, and additions are made within the scope of the gist of the present invention, it is natural that those are included in the claims of the present application.

REFERENCE SIGNS LIST

[0069] 1 . . . Imaging Mass Spectrometry Unit

[0070] 2 . . . Data Processing Unit

[0071] 20 . . . Data Collection Unit

[0072] 21 . . . Data Storage Unit

[0073] 22 . . . Image Display Instruction Reception Unit

[0074] 23 . . . Mass-To-Charge Ratio Range Overlap Determination Unit

[0075] 24 . . . Overlap Determination Result Processing Unit

[0076] 25 . . . Mass-To-Charge Ratio Range Change Processing Unit

[0077] 26 . . . Image Creation Unit

[0078] 27 . . . Display Processing Unit

[0079] 3 . . . Input Unit

[0080] 4 . . . Display Unit

[0081] 100 . . . Sample

[0082] 101 . . . Measurement Region

[0083] 102 . . . Measurement Point

[0084] 200 . . . Mass Spectrometry Image

[0085] 400 . . . Image List Screen

[0086] 401 . . . Frame