[go: up one dir, main page]

WO2016098247A1 - Appareil d'analyse - Google Patents

Appareil d'analyse Download PDF

Info

Publication number
WO2016098247A1
WO2016098247A1 PCT/JP2014/083707 JP2014083707W WO2016098247A1 WO 2016098247 A1 WO2016098247 A1 WO 2016098247A1 JP 2014083707 W JP2014083707 W JP 2014083707W WO 2016098247 A1 WO2016098247 A1 WO 2016098247A1
Authority
WO
WIPO (PCT)
Prior art keywords
data
measurement
measurement target
analysis
region
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2014/083707
Other languages
English (en)
Japanese (ja)
Inventor
建悟 竹下
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shimadzu Corp
Original Assignee
Shimadzu Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shimadzu Corp filed Critical Shimadzu Corp
Priority to PCT/JP2014/083707 priority Critical patent/WO2016098247A1/fr
Publication of WO2016098247A1 publication Critical patent/WO2016098247A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode

Definitions

  • the present invention relates to an analyzer, and more specifically, performs a predetermined analysis on each of a large number of measurement points in a two-dimensional region on a sample to acquire information about the sample near the measurement point, and the information thus collected
  • the present invention relates to an analyzer for examining the distribution of sample components and sample surface states in the two-dimensional region.
  • examples of the analyzer according to the present invention include an imaging mass spectrometer, a Fourier transform infrared spectrophotometry (FTIR) imaging apparatus, a Raman spectroscopic imaging apparatus, an electron beam microanalyzer, a scanning probe microscope, and the like.
  • Mass spectrometry imaging is a technique for examining the distribution of substances having a specific mass by performing mass analysis on each of a plurality of measurement points (microregions) in a two-dimensional region of a sample such as a biological tissue section. Applications for searching for drugs and biomarkers and for investigating the causes of various diseases and diseases are being promoted.
  • a mass spectrometer for performing mass spectrometry imaging is generally called an imaging mass spectrometer (see Non-Patent Document 1, etc.).
  • an imaging mass spectrometer since a microscopic observation is usually performed on an arbitrary two-dimensional region on a sample, an analysis target region is determined based on the microscopic observation image, and an imaging mass analysis of the region is executed. In this specification, it is referred to as an “imaging mass spectrometer”.
  • FIG. 6 is a schematic explanatory diagram of data obtained by the imaging mass spectrometer and imaging image display based on the data.
  • mass spectrum data in a predetermined mass-to-charge ratio m / z range is acquired at each of a large number of measurement points (micro regions) 102 set in a two-dimensional measurement target region 101 on the sample 100. Is done.
  • a time-of-flight mass analyzer (TOFMS) is usually used as a mass analyzer in order to realize high mass resolution. Therefore, the amount of data of mass spectrum data (or time-of-flight spectrum data) per measurement point is considerably larger than the amount of data of mass spectrum data obtained by, for example, a quadrupole mass spectrometer.
  • TOFMS time-of-flight mass analyzer
  • the amount of data of mass spectrum data (or time-of-flight spectrum data) per measurement point is considerably larger than the amount of data of mass spectrum data obtained by, for example, a quadrupole mass spectrometer.
  • it is necessary to narrow the interval between measurement points that is, increase the density
  • the total amount of data per sample is enormous.
  • JP 2013-40808 A International Publication No. 2014/175211
  • the rapid increase in the amount of data obtained by the imaging mass spectrometer is becoming a hindrance when the above data analysis processing is executed by a personal computer (or a higher performance workstation).
  • the volume of data obtained for one sample was several hundred MB to several GB, and at most several tens of GB.
  • the data capacity increases, and it is not uncommon for the data capacity to exceed 100 GB. For this reason, simply performing operations such as data copying and backup on a commonly used computer may cause trouble and difficulty in handling data files.
  • a heavy load is applied both in terms of hardware and software, and the calculation time may become abnormally long. In some cases, the processing is interrupted due to insufficient memory capacity during the processing.
  • Such a situation can occur not only in an imaging mass spectrometer but also in other analyzers that collect data by executing analysis at each of a large number of measurement points on a sample.
  • an analyzer for example, an FTIR imaging device that acquires an infrared absorption spectrum by Fourier transform infrared spectrophotometry at a number of measurement points on a sample, and a Raman scattering spectrum by Raman spectroscopy at a number of measurement points on a sample.
  • Spectroscopic Raman imaging apparatus electron beam microanalyzer for acquiring the spectrum showing the relationship between the energy and intensity of characteristic X-rays emitted from the sample at many measurement points on the sample, respectively, on the sample, on the sample
  • a scanning probe microscope that measures various physical properties such as surface potential and dielectric constant can be used.
  • the present invention has been made in view of the above problems, and as described above, in an analyzer that acquires spectra and signal values at each of a large number of measurement points on a sample, it is easy to handle a large volume of data obtained by measurement.
  • the main purpose is to reduce the analysis processing load on the computer and improve the efficiency of the analysis work.
  • the first aspect of the present invention which is made to solve the above-mentioned problem, is associated with the spatial position information of each measurement point by executing a predetermined analysis for each of the plurality of measurement points on the sample.
  • an analyzer that acquires analysis result information, a) an area setting unit for setting the measurement target area on the sample; b) a region dividing unit that divides the measurement target region set by the region setting unit into a plurality of small regions according to a predetermined condition; c)
  • the analysis result information respectively obtained for all measurement points in the measurement target region set by the region setting unit is associated with each of a plurality of small regions after being divided by the region dividing unit.
  • a file storage unit for storing a plurality of data files stored separately, d) When an imaging image showing the distribution of predetermined information in the measurement target region is created, necessary data is acquired from one data file stored in the file storage unit, and one based on the data is obtained.
  • An imaging image reproduction unit that repeats the process of creating an imaging image for one small region for a plurality of data files and combines the imaging images for the plurality of small regions to create a desired imaging image for the entire measurement target region; It is characterized by having.
  • the second aspect of the present invention which has been made to solve the above-mentioned problems, is associated with the spatial position information of each measurement point by executing a predetermined analysis for each of the plurality of measurement points on the sample.
  • an analyzer for acquiring spectral information indicating a relationship between a predetermined parameter and signal intensity a) an area setting unit for setting the measurement target area on the sample; b) Spectral information respectively obtained for all measurement points in the measurement target region is divided into data files corresponding to the parameter subranges obtained by dividing the range of the predetermined parameter values into a plurality of ranges, A file creation unit for storing the plurality of data files in a file storage unit; c) When creating an imaging image showing the distribution of predetermined information in the measurement target region, the necessary data is obtained from at least one data file stored in the file storage unit, and based on the data
  • An imaging image reproduction unit for creating a desired imaging image for the entire measurement target region It is characterized by having.
  • An exemplary embodiment of the analyzer according to the first and second aspects of the present invention is an imaging mass spectrometer.
  • the “analysis result information” in the analyzer according to the first aspect is mass spectrum data over a predetermined mass-to-charge ratio range.
  • the “predetermined parameter” is a mass-to-charge ratio
  • “spectrum information indicating the relationship between the predetermined parameter and signal intensity” is a mass over a predetermined mass-to-charge ratio range.
  • the “imaging image showing the distribution of predetermined information” is an imaging image showing the ion intensity distribution at a specific mass-to-charge ratio.
  • the “mass spectrum” may be a “time-of-flight spectrum” expressed by a flight time before conversion into a mass-to-charge ratio.
  • the mass spectrometer is a mass spectrometer capable of MS n analysis, such as an ion trap mass spectrometer, an ion trap time-of-flight mass spectrometer, a tandem quadrupole mass spectrometer, and a Q-TOF mass spectrometer.
  • the “mass spectrum” includes “MS n spectrum”.
  • the analyzer according to the first aspect of the present invention is not limited to the imaging mass spectrometer, and may be, for example, the above-described FTIR imaging apparatus, Raman spectroscopic imaging apparatus, electron beam microanalyzer, scanning probe microscope, or the like.
  • the analyzer which concerns on the 2nd aspect of this invention should just be what can obtain spectrum information in these analyzers.
  • the region setting unit sets a measurement target region on the sample according to, for example, an analyst's operation.
  • the region setting unit displays an optical microscopic observation image on the sample on the screen of the display unit, and the analyst designates an appropriate two-dimensional region on the display screen.
  • the designated area can be set as the measurement target area.
  • the region setting unit may automatically extract and set a specific region worthy of attention by image recognition processing under a predetermined condition for the microscopic observation image.
  • one data file is associated with each small area obtained by dividing the measurement target area set by the area setting unit as described above.
  • one data file is associated with each parameter small range obtained by dividing a range of predetermined parameter values such as a mass-to-charge ratio into a plurality of ranges.
  • the file storage unit stores a plurality of data files in which analysis result information is stored in association with the plurality of small areas.
  • an operation for creating a data file and saving it in the file storage unit one of two methods can be adopted. One of them is to acquire analysis result information by a predetermined analysis for all measurement points included in the measurement target area, and after that, the analysis result information is divided into a plurality of small areas in association with each other. This is a so-called batch processing method in which a data file is created and each of the data files is stored in a file storage unit.
  • the other one is a so-called sequential processing method in which each time analysis result information for one small area is obtained, a data file storing the analysis result information is created and stored in the file storage unit.
  • the analyzer according to the first aspect of the present invention is: A control unit that performs analysis control so as to execute a predetermined analysis on the measurement points included in each small region and acquire analysis result information for each of the small regions after being divided by the region dividing unit When, Under the control of the control unit, every time analysis result information for one small region is obtained, a file creation unit that creates one data file storing the analysis result information and saves it in the file storage unit; , It is good to set it as the structure further provided.
  • the former method requires a memory that temporarily stores analysis result information for all measurement points, whereas the latter method temporarily stores analysis result information for all measurement points in one small area. Since it is sufficient to prepare a memory for storage, the capacity of the temporary storage memory can be reduced.
  • the file creation unit performs an analysis result by a predetermined analysis with respect to all measurement points included in the measurement target region. After the information is acquired, the analysis result information is divided in correspondence with the plurality of parameter subranges, and the analysis result information included in the same parameter subrange at different measurement points is stored in the same data file.
  • a configuration may be adopted in which a file is created and the plurality of data files are stored in the file storage unit.
  • information necessary for creating an imaging image showing a distribution of predetermined information in the entire measurement target region is dispersed in a plurality of data files. Therefore, when creating such an imaging image, the imaging image reproduction unit obtains necessary data from a plurality of data files stored in the file storage unit, and creates a desired imaging image using the data. .
  • information necessary for creating a mass spectrometry imaging image at a specific mass-to-charge ratio is stored in one data file. What is necessary is just to acquire required data from a file and create an imaging image using the data.
  • any of the analyzers according to the first and second aspects of the present invention a large amount of data obtained by performing analysis on the measurement target region on the sample is divided into a plurality of pieces. Stored in a data file. Therefore, handling of the data file becomes easy. For example, even when it is desired to display a high resolution (high spatial resolution) imaging image in the analyzer according to the first aspect, a partial imaging image is created for each data file corresponding to a small area, and finally What is necessary is just to obtain the imaging image of the whole measurement object area
  • the number of divisions for dividing the measurement target region into small regions and the number of divisions for dividing a predetermined parameter value range into parameter small ranges may be values unique to the apparatus or may be set from the outside. However, the volume of data stored in one data file may be suppressed to a predetermined value or less.
  • the region dividing unit includes a plurality of the measurement target regions under a condition that the capacity of data stored in one data file is equal to or less than a predetermined value. It may be configured to be divided into small areas.
  • the first aspect and the second aspect according to the present invention can be used in combination. That is, the measurement target region is divided into a plurality of small regions according to a predetermined condition, and for each small region, the spectrum information obtained for each measurement point included in the small region is converted to a predetermined parameter value range. May be divided into small parameter ranges divided into a plurality. Thereby, the amount of data allocated to one data file can be further reduced.
  • the analyzer even if a large amount of data is obtained by performing analysis on the measurement target region on the sample, it can be divided into a plurality of data and stored in a plurality of data files. Data files can be handled easily. In addition, even if the capacity of one data file is small and it is desired to create an imaging image of the entire measurement target area, a process for reading out all the data to the temporary storage memory is not necessary, so a data analysis process is performed. The load on computer hardware and software can be reduced. As a result, it is possible to create and display high-resolution and high-resolution imaging images while using a computer with a relatively low speed and a small storage capacity that has been used by users. In addition, in the future, even if the resolution and resolution increase further and the amount of data obtained for one sample becomes even larger, it can be handled by increasing the number of data files. It is not necessary to update the hardware.
  • 1 is a schematic configuration diagram of an imaging mass spectrometer that is an embodiment of an analyzer according to the present invention.
  • 5 is a control / processing flowchart when performing measurement in the imaging mass spectrometer of the present embodiment.
  • FIG. 1 is a schematic configuration diagram of the imaging mass spectrometer of the present embodiment.
  • the imaging mass spectrometer performs mass analysis on each of a large number of two-dimensional measurement points on a sample, and a mass spectrum in a predetermined mass-to-charge ratio range for each measurement point (a “pixel” described later).
  • An imaging mass spectrometer 1 that acquires data
  • a control / processor 2 that controls the imaging mass analyzer 1 and executes various data processing on the data obtained by the imaging mass analyzer 1, and an imaging mass analyzer 1.
  • a large-capacity external storage device 4 such as a hard disk drive (HDD) or solid state drive (SSD) that stores the data acquired in 1, an operation unit 5 operated by an analyst, and a display unit that displays analysis results and the like 6.
  • HDD hard disk drive
  • SSD solid state drive
  • the imaging mass spectrometer 1 performs an optical observation of a sample placed on a movable sample stage 11 and mass analysis of a measurement point of the sample on the sample stage 11, that is, a micro region.
  • Matrix assisted laser desorption ionization (MALDI) -ion trap (IT) -mass analyzer 13 which is a time-of-flight mass spectrometer (TOFMS).
  • the mass spectrometric unit 13 irradiates a sample with laser light in an air atmosphere to ionize components in the sample.
  • the MALDI laser irradiation unit 131 collects ions generated from the sample and transports them to a vacuum atmosphere.
  • the control / processing unit 2 includes an analysis control unit 21, a measurement region setting unit 22, a region division unit 23, a division condition storage unit 24, a measurement condition storage unit 25, a data collection unit 31, a mass spectrum creation unit 32, and an optical image data storage.
  • Function blocks such as a temporary storage memory 33 in which an area 331 and a spectrum data storage area 332 are prepared, a data file creation unit 34, a low resolution file creation unit 35, a multivariate analysis processing unit 36, and an imaging image creation processing unit 37 are provided.
  • the entity of the control / processing unit 2 is a personal computer (or higher performance workstation) including a CPU, RAM, ROM, etc., and operates dedicated control / processing software installed on the computer on the computer. As a result, the functional blocks as described above are realized. Further, the external storage device 4 is provided with a data file storage area 42 and a low resolution data file storage area 41.
  • FIG. 2 is a control / processing flowchart at the time of measurement execution in the imaging mass spectrometer of the present embodiment
  • FIG. 3 is an explanatory diagram of an example of division of the measurement target region in the imaging mass spectrometer of the present embodiment.
  • a measurement object cut out from a living tissue is placed on a sample plate, and a sample 100 is prepared by applying an appropriate matrix to the surface.
  • the analyst sets the sample 100 on the sample stage 11 and performs a predetermined operation for optical observation using the operation unit 5.
  • the observation unit 12 captures an image on the sample 100
  • the control / processing unit 2 receiving the image data displays the image on the screen of the display unit 6 and also stores the image in the temporary storage memory 33. It is stored in the optical image data storage area 331.
  • the analyst designates an appropriate measurement target region on the sample 100 with the operation unit 5 with reference to the displayed image.
  • the analyst appropriately sets measurement conditions such as a mass-to-charge ratio range and spatial resolution (step S1). Of course, such measurement conditions may be defaults regardless of the analyst's settings.
  • Information indicating the set measurement conditions and the measurement target area is stored in the measurement condition storage unit 25.
  • the measurement region setting unit 22 determines whether or not the measurement target region needs to be divided based on the set measurement target region and the division condition stored in the division condition storage unit 24. Is determined (steps S2 and S3).
  • the division condition is a condition for limiting the maximum amount of data stored in one data file corresponding to one small area after division. For example, the maximum value of the number of measurement points included in one small area (For example, tens of thousands of pixels to hundreds of thousands of pixels) is a division condition. Since one measurement point corresponds to one pixel on the imaging image, in the following description, the unit of the number of measurement points is pixel.
  • This division condition may be determined as a value unique to the apparatus, or may be set by the analyst from the operation unit 5.
  • step S4 If the number of measurement points included in the set measurement target area is smaller than the maximum value of the number of measurement points defined by the division condition, it is not necessary to divide the measurement target area. In that case, it is determined No in step S3, step S4 is passed, and the process proceeds to step S5.
  • the area division unit 23 divides the measurement target area into a plurality of small areas based on the division condition (step S4). That is, the number of measurement points included in one small region may be set to be equal to or less than the maximum value of the number of measurement points determined by the division condition.
  • a maximum value of the number of measurement points may be determined in each of the biaxial directions, and mechanically divided by the position of the maximum value.
  • the size of the measurement target area is 2000 pixels in the x-axis direction and 800 pixels in the y-axis direction.
  • the division condition is that the maximum value of the number of measurement points included in one small area is 65536 pixels, and the maximum size of the small area is a rectangular shape of 256 ⁇ 256 pixels.
  • 32 small areas are set as shown in FIG. 3B.
  • consecutive numbers are assigned to the small areas, and the consecutive numbers are indicated by #n, where n is 1 to 32.
  • the small areas # 1 to # 7, # 9 to # 15, and # 17 to # 23 have a size of 256 ⁇ 256 pixels.
  • the small areas # 8, # 16, and # 24 have a size of 208 ⁇ 256 pixels.
  • the small areas # 25 to # 31 have a size of 256 ⁇ 32 pixels.
  • the small area # 32 has a size of 208 ⁇ 32 pixels.
  • FIG. 3C is an example of a display image in such a case.
  • the analysis control unit 21 starts the measurement in response to the instruction.
  • the analysis control unit 21 determines whether or not there is a division of the measurement target region (step S6). Then, when there is no division, the analysis control unit 21 operates the imaging mass analysis unit 1 and sequentially executes measurement for each measurement point in the measurement target region set on the sample 100 (step S7).
  • the sample stage 11 is moved by a drive mechanism (not shown) so that the measurement point that is the first measurement target comes to the irradiation position of the laser beam.
  • a pulsed laser beam is irradiated from the MALDI laser irradiation unit 131 to the measurement point, the components in the sample 100 existing near the irradiation site are ionized.
  • the generated ions are transferred into the vacuum atmosphere through the ion introduction part 132, converged by the ion guide 133, introduced into the ion trap 134, and temporarily held.
  • the ions held in the ion trap 134 are ejected all at a predetermined timing, introduced into the flight space in the flight tube 135, and fly through the flight space to reach the detector 136. While flying in the flight space, various ions are separated according to the mass-to-charge ratio, and reach the detector 136 in ascending order of the mass-to-charge ratio.
  • An analog detection signal from the detector 136 is converted into digital data by an analog-digital converter (not shown) and input to the data collection unit 31.
  • This data is time-of-flight spectrum data showing the relationship between ion flight time and ion intensity, and the mass spectrum creation unit 32 converts the time-of-flight into a mass-to-charge ratio, thereby converting the mass spectrum data from the time-of-flight spectrum data.
  • Ask. This mass spectrum data is stored in the spectrum data storage area 332 of the temporary storage memory 33.
  • step 1 Since the amount of ions obtained by a single laser beam irradiation is small and the variation in the amount of ions is large, a plurality of measurements are performed at the same measurement point, and the measurement is performed a plurality of times.
  • the time-of-flight spectrum data obtained in step 1 is integrated to obtain time-of-flight spectrum data for one measurement point, and a mass spectrum is obtained from this.
  • the sample stage 11 When the mass spectrum data for a certain measurement point is stored in the temporary storage memory 33 as described above, the sample stage 11 is moved so that the measurement point to be measured next comes to the laser beam irradiation position.
  • the measurement is terminated.
  • the data file creation unit 34 creates one data file in which the mass spectrum data for the entire measurement target area stored in the spectrum data storage area 332 of the temporary storage memory 33 is stored.
  • the data file is saved in the data file storage area 42 of the external storage device 4 (step S8).
  • the low-resolution file creation unit 35 may create a low-resolution data file, which will be described later.
  • step S6 If it is determined in step S6 that there is a division, the analysis control unit 21 sets the variable N to 1 (step S9), and each measurement included in the small region #N determined by the region division process in step S4. Mass analysis is performed on the point (step S10).
  • the procedure of mass spectrometry is as described above, and the only difference is that the measurement points to be measured are limited to one small region. For example, in the example of FIG. 3, since there are a maximum of 256 ⁇ 256 measurement points in one small region, mass spectrum data is obtained for each of the measurement points, and the data is stored in the spectrum of the temporary storage memory 33. It is stored in the data storage area 332.
  • the data file creation unit 34 stores the mass spectrum data for one small area stored in the spectrum data storage area 332 of the temporary storage memory 33. Is created, and this data file is stored in the data file storage area 42 of the external storage device 4 (step S11). After that, the analysis control unit 21 determines whether or not the variable N is the total number of small areas for the measurement target area, that is, the number of divisions (step S12). If the variable N has reached the total number of small areas, the process ends.
  • step S13 the process returns to step S10, and the measurement for the next unmeasured small area is executed. Therefore, by repeating steps S10 to S13, mass analysis is performed on measurement points included in all the small regions obtained by dividing the measurement target region, and the obtained mass spectrum data is obtained for each small region.
  • the data files are stored in the data file storage area 42 of the external storage device 4 as different data files.
  • one data file stored in the external storage device 4 includes a header area and a data area, and the header area is a data file corresponding to one measurement target area.
  • File division information such as information indicating information indicating which position in a measurement target region is a small region is stored.
  • the measurement target region designated by the analyst when the measurement target region designated by the analyst is wide and the amount of data obtained from the measurement target region increases, the measurement target region includes a plurality of small measurement target regions. It is automatically divided into areas, and an independent data file is created for each small area.
  • the measurement target region designated by the analyst when the measurement target region designated by the analyst is narrow and the amount of data obtained from the measurement target region is small, one data file for the entire measurement target region is created as in the prior art.
  • a process for displaying an imaging image for a measurement target area in a state where a plurality of data files for one measurement target area is stored in the external storage device 4 as described above will be described.
  • the imaging image creation processing unit 37 accesses the data file corresponding to one small area included in the measurement target area, which is stored in the data file storage area 42 of the external storage device 4, and the small file.
  • the resolution (spatial resolution) of the imaging image is high, this corresponds to a part of the measurement target region.
  • an imaging image for one small region is obtained, it is displayed on the screen of the display unit 6 in order, so that the imaging image is displayed. It is possible to reduce the waiting time when no display is performed.
  • the imaging mass spectrometer of the present embodiment when the measurement target area specified by the analyst is wide and the amount of data to be obtained is enormous, data for each small area obtained by dividing the measurement target area into a plurality of areas. Mass spectral data can be saved in separate files. As a result, handling of the data file becomes easy, and the load on the hardware and software when handling the data file is reduced.
  • the imaging mass spectrometer of the present embodiment also includes a low-resolution data file mainly used for multivariate analysis in addition to a normal data file capable of creating a high-definition image. It is prepared so that it can be saved in the low resolution data file storage area 41 of the external storage device 4.
  • step S8 when creating one data file in which mass spectrum data for the entire measurement target region is stored, the low resolution file creation unit 35 concurrently or after the creation of the data file is completed.
  • Reduce the amount of data Specifically, for example, the number of measurement points is reduced by appropriately thinning out the measurement points, data points in the mass-to-charge ratio direction at each measurement point are down-sampled, and the number of bits of signal intensity value data is reduced.
  • One or more methods can be used. More preferably, instead of simply thinning out the measurement points, the amount of data may be reduced by performing a binning process on data obtained at adjacent measurement points. Such processing corresponds to processing for creating a thumbnail image for a high-definition imaging image.
  • the data file whose data amount is greatly reduced is stored in the low resolution data file storage area 41 of the external storage device 4.
  • a data file is created that significantly reduces the amount of mass spectral data for the entire measurement target area.
  • the data is stored in the low resolution data file storage area 41 of the external storage device 4.
  • the multivariate analysis processing unit 36 When performing multivariate analysis processing for the purpose of searching for a characteristic mass-to-charge ratio in the measurement target region, the multivariate analysis processing unit 36 stores the low-resolution data file in the external storage device 4. Data is read from the area 41, and a predetermined multivariate analysis process using the data, for example, principal component analysis is performed. Although the resolution and resolution of the data used at this time are low, there is usually no problem in grasping the distribution tendency in the entire measurement target region by the multivariate analysis processing. Alternatively, the multivariate analysis may be performed using only the main region among the divided measurement target regions.
  • the mass-to-charge ratio is handled from the data file stored in the data file storage area 42 of the external storage device 4.
  • the data to be read may be read out and a high-definition imaging image may be created and displayed based on the data.
  • the size of the data file to be handled can be reduced, and the hardware load can be reduced.
  • FIG. 4 is an explanatory diagram of another example of division of the measurement target region.
  • a plurality of measurement points at positions separated by L measurement point intervals in the x-axis and y-axis directions in the measurement target region 101 are obtained as a group for the measurement points.
  • Mass spectrum data is stored in the same data file.
  • the measurement points from which the mass spectrum data stored in the same data file are not necessarily adjacent or close to each other on the sample.
  • the measurement target area is divided as shown in FIG. 4, when an imaging image having a specific mass-to-charge ratio is created using data read from one data file stored in the external storage device 4, the measurement target area is Rather than a part of the high-resolution image, a rough, that is, low-resolution image of the entire measurement target area is obtained.
  • the creation and connection of imaging images based on data from a plurality of data files are sequentially advanced, the resolution of the imaging image with respect to the entire measurement target region gradually increases. Therefore, by displaying such an imaging image on the screen of the display unit 6, when an analyst sees an imaging image with a low resolution and recognizes that the image is not a desired image, the processing is stopped even during the imaging image creation process. be able to.
  • the measurement target area is divided into a plurality of small areas, and the data files are respectively divided.
  • the data amount stored in one data file is within a predetermined amount.
  • data division in the mass-to-charge ratio direction may be performed instead of spatial division.
  • FIG. 5 is an explanatory diagram of an example of data division in an imaging mass spectrometer of another embodiment.
  • the mass spectrum data is divided into n pieces in the mass-to-charge ratio direction, and the mass spectrum data obtained for all measurement points in the measurement target region is divided into n pieces, and the same mass charge is obtained at different measurement points.
  • the data included in the ratio range in the same data file all the data is stored in n data files in total. In this case, for example, if it is desired to create an imaging image for the mass-to-charge ratio included in the mass-to-charge ratio range of M 3 , it is only necessary to read data from only the data file of # 3. There is no need to read data across.
  • this invention applies not only to an imaging mass spectrometer but to each of many measurement points set in the measurement object area
  • the present invention can be applied to various analyzers that acquire some spectrum information and signal values.
  • the FTIR imaging apparatus Fourier transform infrared spectrophotometry is performed on a large number of measurement points in a measurement target region on a sample, and infrared absorption spectra are respectively acquired.
  • Raman spectroscopic imaging apparatus Raman spectroscopic measurement is performed on a large number of measurement points in the measurement target region on the sample, and a Raman scattering spectrum is acquired.
  • the electron beam microanalyzer an electron beam is irradiated as an excitation beam to each of a large number of measurement points in a measurement target region on the sample, thereby showing the relationship between the energy and intensity of characteristic X-rays emitted from the sample. Acquire each spectrum.
  • an atomic force microscope such as a scanning probe microscope measures various physical properties such as surface potential and dielectric constant in addition to sample height information at a large number of measurement points in a measurement target region on the sample. Therefore, in these analyzers, similarly to the imaging mass spectrometer described above, if the measurement target area is divided into a plurality of small areas, and data files for storing data are divided into the small areas, the data files are handled. It becomes easy.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Electrochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

Lorsqu'une région cible de mesure sur un échantillon est établie (S1), la nécessité de diviser la région cible de mesure est déterminée en fonction de conditions de division, telles que la taille maximale des données d'un fichier (S2-S3). Si la région cible de mesure est grande et doit être divisée, la région cible de mesure est divisée en une pluralité de petites régions (S4) selon les conditions de division. Lorsque la mesure a commencé, dans chaque petite région, l'analyse de masse est effectuée séquentiellement au niveau de points de mesure inclus dans cette petite région (S10). Une fois que la mesure au niveau d'une petite région est terminée, un fichier de données dans lequel sont stockées ces données de mesure est créé et est sauvegardé dans un dispositif de stockage externe (S11). En répétant cette opération pour toutes les petites régions, le même nombre de fichiers de données que le nombre de petites régions est sauvegardé dans le dispositif de stockage externe. Lors de la création d'une image d'imagerie, les données requises dans chaque fichier de données sont lues, une image d'imagerie correspondant à la petite région est créée, et par l'assemblage de l'une de leurs pluralités, une image d'imagerie pour la totalité de la région cible de mesure est créée. En conséquence, la taille des fichiers de données diminue, ce qui permet de faciliter la manipulation de fichiers et également de réduire la charge sur le matériel et autre.
PCT/JP2014/083707 2014-12-19 2014-12-19 Appareil d'analyse Ceased WO2016098247A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/JP2014/083707 WO2016098247A1 (fr) 2014-12-19 2014-12-19 Appareil d'analyse

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2014/083707 WO2016098247A1 (fr) 2014-12-19 2014-12-19 Appareil d'analyse

Publications (1)

Publication Number Publication Date
WO2016098247A1 true WO2016098247A1 (fr) 2016-06-23

Family

ID=56126165

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2014/083707 Ceased WO2016098247A1 (fr) 2014-12-19 2014-12-19 Appareil d'analyse

Country Status (1)

Country Link
WO (1) WO2016098247A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020094854A (ja) * 2018-12-11 2020-06-18 株式会社島津製作所 イメージング分析装置
CN114096839A (zh) * 2019-08-01 2022-02-25 株式会社岛津制作所 成像质量分析装置
CN116047114A (zh) * 2023-01-05 2023-05-02 北京量子信息科学研究院 表面离子阱囚禁电场分布的测量方法及测量装置

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001519944A (ja) * 1997-03-03 2001-10-23 バクス リサーチ ラボラトリーズ インコーポレイテッド コンピュータ制御の顕微鏡から試料の拡大イメージを取得し再構成するための方法および装置
JP2006519443A (ja) * 2003-02-28 2006-08-24 アペリオ・テクノロジーズ・インコーポレイテッド バーチャルスライドを閲覧するためのシステムおよび方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001519944A (ja) * 1997-03-03 2001-10-23 バクス リサーチ ラボラトリーズ インコーポレイテッド コンピュータ制御の顕微鏡から試料の拡大イメージを取得し再構成するための方法および装置
JP2006519443A (ja) * 2003-02-28 2006-08-24 アペリオ・テクノロジーズ・インコーポレイテッド バーチャルスライドを閲覧するためのシステムおよび方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CLERENS,S. ET AL.: "CreateTarget and Analyze This!: new software assisting imaging mass spectrometry on Bruker Reflex IV and Ultraflex II instruments", RAPID COMMUNICATIONS IN MASS SPECTROMETRY, vol. 20, no. Issue 20, pages 3061 - 3066 *
ROBICHAUD,G. ET AL.: "MSiReader: An Open-Source Interface to View and Analyze High Resolving Power MS Imaging Files on Matlab Platform", JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, vol. 24, no. Issue 5, 28 March 2013 (2013-03-28), pages 718 - 721, XP035354301, DOI: doi:10.1007/s13361-013-0607-z *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020094854A (ja) * 2018-12-11 2020-06-18 株式会社島津製作所 イメージング分析装置
CN111307920A (zh) * 2018-12-11 2020-06-19 株式会社岛津制作所 成像分析装置
JP7172537B2 (ja) 2018-12-11 2022-11-16 株式会社島津製作所 イメージング分析装置
CN111307920B (zh) * 2018-12-11 2023-04-07 株式会社岛津制作所 成像分析装置
CN114096839A (zh) * 2019-08-01 2022-02-25 株式会社岛津制作所 成像质量分析装置
CN116047114A (zh) * 2023-01-05 2023-05-02 北京量子信息科学研究院 表面离子阱囚禁电场分布的测量方法及测量装置

Similar Documents

Publication Publication Date Title
JP6699735B2 (ja) イメージング質量分析装置
JP4973360B2 (ja) 質量分析装置
JP6465121B2 (ja) 分析データ処理方法及び装置
JP5950034B2 (ja) イメージング質量分析データ処理方法及びイメージング質量分析装置
JP6569805B2 (ja) イメージング質量分析装置
JP6597909B2 (ja) 質量分析データ処理装置
JP5454409B2 (ja) 質量分析装置
WO2016098247A1 (fr) Appareil d'analyse
JP7004073B2 (ja) イメージングデータ処理装置
CN112204388B (zh) 谱数据处理装置以及分析装置
JP7001157B2 (ja) イメージング質量分析データ処理装置
CN113049670B (zh) 成像分析数据处理方法以及成像分析数据处理装置
JP7248126B2 (ja) イメージング質量分析装置
JP7622864B2 (ja) 質量分析データ解析方法及びイメージング質量分析装置
JP7582493B2 (ja) 質量分析データ解析方法及びイメージング質量分析装置
WO2021095210A1 (fr) Dispositif d'analyse d'imagerie et procédé d'interprétation des données d'imagerie

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14908457

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14908457

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP