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US-12626896-B2 - Mass spectrometry data analysis method and imaging mass spectrometer

US12626896B2US 12626896 B2US12626896 B2US 12626896B2US-12626896-B2

Abstract

An imaging mass spectrometer according to the present invention includes: a measurement unit to acquire data by performing mass spectrometry on each of a plurality of micro regions in a measurement region on a sample; a narrowing unit to perform a process of narrowing a peak width with respect to each peak detected in each of a plurality of profile spectra based on the data individually obtained in the plurality of micro regions to be averaged or summed; a spectrum calculation unit to obtain an overall mass spectrum by averaging or summing the plurality of mass spectra processed by the narrowing unit; a peak selection reception unit to display the overall mass spectrum and receive an instruction from a user to select a peak on the mass spectrum; and an image creation unit to create a mass spectrometry image corresponding to the peak received by the peak selection reception unit.

Inventors

  • Shinichi Yamaguchi

Assignees

  • SHIMADZU CORPORATION

Dates

Publication Date
20260512
Application Date
20210906

Claims (6)

  1. 1 . A mass spectrometry data analysis method of analyzing data obtained by performing mass spectrometry on each of a plurality of micro regions in a measurement region on a sample, the mass spectrometry data analysis method comprising: a narrowing step of performing a process of narrowing a peak width with respect to each peak detected in each of a plurality of profile spectra individually obtained in the plurality of micro regions to be averaged or summed; a spectrum calculation step of obtaining an overall mass spectrum by averaging or summing the plurality of profile spectra subjected to the narrowing; a peak selection reception step of displaying the overall mass spectrum and receiving an instruction from a user to select a peak on the mass spectrum; and an image creation step of creating a mass spectrometry image corresponding to the peak selected in the instruction.
  2. 2 . The mass spectrometry data analysis method according to claim 1 , wherein the narrowing step includes centroiding the peak detected in the profile spectrum.
  3. 3 . The mass spectrometry data analysis method according to claim 2 , wherein the narrowing step includes performing a process of widening a width of the peak obtained by centroiding.
  4. 4 . The mass spectrometry data analysis method according to claim 2 , wherein the spectrum calculation step includes obtaining the overall mass spectrum from a discrete spectrum obtained by binning the peak obtained by centroiding according to a mass-to-charge ratio of the peak in all the plurality of micro regions to be averaged or summed, and aggregating an intensity of the peak assigned to each bin.
  5. 5 . The mass spectrometry data analysis method according to claim 1 , wherein the data is data obtained by time-of-flight mass spectrometry or Fourier transform mass spectrometry.
  6. 6 . An imaging mass spectrometer comprising: a measurement unit configured to acquire data by performing mass spectrometry on each of a plurality of micro regions in a measurement region on a sample; a narrowing unit configured to perform a process of narrowing a peak width with respect to each peak detected in each of a plurality of profile spectra based on the data individually obtained in the plurality of micro regions to be averaged or summed; a spectrum calculation unit configured to obtain an overall mass spectrum by averaging or summing the plurality of profile spectra processed by the narrowing unit; a peak selection reception unit configured to display the overall mass spectrum and receive an instruction from a user to select a peak on the mass spectrum; and an image creation unit configured to create a mass spectrometry image corresponding to the peak received by the peak selection reception unit.

Description

TECHNICAL FIELD The present invention relates to an imaging mass spectrometer and a method for analyzing data collected by the imaging mass spectrometer. BACKGROUND ART An imaging mass spectrometer is a device capable of visualizing a compound distribution on a sample such as a section of biological tissue. An imaging mass spectrometer disclosed in Patent Literature 1 is equipped with an ion source by a matrix assisted laser desorption/ionization (MALDI) method. The imaging mass spectrometer collects mass spectrum data over a predetermined mass-to-charge ratio (customarily referred to as “mass-to-charge ratio” or simply referred to as “m/z” in this specification although it is technically “m/z” in italics) range for each of micro regions created by finely segmenting a two-dimensional measurement region on a sample. Another method of imaging mass spectrometryis is also known in which mass spectrum data is acquired for each micro region by cutting out a sample piece from each micro region in a measurement region by use of a sampling method called laser microdissection, and a liquid sample prepared from each sample piece is analyzed in a mass spectrometer (see Patent Literature 2). Here, a device using such a sampling method is also included in the “imaging mass spectrometer”. In any case, the imaging mass spectrometer can obtain an image showing a distribution of, for example, a specific compound by extracting a signal intensity value at an m/z value of an ion derived from the specific compound, from mass spectrum data obtained for each micro region on a sample, and creating an image in which the signal intensity value is disposed according to a two-dimensional position of each micro region on the sample. Hereinafter, this image is referred to as mass spectrometry (MS) image. In a typical imaging mass spectrometer, in a case in which a compound to be observed, that is, a target compound is already determined, a user specifies an m/z value corresponding to the compound. Then, an MS image at the m/z value is created and displayed on a screen. On the other hand, in a case in which the target compound is not specified, a user designates an appropriate peak while viewing an acquired mass spectrum. Then, the imaging mass spectrometer creates an MS image corresponding to the m/z value of the designated peak and displays the MS image on the screen. In such a case, as described in Patent Literature 1, an average mass spectrum created by averaging a plurality of mass spectra obtained in all micro regions in a measurement region or a sum mass spectrum obtained by simply summing the plurality of mass spectra is often used as the mass spectrum for the user to select the peak. This is because it is considered that the average mass spectrum or the sum mass spectrum usually contains information about all compounds present in the measurement region. CITATION LIST Patent Literature Patent Literature 1: JP 2011-191222 APatent Literature 2: WO 2015/053039 A SUMMARY OF INVENTION Technical Problem However, the analysis method in the conventional imaging mass spectrometer has the following problems. The above average mass spectrum is obtained by averaging so-called profile spectra each of which is created on the basis of raw data obtained by mass spectrometry on a micro region in the measurement region. The width of a peak observed in a profile spectrum depends on the mass resolution of a mass spectrometer used for measurement. Although a time-of-flight mass spectrometer (TOFMS) widely used in the imaging mass spectrometer generally has high mass accuracy, a typical TOFMS in many cases cannot completely separate peaks derived from different compounds having masses very close to each other by its mass resolution. A Fourier transform mass spectrometer, on the other hand, generally has a very high mass resolution. However, in a case in which a sample contains a large number of compounds having masses very close to each other, it is difficult to sufficiently separate peaks of such compounds. When an average mass spectrum is created from such a plurality of profile spectra having poor separability, peaks having m/z values close to each other often overlap to form substantially one peak. The m/z value obtained from such a peak is often different from any of the m/z values corresponding to the plurality of overlapping compounds. That is, information (masses and signal intensities) of different compounds which have been recognized by different peaks in the profile spectra may be lost by averaging or summing the mass spectra at a portion in the measurement region. Even in a case where the mass resolution is high to some extent, a peak in a profile spectrum may have a large skirt. Therefore, when a difference in m/z value between a peak observed in a profile spectrum A for a certain micro region and a peak observed in a profile spectrum B for another micro region is small and a signal intensity difference between these peaks is large, the pe