Imaging mass spectrometry system and analytical method using imaging mass spectrometry

Patent metadata

Field	Value
Publication number	US-11469087-B2
Application number	US-202017113544-A
Country	US
Kind code	B2
Filing date	Dec 7, 2020
Priority date	Mar 23, 2020
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

Imaging mass spectrometry section (100) performs a mass spectrometric analysis at each of the micro areas set within a measurement area on a target sample, and acquires a graphical image showing a signal-intensity distribution at a specific mass-to-charge ratio or mass-to-charge-ratio range. Quantitative analysis section (300) determines a quantitative value using an analysis result obtained by performing an analysis on the sample collected from each predetermined site within the measurement area of the target sample, using a predetermined analytical technique exhibiting a higher level of quantitative determination performance than the mass spectrometric analysis. Processing section (400) determines the relationship between signal intensity and quantitative value, based on quantitative values determined for the sample at predetermined sites and signal intensities at positions corresponding to the predetermined sites in the signal-intensity distribution, and estimates the quantitative value at an arbitrary position within the signal-intensity distribution, using the relationship.

First claim

The invention claimed is:

1. An imaging mass spectrometry system, comprising:
an imaging mass spectrometry section configured to collect data by performing a mass spectrometric analysis for each of a plurality of micro areas set within a measurement area on a target sample, and to acquire, based on the data, an image showing a distribution of a signal intensity for a specific mass-to-charge ratio or mass-to-charge-ratio range;
a quantitative analysis sample preparing section configured to prepare a quantitative analysis sample by collecting a sample component from a predetermined site within the measurement area or a virtual measurement area corresponding to the measurement area of the target sample or an analogous sample which is not the target sample and yet is considered as virtually identical to the target sample in terms of a distribution of a substance;
a quantitative analysis section configured to perform a second analysis on the quantitative analysis sample by a predetermined analytical technique which exhibits a higher level of quantitative determination performance than the mass spectrometric analysis by the imaging mass spectrometry section, and to determine a quantitative value using a result of the second analysis; and
a processing section configured
to determine a relationship between the signal intensity acquired by the imaging mass spectrometry section and the quantitative value acquired by the quantitative analysis section, based on the quantitative value determined for the quantitative analysis sample at the predetermined site by the quantitative analysis section and the signal intensity at a position corresponding to the predetermined site within the distribution of the signal intensity acquired by the imaging mass spectrometry section, and
to estimate a quantitative value at an arbitrary position within the distribution of the signal intensity using the determined relationship.

2. The imaging mass spectrometry system according to claim 1 , wherein the predetermined analytical technique is one of following techniques: liquid chromatographic analysis, gas chromatographic analysis, liquid chromatograph mass spectrometry, gas chromatograph mass spectrometry, matrix-assisted laser desorption/ionization mass spectrometry, Raman spectroscopic analysis, infrared spectroscopic analysis, ultraviolet-visible spectroscopic analysis, fluorescent analysis, and staining quantification.

3. The imaging mass spectrometry system according to claim 1 , further comprising a quantification-site determination section configured to determine the predetermined site from which a sample to be analyzed by the quantitative analysis section is to be collected, using a mass spectrometric imaging graphic showing a distribution of the signal intensity at one or more specific mass-to-charge ratios acquired by the imaging mass spectrometry section.

4. The imaging mass spectrometry system according to claim 3 , wherein: the target sample is a sample section in a form of a slice cut from a lump of sample; the sample to be analyzed by the quantitative analysis section is the analogous sample; and the analogous sample is another sample section located next to or close to the target sample.

5. The imaging mass spectrometry system according to claim 4 , further comprising an image transformation section configured to perform image transformation by image registration on a mass spectrometric imaging graphic or observation image obtained for the target sample as well as an observation image before sample collection in the analogous sample, wherein the quantification-site determination section is configured to use the graphic and the image after the transformation when determining the predetermined site from which a sample to be quantitatively analyzed is to be collected.

6. The imaging mass spectrometry system according to claim 5 , wherein: the image transformation section is configured to transform the mass spectrometric imaging graphic obtained for the target sample so that the graphic fits to the observation image before sample collection in the analogous sample; and the quantification-site determination section is configured to determine the predetermined site from which a sample to be quantitatively analyzed is to be collected, by relating an area set on the transformed mass spectrometric imaging graphic to an area on the observation image before sample collection in the analogous sample.

7. The imaging mass spectrometry system according to claim 5 , wherein the area set on the mass spectrometric imaging graphic after the transformation by the image transformation section is set as a region of interest when the data collected by the imaging mass spectrometry section is analyzed.

8. An analytical method using imaging mass spectrometry, comprising:
a first analysis execution step configured to perform an imaging mass spectrometric analysis for a measurement area on a target sample, and to acquire an image showing a distribution of a signal intensity for a specific mass-to-charge ratio or mass-to-charge-ratio range;
a quantitative analysis sample preparing step configured to prepare a quantitative analysis sample by collecting a sample component from a predetermined site within the measurement area or a virtual measurement area corresponding to the measurement area of the target sample or an analogous sample which is not the target sample and yet is considered as virtually identical to the target sample in terms of a distribution of a substance;
a second analysis execution step configured to perform a second analysis on the quantitative analysis sample by a predetermined analytical technique which exhibits a higher level of quantitative determination performance than the analysis by the first analysis execution step, and to determine a quantitative value using a result of the second analysis; and
a processing step configured to determine a relationship between the signal intensity acquired by the imaging mass spectrometric analysis and the quantitative value acquired by the second analysis using the predetermined analytical technique, based on the quantitative value determined for the quantitative analysis sample at the predetermined site in the second analysis execution step and the signal intensity at a position corresponding to the predetermined site within the distribution of the signal intensity acquired in the first analysis execution step, and to estimate a quantitative value at an arbitrary position within the distribution of the signal intensity using the determined relationship.

9. The analytical method using imaging mass spectrometry according to claim 8 , wherein the predetermined analytical technique is one of following techniques: liquid chromatographic analysis, gas chromatographic analysis, liquid chromatograph mass spectrometry, gas chromatograph mass spectrometry, matrix-assisted laser desorption/ionization mass spectrometry, Raman spectroscopic analysis, infrared spectroscopic analysis, ultraviolet-visible spectroscopic analysis, fluorescent analysis, and staining quantification.

10. The analytical method using imaging mass spectrometry according to claim 8 , further comprising a quantification-site determination step configured to determine the predetermined site from which a sample to be quantitatively analyzed in the second analysis execution step is to be collected, using a mass spectrometric imaging graphic showing a distribution of the signal intensity at one or more specific mass-to-charge ratios acquired in the first analysis execution step.

11. The analytical method using imaging mass spectrometry according to claim 10 , wherein: the target sample is a sample section in a form of a slice cut from a

Assignees

• Shimadzu Corp

Inventors

• Yamaguchi Shinichi
• Yamamoto Takushi

Classifications

• G01N21/6486

  Measuring fluorescence of biological material, e.g. DNA, RNA, cells (G01N21/6428 takes precedence) · CPC title

• G01N21/33

  using ultraviolet light (G01N21/39 takes precedence) · CPC title

• G01N21/3577

  for analysing liquids, e.g. polluted water · CPC title

• G01N21/314

  with comparison of measurements at specific and non-specific wavelengths (dual wavelength spectrometry G01J3/427) · CPC title

• G01N1/2813

  Producing thin layers of samples on a substrate, e.g. smearing, spinning-on (G01N1/30 takes precedence) · CPC title