# US 8,569,690 B2 · Method of forming mass image

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- Number: US 8,569,690 B2
- Document ID: US8569690B2
- Status: Granted
- Kind: B2
- Application number: 13/772,123
- Filed: 2013-02-20
- Published: 2013-06-20
- Granted: 2013-10-29
- Earliest claimed: 2009-04-10
- Assignees: Canon Kabushiki Kaisha
- Applicants: Canon Kabushiki Kaisha
- Inventors: Manabu Komatsu; Hiroyuki Hashimoto
- Web page: https://patentgrep.com/patent/US8569690B2

## CPC

- G16B 45/00: ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
- G01N 33/6848: {Methods of protein analysis involving mass spectrometry}
- H01J 49/0004: {Imaging particle spectrometry}
- Y10T 436/24: Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

An object of the present invention is to provide a method of comprehensively visualizing a constituent in tumor tissue or the like at a cellular level. The present invention provides a method of forming a two-dimensional distribution image of a target constituent based on information on the mass of constituents of the tissue section wherein, as the internal standard material, any one of actin, tubulin and GAPDH is used in the intracellular region, one of histone and nucleic acid is used in the nuclear region, and one of albumin and cytokine is used in the extracellular region.

## Claims

### Claim 1

A method of forming a two-dimensional distribution image of a target constituent in constituents of a biological sample based on mass spectra of the biological sample, comprising:
determining a region to which the mass spectra belong, wherein the region is selected from the group consisting of an intracellular region, a nuclear region, and an extracellular region;
calculating, for each region determined in the previous region determination, a normalized intensity of the mass derived from the target constituent from a mass signal intensity derived from the target constituent in a mass spectrum of the constituents and a mass signal intensity derived from an internal standard material in the constituents; and
forming the two-dimensional distribution image of the target constituent based on the normalized intensity of the mass derived from the target constituent,
wherein the internal standard material is selected for each of the regions.

### Claim 2 (depends on 1)

The method according to claim 1, wherein a material stably present in each of the regions is selected as the internal standard material for the region.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the mass spectrum of the constituents is measured by the TOF-SIMS method.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the information on the mass of the constituents is based on the information for each pixel having a length of one side of 5 μm or less.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the region is selected from the group consisting of an intracellular region and an extracellular region.