Information acquisition method, information acquisition apparatus and disease diagnosis method

• US 20060183235A1
• Filed: 12/28/2005
• Published: 08/17/2006
• Est. Priority Date: 07/02/2003
• Status: Active Grant

• Current Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Original Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Inventors: Ban, Kazuhiro, Kuge, Katsuaki, Hashimoto, Hiroyuki, Okamoto, Tadashi, Komatsu, Manabu, Imamura, Takeshi, Kobayashi, Shin, Nakamura, Kumi
• Granted Patent: US 7,701,138 B2
• Time in Patent Office: Days
• US Class Current: 436/86
• CPC Class Codes: G01N 33/4833 of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry

Abstract

An information acquisition method for acquiring information on a target object, that includes a step of promoting ionization of the target object using a substance for promoting ionization of the target object to cause the target object to emit, and a step of acquiring information on the mass of the flew target object using time-of-flight secondary ion mass spectrometry.

Claims

1. An information acquisition method for acquiring information on a target object, characterized in that it comprises the steps of:

promoting ionization of the target object using a substance for promoting ionization of the target object to cause the target object to emit; and

acquiring information on the mass of the flew target object using a time-of-flight secondary ion mass spectrometry.

2. The information acquisition method according to claim 1, wherein the target object is a protein.

3. The information acquisition method according to claim 1, wherein the flew target object is any of:

(1) an ion corresponding to a parent molecule of the target object;

(2) an ion corresponding to a mass obtained by addition to a parent molecule of the target object of an atom or a cluster of a specific metal element;

(3) an ion corresponding to a mass obtained by addition to a parent molecule of the target object of an atom or a cluster of a specific metal element and further addition thereto of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen;

(4) an ion corresponding to a mass obtained by addition to a parent molecule of the target object of an atom or a cluster of a specific metal element, and further addition thereto of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen, and elimination therefrom of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen;

(5) an ion corresponding to a mass obtained by addition to a partial structure of the target object of an atom or a cluster of a specific metal element;

(6) an ion corresponding to a mass obtained by addition to a partial structure of the target object of an atom or a cluster of a specific metal element, and further addition thereto of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen; and

(7) an ion corresponding to a mass obtained by addition to a partial structure of the target object of an atom or an cluster of a specific metal element, and further addition thereto of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen, and elimination therefrom of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen.

4. The information acquisition method according to claim 1, wherein information on a state of two-dimensional distribution of the target object obtained by scanning of a primary ion is acquired based on a result of detection of the flew target object.

5. The information acquisition method according to claim 1, wherein the step of promoting ionization of the target object is comprised of the steps of:

contacting the target object and the substance for promoting ionization, and then irradiating a primary ion on the contacted part.

6. The information acquisition method according to claim 5, wherein the contacting step is performed utilizing a silver mirror reaction.

31. The information acquisition method according to claim 1, wherein the target object is a content of cell.

32. The information acquisition method according to claim 31, the content of cell is a metabolite.

33. The information acquisition method according to claim 32, the metabolite is a drug metabolite.

34. The information acquisition method according to claim 31, wherein a mass of the content of cell falls within the range of 50 to 2000.

7. An information acquisition apparatus for acquiring information on a target object using time-of-flight secondary ion mass spectrometry, characterized in that the apparatus comprises a means for contacting the target object with a substance for promoting ionization of the target object and a means for irradiating with an ion beam an area of contact between the target object and the substance for promoting ionization of the target object, wherein information on the mass of the target object at least one part of which object was ionized is acquired by the irradiation from the irradiating means.

8. An information acquisition method for acquiring information on the mass of a target object using a time-of-flight mass spectrometer, characterized in that it comprises the steps of:

applying a substance for promoting ionization of the target object;

ionizing the target object using a focused, pulsed and scannable primary beam to cause the target object to emit; and

acquiring information on the mass of the flew target object using a time-of-flight mass spectrometer.

9. The information acquisition method according to claim 8, wherein the primary beam is an ion beam.

10. The information acquisition method according to claim 8, wherein the step of applying a substance for promoting ionization of the target object is a step using an aqueous solution comprising an ionization-promoting substance, and is conducted in a one-step process.

11. The information acquisition method according to claim 10, wherein the substance for promoting ionization of the target object is a water-soluble substance.

12. The information acquisition method according to claim 10, wherein the substance for promoting ionization of the target object is comprised of an atom of at least one selected from the group consisting of noble metals and alkali metals.

13. The information acquisition method according to claim 12, wherein the substance for promoting ionization of the target object is comprised of an atom of either Ag or Na.

14. The information acquisition method according to claim 8, wherein the information on the mass of a target object is information on a mass of any of:

(1) an ion corresponding to a mass obtained by addition to the mass of a parent molecule of the target object of the mass of an atom of at least one selected from the group consisting of noble metals and alkali metals;

(2) an ion corresponding to a mass obtained by addition to the mass of a parent molecule of the target object of the mass of an atom of at least one selected from the group consisting of noble metals and alkali metals and further addition thereto of the mass of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen;

(3) an ion corresponding to a mass obtained by addition to the mass of a parent molecule of the target object of the mass of an atom of at least one selected from the group consisting of noble metals and alkali metals and further addition thereto of the mass of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen, and elimination therefrom of the mass of any number of from 1 to 10 atoms of at least one selected from the group consisting of hydrogen, carbon, nitrogen and oxygen.

15. The information acquisition method according to claim 8, wherein at least one step of a step of preparing the target object and the step of applying a substance for promoting ionization of the target object is conducted by applying droplets.

16. The information acquisition method according to claim 15, wherein the droplet is comprised of water and a surfactant.

17. An information acquisition method for acquiring information on the mass of a constituent of a target object using a time-of-flight mass spectrometer to obtain information on a distribution of the constituent based on the acquired information, characterized in that the method comprises the steps of:

preparing a sample comprising a constituent of tissue from a living organism as the target object;

conducting a treatment for promoting ionization of an ionic species deriving from the constituent;

irradiating the target object with a focused ion beam to cause the ionic species deriving from the constituent to emit; and

measuring an intensity of the flew ionic species using a time-of-flight mass spectrometer to obtain information on a distribution of the constituent based on the measured value.

18. The information acquisition method according to claim 17, wherein the treatment for promoting ionization is the application of a substance for promoting ionization of the ionic species deriving from the constituents to the constituent.

19. The information acquisition method according to claim 17, wherein the treatment for promoting ionization is the decomposition of the constituent by a digestive enzyme.

20. The information acquisition method according to claim 17, wherein the treatment for promoting ionization consists of both the decomposition of the constituent by a digestive enzyme and the application of a substance for promoting ionization of the ionic species deriving from the constituents to the constituent.

21. The information acquisition method according to claim 20, wherein both the decomposition and the application are carried out by an ink-jet method.

22. A disease diagnosis method, characterized in that diagnosis of a disease is conducted by utilizing the information acquisition method according to claim 17.

23. The disease diagnosis method according to claim 22, wherein a protein is comprised in the constituent of tissue from a living organism, and the diagnosis is conducted by utilizing a state of distribution of a flew ionic species that derive from a peptide of a mass in a range of 500 to 5000 comprised in the protein.

36. A method for detecting whether a substance particular to a disease exists in a specimen or not which utilizes the information acquisition method according to claim 17.

24. An information acquisition method for acquiring information on the mass of a constituent of a target object using a time-of-flight mass spectrometer to obtain information on a distribution of the constituent based on the acquired mass information, characterized in that the method comprises the steps of:

preparing a sample comprising a constituent of tissue from a living organism;

contacting the sample with the surface of a substrate to transfer at least one part of the constituent to the substrate;

irradiating a focused ion beam onto the substrate to which at least one part of the constituent was transferred as the target object to cause an ionic species deriving from the constituent to emit; and

measuring an intensity of the flew ionic species using a time-of-flight mass spectrometer to obtain information on a distribution of the constituent based on the measured value.

25. The information acquisition method according to claim 24, wherein the surface of the substrate with which the sample is contacted comprises a substance for promoting ionization of the ionic species deriving from the constituents.

26. The information acquisition method according to claim 24, wherein the surface of the substrate with which the sample is contacted has chemically treated for promoting transfer of the constituent to the substrate.

27. The information acquisition method according to claim 26, wherein the chemical treatment is the introducing of a maleimide group onto the substrate surface.

28. A disease diagnosis method, characterized in that diagnosis of a disease is conducted by utilizing the information acquisition method according to claim 24.

29. The disease diagnosis method according to claim 28, wherein a protein is comprised in the constituent of tissue from a living organism, and the diagnosis is conducted by utilizing a state of distribution of a flew ionic species that derive from a peptide of a mass in a range of 500 to 5000 comprised in the protein.

35. The information acquisition method according to claim 24, wherein the constituent of tissue from a living organism is a cell.

37. A method for detecting whether a substance particular to a disease exists in a specimen or not which utilizes the information acquisition method according to claim 24.

30. An information acquisition apparatus that acquires information on the mass of a constituent comprised of a target object using a time-of-flight mass spectrometer to obtain information on a distribution of the constituents based on the acquired mass information, characterized in that it comprises:

a means for contacting the constituents with a substrate surface to transfer at least one part of the constituents to the substrate side;

a time-of-flight mass spectrometer that employs the substrate to which at least one part of the constituent was transferred as the target object, and irradiates the target object with a focused ion beam to cause ionic species deriving from the constituents to emit to measure intensities of the flew ionic species; and

a means for analyzing a measurement result for obtaining information on a distribution state of the constituents based on the measured value.