IP Library Granted Patent US 8,362,415
Granted Patent B2
US 8,362,415 · App. 12/788,146 · Granted Jan 29, 2013

Imaging mass spectrometer with mass tags

Inventors: James S. Felton (Danville, CA); Kuang Jen J. Wu (Cupertino, CA); Mark G. Knize (Tracy, CA); Kristen S. Kulp (Livermore, CA); Joe W. Gray (San Francisco, CA)
Assignees: Lawrence Livermore National Security, LLC; Lawrence Berkeley National Laboratory
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Quick Facts
Patent No.
US 8,362,415
App. No.
12/788,146
Granted
Jan 29, 2013
Kind
B2
Abstract

A method of analyzing biological material by exposing the biological material to a recognition element, that is coupled to a mass tag element, directing an ion beam of a mass spectrometer to the biological material, interrogating at least one region of interest area from the biological material and producing data, and distributing the data in plots.

Claims (42)

1. A method of analyzing biological material wherein said biological material has a region of interest, comprising the steps of:

exposing the biological material to a recognition element,

exposing the biological material to a mass tag element,

exposing said recognition element, said mass tag element, and the biological material to a cleavable linker resulting in said recognition element and said mass tag element, being connected by said cleavable linker,

cleaving said cleavable linker,

using a time-of-flight secondary ion mass spectrometer for directing an ion beam of said time-of-flight secondary ion mass spectrometer to the biological material producing secondary ions, wherein said step of directing an ion beam to the biological material comprises directing an ion beam of a finely focused energetic primary-ion beam of a time-of-flight secondary ion mass spectrometer to the biological material,

interrogating the at least one region of interest area of the biological material by accelerating said secondary ions into said time-of-flight mass spectrometer where they are analyzed for mass by measuring the time-of-flight of said secondary ions from the biological material to the detector,

producing data and

distributing said data in plots including measures of similarity.

2. A method of analyzing biological material wherein said biological material has a region of interest, comprising the steps of:

exposing the biological material to a recognition element,

exposing the biological material to a mass tag element,

exposing said recognition element, said mass tag element, and the biological material to a cleavable linker resulting in said recognition element and said mass tag element, being connected by said cleavable linker,

cleaving said cleavable linker,

using a time-of-flight secondary ion mass spectrometer for directing an ion beam of said time-of-flight secondary ion mass spectrometer to the biological material producing secondary ions, wherein said step of directing an ion beam of said time-of-flight secondary ion mass spectrometer to the biological material comprises directing an ion beam of a matrix-assisted laser desorption/ionization mass spectrometer to the biological material producing secondary ions,

interrogating the at least one region of interest area of the biological material by accelerating said secondary ions into said time-of-flight mass spectrometer where they are analyzed for mass by measuring the time-of-flight of said secondary ions from the biological material to the detector, and

producing data.

3. The method of analyzing biological material of claim 2 further comprising the step of analyzing said data to provide information about the biological material.

4. The method of analyzing biological material of claim 2 further comprising the step of producing a chemical map of the biological material.

5. The method of analyzing biological material of claim 2 further comprising the step of obtaining known data and comparing said data with said known data.

6. The method of analyzing biological material of claim 2 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to a chemical recognition element.

7. The method of analyzing biological material of claim 2 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to a protein recognition element.

8. The method of analyzing biological material of claim 2 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to an antibody recognition element.

9. The method of analyzing biological material of claim 2 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to an oligo recognition element.

10. The method of analyzing biological material of claim 2 wherein said step of exposing the biological material to a mass tag element comprises exposing the biological material to a multiplexed mass tag element.

11. The method of analyzing biological material of claim 2 wherein said steps of exposing the biological material to a recognition element and exposing the biological material to a mass tag element comprises exposing the biological material to a recognition element and a mass tag element that are connected by an ultraviolet light cleavable linker.

12. The method of analyzing biological material of claim 2 wherein said steps of exposing the biological material to a recognition element and exposing the biological material to a mass tag element comprises exposing the biological material to a recognition element and a mass tag element that are connected by an ultraviolet light cleavable linker and including the step of cleaving said cleavable linker by exposing said ultraviolet light cleavable linker to ultraviolet light.

13. A method of analyzing biological material wherein said biological material has a region of interest, comprising the steps of:

exposing the biological material to a recognition element,

exposing the biological material to a mass tag element,

connecting said recognition element and said mass tag element with a cleavable linker,

using a time-of-flight secondary ion mass spectrometer and directing an ion beam of said time-of-flight secondary ion mass spectrometer to the biological material producing secondary ions, wherein said step of directing an ion beam to the biological material comprises directing an ion beam of a finely focused energetic primary-ion beam of a time-of-flight secondary ion mass spectrometer to the biological material,

cleaving said cleavable linker,

interrogating at least one region of interest area from the biological material by accelerating said secondary ions into said time-of-flight mass spectrometer where they are analyzed for mass by measuring the time-of-flight of said secondary ions from the biological material to the detector

producing data, and

analyzing said data to provide information about the biological material, wherein said step of analyzing said data to provide information about the biological material includes distributing said data in plots indicating measures of similarity.

14. The method of analyzing biological material of claim 13 further comprising the steps of obtaining known data and comparing said data with said known data.

15. The method of analyzing biological material of claim 13 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to a chemical recognition element.

16. The method of analyzing biological material of claim 13 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to a protein recognition element.

17. The method of analyzing biological material of claim 13 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to an antibody recognition element.

18. The method of analyzing biological material of claim 13 wherein said step of exposing the biological material to a recognition element comprises exposing the biological material to an oligo recognition element.

19. The method of analyzing biological material of claim 13 wherein said step of exposing the biological material to a mass tag element comprises exposing the biological material to a multiplexed mass tag element.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 26, 2016
From: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 040143/0583 →
CONFIRMATORY LICENSE Recorded Jul 7, 2010
From: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
To: U.S. DEPARTMENT OF ENERGY
Reel/Frame 024642/0680 →
Continuity (2)
Continuation 11713519 · Mar 1, 2007
Related Publication 20100255602A1 · Oct 7, 2010