Inorganic nanoparticle matrices for sample analysis

• US 10,191,028 B1
• Filed: 06/04/2004
• Issued: 01/29/2019
• Est. Priority Date: 06/06/2003
• Status: Active Grant

• Current Assignee: Ionwerks, Inc.
• Original Assignee: Ionwerks, Inc.
• Inventors: Schultz, John Albert, Ugarov, Michael V.
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): Hollinden, Gary E
• Application Number:
  US10/861,970
• Time in Patent Office: 5,352 Days
• Field of Search: 435174, 435176, 435177, 435180-182, 4352877, 4352879, 435DIG 9, 435DIG 11, 435DIG 12, 435DIG 14, 435DIG 15, 435DIG 17, 435DIG 19, 436518, 436524, 436525, 436528, 436531, 436532, 436535, 436173, 436174, 20415761, 20415765, 20415814, 250288, 264 46, 516901, 423445 B, 4222451, 257 53, 257 55, 257E51045, 2525011, 252502, 252503, 252506-509, 252510, 2524081, 252600, 210702, 210710, 118 58, 438510, 438535, 438900, 438914, 438962, 438971, 438974, 585812, 585817, 159DIG 11, 427541, 427903, 376183, 977736, 977738, 977739
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• 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 33/6842 Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• CPC Class Codes: G01N 33/6851 Methods of protein analysis involving laser desorption ionisation mass spectrometry
• CPC Class Codes: H01J 49/0418 for laser desorption, e.g. matrix-assisted laser desorption/ionisation [MALDI] plates or surface enhanced laser desorption/ionisation [SELDI] plates
• CPC Class Codes: H01J 49/164 Laser desorption/ionisation, e.g. matrix-assisted laser desorption/ionisation [MALDI] sample holders H01J49/0418

Abstract

A new type of matrices for Matrix Assisted Laser Desorption and Ionization technique based on derivatized carbon clusters, which will be suitable for the analysis of peptides, proteins and other biomolecules by mass spectrometry which has several advantages over conventional matrices, such as optical sensitivity in a broad spectrum, low interference in the wide mass range and high analyte ionization efficiency.

Claims

1. A method of preparing and analyzing a tissue sample comprising the steps of:

combining the tissue sample with a matrix, said matrix comprising ionized inorganic nanoparticles wherein the combining step further comprises the step of injecting the matrix within a near surface layer of a slice of the tissue sample, wherein the near surface layer comprises a first few nanometers of the slice of the tissue sample, and,

analyzing said combined tissue sample and matrix by laser desorption mass spectrometry.

2. The method of claim 1, wherein the inorganic nanoparticles are selected from the group consisting of nanoparticles of titanium nitride, aluminum nitride, boron nitride, carbonitride, carbon boron nitride, and any combination thereof.

3. The method of claim 1, wherein the inorganic nanoparticles comprise metal.

4. The method of claim 3, wherein said metal is selected from the group consisting of gold, molybdenum, copper, copper lithium alloy, platinum, and any combination thereof.

5. The method of claim 1, wherein the nanoparticles comprise silver clusters.

6. The method of claim 1, wherein the nanoparticles comprise at least one of gold clusters, wide-bandgap nitrides, and transition metal clusters.

7. The method of claim 1, wherein the injecting step comprises manipulating an energy of the ionized inorganic nanoparticles by at least one of adjusting gas pressures and voltages to inject the ionized inorganic nanoparticles into at least a near surface layer of the slice of the tissue sample.

8. The method of claim 1, wherein the tissue sample comprises an analyte.

9. The method of claim 8, wherein the matrix and analyte are combined in a ratio of matrix:

analyte of from 10;

1 to 1;

10000.

10. The method of claim 8, wherein the matrix and analyte are combined in a ratio of matrix:

analyte of from 1;

1 to 1;

1000.

11. The method of claim 8, wherein the analyte comprises protein.

12. The method of claim 11, wherein said protein comprises antibodies or enzymes.

13. The method of claim 8, wherein the analyte comprises a component selected from the group consisting of nucleic acids, oligonucleotides, any constituent components thereof, and any combination of the foregoing.

14. The method of claim 8, wherein the analyte comprises lipoproteins.

15. The method of claim 8, wherein the analyte is a lipid selected from group consisting of phospholipids, ceramides, derivatives thereof, and any combination of the foregoing.

16. The method of claim 8, wherein the analyte comprises a component selected from the group consisting of glycosylated proteins, glycosylated lipids, lipopolysaccharides, glycans, and any combination of the foregoing.

17. The method of claim 8, wherein the analyte comprises synthetic organic polymers, synthetic inorganic polymers, or both.

18. The method of claim 8, wherein the analyte comprises small organic molecules, organometallic molecules, or both.

19. The method of claim 18, wherein said analyte comprises a component selected from the group consisting of herbicides, pesticides, explosives, pharmaceutical drugs, and any combination thereof.

20. The method of claim 8, wherein the analyte is a drug of addiction.

21. The method of claim 20, wherein said drug of addition is selected from the group consisting of cocaine, morphine, heroin, amphetamine and derivatives thereof.