Combined DESI and optical imaging analysis of tissues

Patent metadata

Field	Value
Publication number	US-9921233-B2
Application number	US-201514880623-A
Country	US
Kind code	B2
Filing date	Oct 12, 2015
Priority date	May 18, 2011
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

The invention generally relates to mass spectral analysis. In certain embodiments, methods of the invention involve analyzing a lipid containing sample using a mass spectrometry technique, in which the technique utilizes a liquid phase that does not destroy native tissue morphology during analysis.

First claim

What is claimed is:

1. A method for analyzing a tissue sample, the method comprising:
performing a mass spectral analysis of a tissue sample using a desorption electrospray ionization (DESI) technique that comprises directing a liquid phase that does not destroy native tissue morphology from a DESI probe onto the tissue sample to thereby desorb one or more lipids, peptides, or proteins from the sample that are analyzed by a mass spectrometer;
producing a mass spectral image of the tissue sample based on results of the mass spectral analysis;
performing a histochemistry analysis technique on the sample to thereby stain the sample;
producing an optical image of the stained sample;
overlaying the mass spectral image with the optical image of the stained sample to produce an overlaid image; and
determining a distribution of the one or more lipids, peptides, or proteins in the tissue sample based on an analysis of the overlaid image.

2. The method of claim 1 , wherein the liquid phase is a solvent comprising dimethylformamide (DMF), acetonitrile (ACN), or tetrahydrofuran (THF).

3. The method according to claim 2 , wherein the liquid phase comprises at least one other component.

4. The method according to claim 3 , wherein the at least one other component is selected from the group consisting of ethanol (EtOH), water (H 2 O), acetonitrile (ACN), and a combination thereof.

5. The method according to claim 1 , wherein the liquid phase is selected from the group consisting of: acetonitrile (ACN):ethanol (EtOH); methanol (MeOH):chloroform (CHCl 3 ); and acetonitrile (ACN):chloroform (CHCl 3 ).

6. The method according to claim 1 , wherein the histochemistry analysis technique is H&E staining.

7. The method according to claim 1 , wherein the one or more lipids are analyzed by the mass spectrometer.

8. The method according to claim 1 , wherein the ionization probe is a desorption electrospray ionization probe.

9. The method according to claim 1 , further comprising determining whether an abnormality exists in the tissue sample based on the distribution of the one or more lipids, peptides, or proteins in the tissue sample.

10. The method according to claim 9 , wherein the abnormality is a cancer.

11. A method for detecting cancerous tissue within a tissue sample, the method comprising:
performing a mass spectral analysis of a tissue sample using a desorption electrospray ionization (DESI) technique that comprises directing a liquid phase that does not destroy native tissue morphology from lipids, peptides, or proteins a DESI probe onto the tissue sample to thereby desorb one or more lipids, peptides, or proteins from the sample that are analyzed by a mass spectrometer;
producing a mass spectral image of the tissue sample based on results of the mass spectral analysis;
performing a histochemistry analysis technique on the sample to thereby stain the sample;
producing an optical image of the stained sample;
overlaying the mass spectral image with the optical image of the stained sample to produce an overlaid image; and
detecting cancerous tissue within the tissue sample based on an analysis of the overlaid image.

12. The method of claim 11 , wherein the liquid phase is a solvent comprising dimethylformamide (DMF), acetonitrile (ACN), or tetrahydrofuran (THF).

13. The method according to claim 12 , wherein the liquid phase comprises at least one other component.

14. The method according to claim 13 , wherein the at least one other component is selected from the group consisting of ethanol (EtOH), water (H 2 O), acetonitrile (ACN), and a combination thereof.

15. The method according to claim 11 , wherein the liquid phase is selected from the group consisting of: acetonitrile (ACN):ethanol (EtOH); methanol (MeOH):chloroform (CHCl 3 ); and acetonitrile (ACN):chloroform (CHCl 3 ).

16. The method according to claim 11 , wherein the histochemistry analysis technique is H&E staining.

17. The method according to claim 11 , wherein the one or more lipids are analyzed by the mass spectrometer.

18. The method according to claim 11 , wherein the ionization probe is a desorption electrospray ionization probe.

19. The method according to claim 11 , wherein the desorption electrospray ionization probe operates at atmospheric pressure and temperature.

Assignees

• Purdue Research Foundation

Inventors

• Cooks Robert Graham
• Eberlin Livia Schiavinato
• Ferreira Christina Ramires
• Dill Allison Lisa
• Ifa Demian R

Classifications

• H01J49/142

  using a solid target which is not previously vapourised · CPC title

• G01N33/92 Primary

  involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} · CPC title

• H01J49/0036

  Step by step routines describing the handling of the data generated during a measurement · CPC title

• H01J49/0004

  Imaging particle spectrometry · CPC title

• H01J49/165

  Electrospray ionisation · CPC title