IP Library Granted Patent US 11,860,172
Granted Patent B2
US 11,860,172 · App. 17/331,264 · Granted Jan 2, 2024

Mass spectral tissue analysis

Inventors: Robert Graham Cooks (West Lafayette, IN); Livia Schiavinato Eberlin (Lafayette, IN); Christina Ramires Ferreira (West Lafayette, IN); Allison Lisa Dill (Indianapolis, IN); Demian R. Ifa (West Lafayette, IN)
Assignee: Purdue Research Foundation
G01N33/92H01J49/0036H01J49/165H01J49/0004H01J49/142
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Quick Facts
Patent No.
US 11,860,172
App. No.
17/331,264
Granted
Jan 2, 2024
Kind
B2
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. Due to the use of a liquid phase that does not destroy native tissue morphology during analysis, a subsequent staining technique can be performed on the tissue sample and an overlaid image can be produced of a mass spectral image and a staining image.

Claims (33)

1. A method for assessing a tissue sample for presence of cancerous cells, the method comprising:

receiving mass spectral data of a tissue sample produced in part via use of a solvent that when in contact with the tissue sample does not destroy native morphology of the tissue sample;

producing a mass spectral image of the tissue sample based on the mass spectral data;

receiving histochemical data of the tissue sample;

producing an optical image of the tissue sample from the histochemical data;

overlaying the mass spectral image of the tissue sample with the optical image of the tissue sample to produce an overlaid image; and

assessing the overlaid image for presence of cancerous cells.

2. The method according to claim 1 , wherein assessing comprises determining a distribution of one or more compounds in the tissue sample based on an analysis of the overlaid image.

3. The method according to claim 1 , wherein the mass spectral data is produced 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 compounds from the tissue sample that are analyzed by a mass spectrometer.

4. The method of claim 3 , wherein the liquid phase is the solvent and the solvent comprises dimethylformamide (DMF), acetonitrile (ACN), or tetrahydrofuran (THF).

5. The method according to claim 4 , wherein the liquid phase comprises at least one other component.

6. The method according to claim 5 , 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.

7. The method according to claim 3 , 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 ).

8. The method according to claim 1 , wherein the histochemical data is produced by H&E staining.

9. The method according to claim 3 , wherein the one or more compounds comprises one or more lipids.

10. The method according to claim 2 , further comprising grading the cancerous cells based on the distribution of the one or more compounds in the tissue sample.

11. The method according to claim 10 , wherein the cancerous cells are indicative of brain or bladder cancer.

12. A method for assessing a tissue sample for presence of cancerous cells, the method comprising:

receiving mass spectral data of a tissue sample comprising a cancerous section produced in part via use of a solvent that when in contact with the tissue sample does not destroy native morphology of the tissue sample;

producing a mass spectral image of the tissue sample comprising the cancerous section based on the mass spectral data;

receiving histochemical data of the tissue sample comprising the cancerous section;

producing an optical image of the tissue sample comprising the cancerous section from the histochemical data;

overlaying the mass spectral image of the tissue sample comprising the cancerous section with the optical image of the tissue sample comprising the cancerous section to produce an overlaid image;

identifying the cancerous section within the overlaid image; and

assessing the overlaid image to determine a grade of the cancerous section.

13. The method according to claim 12 , wherein the mass spectral data is produced using a desorption electrospray ionization (DESI) technique operated in imaging mode.

14. The method according to claim 13 , wherein the mass spectral data is produced using a 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 compounds from the tissue sample that are analyzed by a mass spectrometer.

15. The method of claim 14 , wherein the liquid phase is the solvent and the solvent comprises dimethylformamide (DMF), acetonitrile (ACN), or tetrahydrofuran (THF).

16. The method according to claim 15 , wherein the liquid phase comprises at least one other component.

17. The method according to claim 16 , 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.

18. The method according to claim 14 , 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 ).

19. The method according to claim 12 , wherein the histochemical data is produced by H&E staining.

20. The method according to claim 14 , wherein the one or more compounds comprises one or more lipids.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 5, 2023
From: PURDUE UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065775/0470 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 26, 2021
From: COOKS, ROBERT GRAHAM; EBERLIN, LIVIA SCHIAVINATO; FERREIRA, CHRISTINA RAMIRES; DILL, ALLISON LISA; IFA, DEMIAN R.
To: PURDUE RESEARCH FOUNDATION
Reel/Frame 057295/0765 →
Continuity (5)
Continuation 15891793 · Feb 8, 2018
Continuation 14880623 · Oct 12, 2015
Continuation 13475305 · May 18, 2012
Provisional Application 61487363 · May 18, 2011
Related Publication 20210356480A1 · Nov 18, 2021