Methods for determining a tumor margin in a tissue using a desorption electrospray ionization (desi) technique

Patent metadata

Field	Value
Publication number	US-11397189-B2
Application number	US-201715407876-A
Country	US
Kind code	B2
Filing date	Jan 17, 2017
Priority date	May 18, 2011
Publication date	Jul 26, 2022
Grant date	Jul 26, 2022

Abstract

The invention generally relates to methods for analyzing a metabolite level in a sample. In certain embodiments, methods of the invention may involve obtaining a sample, analyzing the sample using a mass spectrometry technique to determine a level of at least one metabolite in the sample, and correlating the metabolite level with an originating source of the sample, thereby analyzing the sample.

First claim

What is claimed is:

1. A method for determining a tumor margin, the method comprising:
depositing a tissue sample onto a substrate, wherein the tissue sample comprises at least one metabolite indicative of a cancer at one or more locations of the tissue sample;
conducting a desorption electrospray ionization (DESI) technique on the one or more locations of the tissue sample using a solvent selected from the group consisting of: acetonitrile (ACN):ethanol (EtOH) and acetonitrile (ACN):chloroform (CHCl 3 ) that does not destroy native tissue morphology of the tissue sample in order to desorb the at least one metabolite from the one or more locations of the tissue sample and direct the at least one metabolite into a mass spectrometer to thereby generate at least one mass spectral signal of the at least one metabolite from the one or more locations;
performing a histochemistry analysis technique on the tissue sample to stain the tissue sample and produce an optical image of the stained tissue sample;
overlaying spatial molecular information derived from the at least one mass spectral signal onto the optical image of the stained tissue sample to produce an overlaid image; and
defining one or more tumor margins between cancerous and non-cancerous tissue based on the overlaid image.

2. The method according to claim 1 , wherein the DESI technique is performed without prior sample preparation.

3. The method according to claim 1 , wherein the tissue sample is from a frozen tissue sample.

4. The method according to claim 1 , wherein the tissue sample is a human tissue sample.

5. The method according to claim 4 , wherein the human tissue sample is a distribution of cells and extracellular matrix that is spread on the substrate.

6. The method according to claim 1 , wherein the histochemistry analysis technique is Haemotoxylin and Eosin (H&E) staining.

7. The method according to claim 1 , wherein the DESI technique is performed in a negative ion mode.

Assignees

• Purdue Research Foundation

Inventors

• Cooks Robert Graham
• Kerian Kevin Scott
• Jarmusch Alan Keith
• Hamid Ahmed Mohamed
• Eberlin Livia Schiavinato

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

• H01J49/0004

  Imaging particle spectrometry · CPC title

• G01N2560/00

  Chemical aspects of mass spectrometric analysis of biological material · CPC title

• G01N33/50 Primary

  Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) · CPC title