Methods and apparatuses for analyzing biological samples by mass spectrometry

• US 8,778,695 B2
• Filed: 06/29/2004
• Issued: 07/15/2014
• Est. Priority Date: 10/15/2001
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Caprioli, Richard
• Primary Examiner(s): Gakh, Yelena G
• Application Number:
  US10/880,750
• Publication Number:
  US 20050029444A1
• Time in Patent Office: 3,668 Days
• Field of Search: None
• US Class Current: 436/173
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6848 Methods of protein analysis involving mass spectrometry
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Methods and apparatuses for analyzing proteins and other biological materials and xenobiotics within a sample. A specimen is generated, which may include an energy absorbent matrix. The specimen is struck with laser beams such that the specimen releases proteins. The atomic mass of the released proteins over a range of atomic masses is measured. An atomic mass window of interest within the range of atomic masses is analyzed to determine the spatial arrangement of specific proteins within the sample, and those specific proteins are identified as a function of the spatial arrangement. By analyzing the proteins, one may monitor and classify disease within a sample.

Claims

1. A method of assessing a state of disease or tissue development in a specimen from a subject, comprising:

(a) generating a solid state first specimen that has not been subjected to homogenization, release of cellular components, centrifugation or cell fractionation;

(b) subjecting a first spot of a first specimen to desorption ionization to release a first plurality of proteins;

(c) obtaining a first set of data comprising positional information on the first spot and a mass spectrum of the first plurality of proteins;

(d) moving the first specimen a predetermined linear distance or generating a second solid state specimen, wherein the second specimen comprises a tissue that is related to the first specimen in time or tissue type;

(e) subjecting a second spot of the first or the second specimen to desorption ionization to release a second plurality of proteins;

(f) obtaining a second set of data comprising positional information on the second spot and a mass spectrum of the second plurality of proteins;

(g) comparing the first data set with the second data set and identifying protein molecular changes and positional changes between the first and second spots; and

(h) assessing a state of a disease or tissue development in the subject based on the identified protein molecular and positional changes.