Spatial Tissue State Differentiation via Mass Spectrometry
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Solution Overview
Problem
Current methods for determining and visualizing tissue states in histologic tissue sections using mass spectrometry are limited by the need for extensive sample preparation, difficulty in obtaining sufficient material, and the inability to analyze complex patterns of peptides and proteins for early disease prediction, particularly in distinguishing between healthy and diseased tissue within a single individual.
Innovation Solution
A method that involves producing histologic tissue sections, preparing them for mass spectrometric analysis, detecting spatially resolved mass spectrometric signals, calculating localized characteristics to distinguish between different tissue states, and graphically representing these characteristics for visual representation, using computational methods developed from cohort data to differentiate healthy and diseased tissue, and applying these characteristics directly to the tissue images.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional mass spectrometry methods are used for tissue analysis, then molecular weight determination and protein identification can be achieved, but extensive sample preparation is required and sufficient material is difficult to obtain
Solution Approach 1:
The patent extracts and analyzes proteins directly from tissue sections without requiring extensive extraction and purification steps. By using mass spectrometry to detect proteins in situ, the method eliminates time-consuming sample preparation while maintaining the ability to identify proteins and determine their spatial distribution in the tissue.
Solution Approach 2:
The patent creates a mass spectrometric map that copies the spatial distribution of proteins from the tissue section. This mass spectral image serves as a representation of the tissue's protein composition, allowing analysis without physically manipulating or extracting the proteins from their native locations.
2Measurement precision
If traditional mass spectrometry methods are used for tissue analysis, then molecular weight determination can be achieved, but the ability to analyze complex patterns of peptides and proteins for early disease prediction is limited
Solution Approach 1:
The patent adds a spatial dimension to mass spectrometry analysis by mapping the locations of different peptides and proteins across the tissue section. This transforms the analysis from one-dimensional (mass spectra only) to two-dimensional (spatial distribution), enabling the detection of localized tissue states and patterns that indicate early disease processes.
Solution Approach 2:
The patent analyzes local variations in peptide and protein composition across different regions of the tissue section. By examining the spatial distribution and relative abundances of specific mass spectral features, the method identifies localized tissue states that differ from normal tissue, providing information about early disease processes without requiring loss of spatial context.
3Loss of information
If laser capture microdissection is used to obtain tissue regions, then spatial information can be preserved, but time-consuming processing is still required and sufficient material is difficult to obtain
Solution Approach 1:
The patent creates a mass spectrometric copy of the tissue section's protein composition and spatial distribution. Instead of physically cutting and isolating tissue regions, the method uses mass spectrometry to generate a spectral map that represents the tissue's molecular content in situ, preserving spatial information without requiring physical manipulation or sufficient material for isolation.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Enables more precise and efficient visualization of tissue states and differentiation between healthy and diseased tissue within a single individual, reducing the need for extensive cohort analysis and improving the detection of subtle differences in tissue characteristics.
Implementation Method 1
Bombarding the sample obtained in this way with sufficiently energetic short pulses of laser light leads to the matrix substance absorbing energy and evaporating explosively as a result. The proteins are entrained into the gaseous cloud inside the mass spectrometer and ionized by protonation.
Implementation Method 2
Mass spectrometry with ionization of the samples by matrix-assisted laser desorption and ionization (MALDI)
Data Source
AI summary
The invention relates to the determination and visualization of the spatial distribution of tissue states in histologic tissue sections on the basis of mass spectrometric signals acquired so as to be spatially resolved. The invention provides a method which determines the tissue state for the tissue spots as a state characteristic, which is calculated as a mathematical or logical expression from at least two mass signals of this tissue spot, and which indicates the tissue state as a gray-level or false-color image in one or two dimensions.