Mass Spectrometry Imaging Quantification via Extinction Coefficient Normalization

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Solution Overview

Problem

Current mass spectrometry techniques require a separate quantification step after molecular imaging, leading to handling and interpretation errors, and fail to provide direct correlation between molecule presence and distribution in samples.

Innovation Solution

The method integrates an extinction coefficient (TEC) into mass spectrometry imaging to normalize signal intensity, allowing direct quantification of target molecules by accounting for variations in sample type and location, using a standard molecule or reference medium to calculate and apply the TEC for accurate concentration measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Difficulty of detecting and measuring

If mass spectrometry imaging is used to detect molecule distribution, then spatial visualization capability is improved, but quantification accuracy deteriorates due to signal intensity variations

Engineering Contradiction:
Improvespatial visualization capabilityVSAvoidquantification accuracy
Core Design Contradiction:
Difficulty of detecting and measuringVSMeasurement precision

Solution Approach 1:

The patent introduces the extinction coefficient (TEC) as a correction parameter that accounts for signal intensity variations caused by different sample matrices and locations. By calculating TEC values for each region and applying them to normalize signal intensities, the method transforms the raw mass spectrometry data into quantitatively accurate concentration measurements while preserving spatial distribution information

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The extinction coefficient acts as an intermediary factor that mediates between the raw signal intensity and the actual molecule concentration. By introducing this intermediate correction factor, the patent bridges the gap between qualitative imaging data and quantitative chemical analysis, enabling accurate concentration determination directly from imaging data

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If separate quantification step is performed after imaging, then quantification capability is improved, but handling and interpretation errors increase

Engineering Contradiction:
Improvequantification capabilityVSAvoidhandling and interpretation errors
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent merges the imaging and quantification functions into a single integrated process. By incorporating TEC-based normalization directly into the mass spectrometry imaging workflow, the method eliminates the need for separate quantification steps, thereby reducing handling and interpretation errors while maintaining both spatial visualization and quantitative capabilities

Inventive Principle:
Principle #5Merging (Combining)

3Loss of information

If direct quantification from imaging data is attempted, then correlation between presence and distribution is improved, but accuracy deteriorates due to signal intensity variations

Engineering Contradiction:
Improvecorrelation between presence and distributionVSAvoidquantification accuracy
Core Design Contradiction:
Loss of informationVSMeasurement precision

Solution Approach 1:

The patent applies parameter transformation by introducing the extinction coefficient to convert raw signal intensity data into accurate concentration information. This parameter change compensates for matrix effects and location-dependent variations, enabling direct quantification from imaging data with both high correlation and high accuracy

Inventive Principle:
Principle #35Parameter changes

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 precise and accurate direct quantification of target molecules on biological tissues, reducing errors and providing a reliable correlation between signal intensity and concentration, independent of sample nature and location.

Implementation Method 1

mass spectrometry imaging, in particular matrix-assisted laser desorption/ionization (MALDI) imaging

Methodology Applied
Scientific EffectLaser desorption/ionization: Laser Ablation

Data Source

PatentEP2689251B1Method for detecting and quantifying a target molecule in a sample
Publication Date: 2019.06.19 IMABIOTECH
  • EP2689251B1 patent drawingFigure 1a~1c
  • EP2689251B1 patent drawingFigure 2a~2b
  • EP2689251B1 patent drawingFigure 3~4b

AI summary

The invention relates to a method for identifying and quantifying by mass spectrometry at least one target molecule in a sample,comprising the following steps: a) depositing the sample to be analyzed on a support; b) analyzing the sample by mass spectrometry, so as to obtain the mass spectrum of the target molecule in said sample; c) weighting a signal associated with the mass spectrum of the target molecule in said sample by a extinction coefficient (TEC) specific to the target molecule and to the sample; and optionally d) using the weighted signal of the target molecule to determine the quantity of target molecule in the sample.