Mass Spectrometry Ion Alignment for Complex Sample Quantification

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Solution Overview

Problem

Conventional mass spectrometry techniques face challenges in accurately quantifying compounds in complex samples due to interference from multiple compounds co-eluting at the same retention time and detector saturation, leading to inadequate signal profiles.

Innovation Solution

A computer-implemented method aligns product ions with their parent precursor ions using mass information, specifically by comparing the rate of change of nominal and fractional mass, to segregate and identify ions more accurately.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional MS techniques are used to analyze complex samples, then the analysis can be performed with standard methods, but the accuracy of compound quantification deteriorates due to interference from co-eluting compounds and detector saturation

Engineering Contradiction:
Improveaccuracy of compound quantificationVSAvoidinterference from co-eluting compounds
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent segments the complex mass spectrum by aligning product ions with their parent precursor ions using mass defect and nominal mass comparisons. This segmentation separates ions from different compounds that co-elute at the same retention time, allowing individual quantification of each compound without interference from others in the mixture.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent uses mass defect and nominal mass as intermediary parameters to align and segregate product ions with their precursors. By comparing these mass characteristics, the method creates a reference framework that mediates the assignment of product ions to their correct parent compounds, even when multiple compounds are present at the same retention time.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If conventional MS techniques are used to analyze complex samples, then the analysis can be performed with standard equipment, but the correlation between peak area and compound concentration deteriorates due to detector saturation from high-abundance compounds

Engineering Contradiction:
Improvecorrelation between peak area and compound concentrationVSAvoiddetector saturation
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The patent segments the total ion signal by attributing product ions to specific precursor ions through mass alignment. This segmentation allows the quantification of individual compounds based on their aligned product ion intensities rather than total peak area, preventing saturation effects from high-abundance compounds from affecting the linearity of detection for lower-abundance compounds.

Inventive Principle:
Principle #1Segmentation

3Ease of operation

If product ions are not aligned with parent precursors, then the analysis is simpler, but the selectivity and accuracy of compound identification deteriorates

Engineering Contradiction:
Improvesimplicity of analysisVSAvoidselectivity and accuracy of compound identification
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent implements a self-service alignment mechanism where product ions automatically align with their parent precursors based on their inherent mass defect and nominal mass characteristics. The system uses the mass relationships inherent in the fragmentation process to self-correct and self-align ion assignments without requiring manual intervention or complex external calibration, thus maintaining ease of operation while improving accuracy.

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP3542292B1Techniques for mass analyzing a complex sample
Publication Date: 2024.09.11 WATERS TECHNOLOGY CORP
  • EP3542292B1 patent drawingFigure 1
  • EP3542292B1 patent drawingFigure 2
  • EP3542292B1 patent drawingFigure 3

AI summary

Techniques and apparatus for analyzing mass spectrometry data are described. In one embodiment, for example, an apparatus may include logic to access a product ion data set generated via mass analyzing a sample comprising a target precursor, access precursor composition information for elements of the target precursor that includes nominal mass and mass defect information, determine nominal mass (NM)-mass defect (MD) relationship information for ion fragments associated with the target precursor based on the precursor composition information, determine one or more fragment upper boundaries and one or more fragment lower boundaries, extract candidate ion fragments from the ion fragments via applying the one or more fragment upper boundaries and the one or more fragment lower boundaries to the NM-MD relationship information, and determine target ion fragments from the plurality of candidate ion fragments based on fragmentation efficiency information associated with the candidate ion fragments. Other embodiments are described and claimed.