High Mass Accuracy Filtering for GC-MS Spectral Matching

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Solution Overview

Problem

Current gas chromatography mass spectrometry (GC-MS) methods face ambiguity in analyte identification due to the poor specificity of unit-resolution spectra, leading to false identifications, and the high cost of recreating high-resolution spectra libraries, while predictive fragmentation models often fail to match experimentally measured spectra accurately.

Innovation Solution

A method that uses high-resolution mass spectrometry to analyze data with unit-resolution spectral data, incorporating additional filtering and scoring steps to enable high-resolution matching with existing unit-resolution libraries, by converting high-resolution spectra to lower resolution and comparing them with calculated fragment masses for candidate molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If unit-resolution spectral data is used for matching, then compatibility with existing reference libraries is maintained, but identification specificity deteriorates leading to false identifications

Engineering Contradiction:
Improvecompatibility with existing reference librariesVSAvoididentification specificity
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent introduces a new dimension of analysis by applying high-resolution mass filtering to the traditional spectral matching process. Instead of relying solely on unit-resolution spectral patterns, the method adds accurate mass measurement as an additional filtering criterion, thereby maintaining compatibility with existing libraries while significantly improving identification specificity through multi-dimensional validation

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent changes the resolution parameter of mass spectrometry data from unit-resolution to high-resolution accurate mass measurements. By applying high-resolution mass filtering to both the query spectra and reference library spectra, the method transforms the matching process to operate on more precise mass values, thereby improving specificity while maintaining library compatibility

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If high-resolution mass spectrometry is used for analysis, then spectral matching specificity is improved, but the cost of recreating reference libraries increases prohibitively

Engineering Contradiction:
Improvespectral matching specificityVSAvoidcost of reference library recreation
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent creates a virtual high-resolution reference library by applying high-resolution mass filtering algorithms to existing unit-resolution reference spectra. Instead of physically recreating the library with high-resolution measurements, the method generates computationally-derived high-resolution representations of reference compounds, thereby achieving high-resolution matching capability without the prohibitive cost of experimental library recreation

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent introduces a computational intermediary layer that translates unit-resolution reference library data into high-resolution format through accurate mass filtering algorithms. This intermediary processing step allows the system to leverage existing low-cost unit-resolution libraries while achieving the analytical power of high-resolution mass spectrometry without direct high-resolution library measurements

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If predictive fragmentation models are used to generate theoretical spectra, then high-resolution matching can be achieved, but the accuracy of matching deteriorates due to poor correlation with experimental spectra

Engineering Contradiction:
Improvehigh-resolution matching capabilityVSAvoidspectral correlation accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies high-resolution mass filtering to experimental reference spectra to establish empirically-derived accurate mass patterns. These experimentally-grounded mass relationships serve as feedback criteria for validating candidate identifications, ensuring that theoretical matches are consistent with actual experimental observations rather than relying solely on predictive algorithms

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent performs preliminary high-resolution mass filtering on experimental reference spectra to extract accurate mass relationships before conducting the matching process. By pre-establishing experimentally-derived mass filters from reference compounds, the system prepares validation criteria in advance that are grounded in actual experimental data, improving the reliability of subsequent identifications

Inventive Principle:
Principle #10Preliminary action

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

This approach increases the specificity and confidence of compound identification by explaining a significant portion of the high-resolution mass spectra with calculated fragment masses, improving the accuracy of spectral matching without the need for new high-resolution libraries.

Implementation Method 1

measuring a fragmentation spectrum for said analyte using a mass spectrometry technique providing a mass accuracy equal to or less than 75 ppm

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 2

One typical ionization methods is electron ionization (EI) which causes molecules to fragment in reproducible patterns

Methodology Applied
Scientific EffectElectron ionization: Ionisation

Data Source

PatentEP3123495B1High mass accuracy filtering for improved spectral matching of high-resolution gas chromatography-mass spectrometry data against unit-resolution reference databases
Publication Date: 2019.11.13 WISCONSIN ALUMNI RES FOUND
  • EP3123495B1 patent drawingFigure 1
  • EP3123495B1 patent drawingFigure 2
  • EP3123495B1 patent drawingFigure 3A

AI summary

The invention provides methods, systems and algorithms for identifying high- resolution mass spectra. In some embodiments, an analyte is ionized and analyzed using high-resolution mass spectrometry (MS) at high mass accuracy (such as ≤ 75 ppm or ≤ 30 ppm) and the obtained mass spectra are matched with one or more prospective candidate molecules or chemical formulas. The invention provide, for example, methods and systems wherein the possible fragments that can be generated from the candidate molecules or chemical formulas are determined as well as the masses of each of these fragments. The invention provide, for example, methods and systems wherein the high-resolution mass spectra are then compared with the calculated fragment masses for each of the candidate molecules or chemical formula, and the portion of the high-resolution mass spectra that corresponds or can be explained by the calculated fragment masses is determined.