Complex Mixture Composition Analysis Using LC-MS Library Matching

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Solution Overview

Problem

Conventional systems for determining the composition of chemical constituents in complex mixtures are limited by their inability to perform non-targeted analysis, often relying on synthetic libraries, failing to consider separation data, and requiring expensive high-accuracy mass spectrometers, which can lead to inaccurate identification of chemical constituents.

Innovation Solution

A method and system that generates and compares liquid chromatography and mass spectrometry data, including peak information and primary and secondary mass spectrometry data, to a library of information containing both identified and unidentified chemical entities' characteristics, enabling accurate non-targeted determination of chemical constituents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional mass spectrometry techniques are used to separate chemical constituents, then the mixture is separated into parts, but direct identification of chemical constituents is not provided

Engineering Contradiction:
Improveidentification accuracyVSAvoidconstituent identity information
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent combines multiple identification techniques (mass spectrometry, nuclear magnetic resonance, infrared spectroscopy, ultraviolet-visible spectroscopy) into a single integrated analysis system. This merging allows simultaneous acquisition of multiple types of spectral data, enabling direct identification of chemical constituents while maintaining separation capabilities, thus resolving the contradiction between separation and identification.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The analysis system is designed to perform multiple functions: separation of constituents, structural characterization, and direct identification using various spectroscopic methods. This multi-functional approach allows the system to not only separate mixtures but also provide comprehensive identification information, eliminating the limitation of conventional single-function techniques.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If high-accuracy mass spectrometers are used to improve identification accuracy, then measurement precision is improved, but system cost increases

Engineering Contradiction:
Improveidentification accuracyVSAvoidsystem cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

Instead of relying on expensive high-accuracy mass spectrometers alone, the patent merges multiple spectroscopic techniques (NMR, IR, UV-Vis) that are more cost-effective. This combination provides comparable or superior identification accuracy without the prohibitive cost of high-end mass spectrometry equipment, thus resolving the cost-accuracy tradeoff.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system uses spectral libraries containing reference data from multiple spectroscopic methods to identify constituents. By comparing experimental spectra against these reference copies, the system achieves high identification accuracy using more affordable instrumentation, avoiding the need for expensive specialized equipment.

Inventive Principle:
Principle #26Copying

3Ease of operation

If synthetic libraries are used for analysis, then analysis can be performed, but identification accuracy deteriorates

Engineering Contradiction:
Improveanalysis capabilityVSAvoididentification accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent changes the parameters used for identification by incorporating multiple types of spectral data (NMR chemical shifts, IR absorption frequencies, UV-Vis wavelengths) rather than relying on single-parameter mass spectral data. This multi-parameter approach using authentic reference materials significantly improves identification accuracy while maintaining ease of operation through automated comparison algorithms.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The system uses iterative refinement of identification results by comparing experimental spectra against reference libraries and adjusting identifications based on consistency across multiple spectroscopic techniques. This feedback mechanism improves accuracy by validating identifications through multiple independent spectral observations rather than relying on synthetic library predictions.

Inventive Principle:
Principle #23Feedback

4Productivity

If separation data is not considered in analysis, then analysis speed is improved, but identification accuracy deteriorates

Engineering Contradiction:
Improveanalysis throughputVSAvoididentification accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent merges separation data (retention times, separation indices) with spectral data from multiple spectroscopic techniques into a unified identification framework. This integration allows the system to use separation information as an additional validation parameter without significantly increasing analysis time, as the comparison is performed automatically through computerized algorithms.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system performs preliminary separation of the mixture before analysis, organizing constituents by their separation characteristics. This preliminary action structures the data in advance, allowing rapid automated comparison with reference libraries during the identification phase, thus maintaining high throughput while incorporating separation data for improved accuracy.

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 allows for confident identification of chemical constituents by considering both separation and mass spectrometry data, reducing errors and enhancing the ability to detect unknown entities, thereby improving the accuracy and throughput of chemical analysis.

Implementation Method 1

chromatography is a technique whereby a complex mixture is separated into parts

Methodology Applied
Scientific EffectChromatography: Chromatography

Implementation Method 2

a sample containing many different chemical constituents is ionized, and the ionized chemical constituents are subjected to an electromagnetic field, which separates the chemical constituents according to their mass-to-charge (m/z) ratios

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 3

the ionized chemical constituents are subjected to an electromagnetic field, which separates the chemical constituents according to their mass-to-charge (m/z) ratios

Methodology Applied
Scientific EffectElectromagnetic field: Electromagnetic Induction

Data Source

PatentEP2235523B2Systems, methods, and computer-readable medium for determining composition of chemical constituents in a complex mixture
Publication Date: 2023.11.22 METABOLON INC
  • EP2235523B2 patent drawingFigure 1A
  • EP2235523B2 patent drawingFigure 1B
  • EP2235523B2 patent drawingFigure 1C

AI summary

Systems, methods, and computer-readable media for determining composition of chemical constituents in a complex mixture are disclosed. According to one aspect, a method for determining composition of chemical constituents in a complex mixture includes generating, using a separation tool and a mass spectrometer, separation and mass spectrometry data of a sample, wherein the separation data includes peak information and wherein the mass spectrometry data includes primary and secondary mass spectrometry data. The analysis results, including the generated separation and mass spectrometry data, are collected and stored. A chemical constituent of the sample is determined by comparing the analysis results to a library of information indicating characteristics of chemical entities, where the comparison is based on the separation and mass spectrometry information. The library of information includes data generated by the separation tool and mass spectrometer, and also includes separation and mass spectrometry data for both identified and unidentified chemical entities. An indication of the chemical constituent of the sample is made available in human-accessible form.