Multi-Ionization Chemical Tags for Isobaric Species Separation

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Solution Overview

Problem

Current methods for analyzing complex biological samples, such as shotgun lipidomics, struggle to accurately distinguish and quantify isobaric species due to chemical complexity, leading to inefficiencies in separation and identification of components.

Innovation Solution

The use of chemical tags with two or more ionization sites to selectively react with sample components, followed by separation based on charge state using ion mobility spectrometry or capillary electrophoresis, and subsequent characterization of components.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional analytical methods such as mass spectrometry analysis of complex mixtures are used, then analysis can be performed on biological samples, but accurate results cannot be delivered due to chemical complexity and inability to distinguish isobaric species

Engineering Contradiction:
Improveaccuracy of component identificationVSAvoidchemical complexity of sample
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent divides the complex mixture into separate components by tagging specific molecules with chemical probes that have multiple ionization sites. This segmentation allows multiply-charged tagged components to be separated from other components based on charge state, resolving the inability to distinguish isobaric species in complex mixtures

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces chemical tags with multiple ionization sites as intermediary substances that selectively react with target components. These tags serve as mediators that enable differentiation of isobaric species by creating multiply-charged ions that can be separated and identified more accurately

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If chemical modifiers are used to label specific molecules, then visualization of particular components is improved, but separation and characterization of components from complex samples cannot be achieved

Engineering Contradiction:
Improvevisualization capabilityVSAvoidseparation capability
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent changes the charge state parameter of tagged components by using chemical tags with multiple ionization sites. This parameter change enables separation based on charge state, as multiply-charged tagged components behave differently during separation processes compared to singly-charged or untagged components

Inventive Principle:
Principle #35Parameter changes

3Productivity

If shotgun lipidomics is used to analyze biological samples, then component analysis can be performed, but isobaric species cannot be distinguished and quantified accurately

Engineering Contradiction:
Improveanalysis throughputVSAvoiddistinguishment of isobaric species
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary tagging of target components with chemical probes before the main analysis process. This preliminary action of introducing multiple ionization sites onto specific molecules enables subsequent accurate distinction and quantification of isobaric species during mass spectrometry analysis

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 enhances the resolution and accuracy of component separation, allowing for rapid analysis with minimal sample preparation, improved selectivity, sensitivity, and specificity, and enables spatial localization of biological molecules.

Implementation Method 1

chemical tags which have two or more sites for ionization to improve quantification, identification and/or spatial localization of components of interest from a complex mixture

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

separating the components using ion mobility spectrometry or capillary electrophoresis

Methodology Applied
Scientific EffectIon mobility: Electrophoresis

Implementation Method 3

separating the components using ion mobility spectrometry or capillary electrophoresis

Methodology Applied
Scientific EffectElectrophoresis: Electrophoresis

Data Source

PatentEP3417282B1Chemical tags and their use for identification, quantification and spatial localization of components in a sample
Publication Date: 2026.04.15 WATERS TECHNOLOGY CORP
  • EP3417282B1 patent drawingFigure 1
  • EP3417282B1 patent drawingFigure 2
  • EP3417282B1 patent drawing

AI summary

The present disclosure relates to a method for using chemical tags which have two or more sites for ionization to improve quantification and identification of components of interest from a complex mixture. This method relies on first selectively reacting one or more component in a sample with a chemical tag having two or more sites for ionization, followed by separation of components based on charge status, and finally characterization of each component to identify the same. Additionally disclosed are compounds useful as chemical tags in the disclosed methods.