Reagent for mass spectrometry

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Solution Overview

Problem

Existing mass spectrometry (MS) methods lack sensitivity for analyzing low-abundance carbohydrates and are prone to ion suppression by contaminants, making quantitative analysis challenging, especially in limited sample quantities like biopsy tissues.

Innovation Solution

A novel reagent with a reactive group capable of forming a covalent bond with analyte molecules, combined with a neutral ion loss unit that fragments under MS conditions and a charge unit, allowing for sensitive and quantitative analysis of carbohydrates.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional mass spectrometry methods are used for carbohydrate analysis, then the analysis can be performed with existing techniques, but the sensitivity is insufficient for low-abundance carbohydrates and quantitative accuracy is compromised by ion suppression

Engineering Contradiction:
Improvequantitative accuracyVSAvoidion suppression by contaminants
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces a derivatization reagent as an intermediary substance that chemically modifies carbohydrates to attach permanent charge units. This mediator enables the carbohydrates to ionize efficiently in mass spectrometry without being affected by ion suppression from contaminants, thereby achieving accurate quantitative analysis.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the chemical parameter of carbohydrates by derivatizing them with reagents containing permanent charge units (such as quaternary ammonium groups). This parameter change transforms neutral or weakly ionizing carbohydrates into highly ionizable derivatives, dramatically improving detection sensitivity and quantitative accuracy in mass spectrometry.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If conventional mass spectrometry is used without derivatization, then the sample preparation is simpler, but the sensitivity is too low for analyzing low-abundance carbohydrates in limited samples

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample preparation complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies preliminary derivatization action to carbohydrates before mass spectrometry analysis. By pre-attaching permanent charge units through chemical derivatization, the carbohydrates are prepared in advance to ensure high ionization efficiency and detection sensitivity, enabling analysis of low-abundance species in limited samples.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If MS signal intensity is used directly for quantification, then the measurement process is straightforward, but the results are inaccurate due to ionization properties and ion suppression effects

Engineering Contradiction:
Improvequantitative accuracyVSAvoidquantification simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent changes the ionization parameter of carbohydrates by attaching permanent charge units through derivatization. This ensures that signal intensity directly reflects the amount of analyte rather than ionization efficiency variations, enabling accurate quantification while maintaining operational simplicity.

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

The reagent enables extremely sensitive and quantitative determination of glycostructures, providing accurate MS data for comparative studies, particularly in biological samples with low abundance analytes.

Implementation Method 1

a reactive group X capable of reacting with an analyte molecule, whereby a covalent bond with the analyte molecule is formed

Methodology Applied
Scientific EffectCovalent bonding: Chemical Bonding

Implementation Method 2

a neutral ion loss unit Y which itself is neutral, and, under conditions of mass spectrometry, is capable of fragmentation, whereby a neutral species, particularly a low-molecular weight neutral species is released

Methodology Applied
Scientific EffectFragmentation:

Implementation Method 3

a charge unit Z comprising or consisting of (i) at least one positively charged moiety having a pKa of 10 or higher, or (ii) at least one negatively charged moiety having a pKb of 10 or higher

Methodology Applied
Scientific EffectIonization: Ionisation

Data Source

PatentEP3577466B1Reagent for mass spectrometry
Publication Date: 2026.01.07 F HOFFMANN LA ROCHE & CO AG
  • EP3577466B1 patent drawingFigure 1
  • EP3577466B1 patent drawingFigure 2
  • EP3577466B1 patent drawingFigure 3a~3c

AI summary

The present invention relates to reagents suitable in the mass spectrometric determination of analyte molecules such as carbohydrates as well as adducts of such reagents and analyte molecules and applications of said reagents and adducts. Further, the present invention relates to methods for the mass spectrometric determination of analyte molecules.