Mass Labels with Fragmentable Marker Moieties for MS Analysis

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Solution Overview

Problem

Current mass spectrometry-based detection systems face limitations in analyzing multiple analytes simultaneously due to peak overlap, ion suppression, and the need for complex sample preparation, particularly when using isotope-coded affinity tags, which can lead to increased spectral complexity and reduced sensitivity.

Innovation Solution

A set of mass labels comprising a mass marker moiety attached via a cleavable linker to a mass normalization moiety, where the mass marker moiety can be fragmented into distinct fragments, allowing for the differentiation of multiple labels with the same overall mass, and isotopic labeling is used to create groups of chemically identical mass labels with varying fragment masses, enabling triple mass spectrometry analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If isotope-coded affinity tags are used for mass spectrometry-based detection, then the ability to analyze multiple analytes simultaneously is improved, but spectral complexity increases and sensitivity decreases due to peak overlap and ion suppression

Engineering Contradiction:

Improvenumber of analytes analyzed simultaneouslyVSAvoiddetection sensitivity

Core Design Contradiction:

Quantity of substanceVSMeasurement precision

Solution Approach 1:

The mass label is segmented into two distinct moieties: a mass marker moiety that fragments into diagnostic ions for identification, and a mass normalization moiety that provides a predictable mass contribution. This segmentation allows multiple labels with the same overall mass to be distinguished through their unique fragmentation patterns, resolving peak overlap issues

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The mass marker moiety acts as an intermediary that provides diagnostic fragmentation information. When the mass label fragments, the mass marker produces characteristic fragment ions that serve as fingerprints for identifying which specific label is present, enabling differentiation without requiring the entire label to have unique mass

Inventive Principle:

Principle #24Intermediary (Mediator)

2Quantity of substance

If isotope-coded affinity tags are used for mass spectrometry-based detection, then the ability to analyze multiple analytes simultaneously is improved, but peak overlap increases reducing analysis reliability

Engineering Contradiction:

Improvenumber of analytes analyzed simultaneouslyVSAvoiddetection reliability

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different regions of the mass label have different functional properties: the mass marker moiety is designed to fragment and provide diagnostic information, while the mass normalization moiety provides stable mass contribution. This local differentiation of function allows the system to maintain both identifiability and quantitative accuracy

Inventive Principle:

Principle #3Local quality

3Measurement precision

If complex sample preparation is used to reduce spectral complexity, then measurement precision is improved, but analysis time increases

Engineering Contradiction:

Improvedetection precisionVSAvoidsample preparation time

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The mass label structure enables self-identification through its own fragmentation pattern. The mass marker moiety automatically provides diagnostic fragment ions that identify the label type, eliminating the need for external reference standards or complex sample preparation steps to reduce spectral complexity

Inventive Principle:

Principle #25Self-service

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 the analysis of large numbers of unique labels, improved signal-to-noise ratios, and reduced sample complexity, enabling the detection of analytes in a background of contamination and enhancing the throughput and sensitivity of biomolecule analysis.

Implementation Method 1

the mass marker moiety is capable of fragmentation into two or more fragments

Methodology Applied

Scientific EffectCollision-induced dissociation:

Implementation Method 2

detectable by mass spectrometry

Methodology Applied

Scientific EffectMass spectrometry:

Data Source

PatentUS8946129B2Mass labels

Publication Date: 2015.02.03 ELECTROPHORETICS LTD

AI summary

Provided is a set of mass labels, each mass label in the set comprising a mass marker moiety attached via a cleavable linker to a mass normalization moiety, each mass label in the set having a common mass; wherein the set comprises a plurality of groups of mass labels, the mass of the mass marker moiety being the same for mass labels within a group, the mass of the mass marker moiety being different between groups; the mass marker moiety is capable of fragmentation into two or three fragments; and the mass of at least one fragment of the mass marker moiety differs between mass labels within a group.