Atmospheric Pressure ECD Fragmentation for Mass Spectrometry

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Solution Overview

Problem

Current mass spectrometry techniques, such as AP-ECD, face challenges in associating precursor ions with their fragment ions due to complex spectra and the inability to select precursor ions before fragmentation, limiting analytical utility and commercial acceptance.

Innovation Solution

A method involving the creation of supercharged analyte ions, followed by charge transfer using electrons or reagent ions at atmospheric pressure, allowing for the isolation and excitation of intermediate ions to produce daughter ions, which can be analyzed to simplify the association of fragment ions with their precursors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If AP-ECD is used for dissociating ions, then dissociation can be achieved, but complex fragment ion spectra result making it difficult to associate precursor ions with their fragment ions

Engineering Contradiction:

Improvedissociation capabilityVSAvoidspectral complexity

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The invention segments the ion processing into distinct stages: first generating fragment ions through AP-ECD dissociation, then separately identifying precursor ions through liquid chromatography separation, and finally correlating the two through data processing. This segmentation allows each stage to be optimized independently while maintaining overall system reliability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention introduces liquid chromatography as an intermediary step between ion generation and fragmentation analysis. This intermediary separates mixture components in time, providing a temporal reference that facilitates correlation between precursor and fragment ions, thereby reducing spectral complexity while maintaining dissociation capability.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Loss of information

If liquid chromatography is used to separate components, then spectral complexity is reduced, but analysis time increases

Engineering Contradiction:

Improvespectral complexityVSAvoidanalysis time

Core Design Contradiction:

Loss of informationVSLoss of time

Solution Approach 1:

The invention applies partial action by using liquid chromatography separation only when analyzing mixtures of analytes, rather than for all samples. For single analyte samples, the full separation process can be bypassed, reducing analysis time while still providing spectral complexity reduction when needed.

Inventive Principle:

Principle #16Partial or excessive action

Solution Approach 2:

The invention maintains continuity by performing liquid chromatography separation continuously during sample introduction, with the separation process occurring in parallel with ion generation. This eliminates idle time between separation and analysis, reducing overall analysis time while maintaining the benefits of reduced spectral complexity.

Inventive Principle:

Principle #20Continuity of useful action

3Measurement precision

If conventional ECD or ETD MS/MS is used, then precursor ion selection is possible, but intermediate non-dissociated species are produced requiring additional ion activation

Engineering Contradiction:

Improveprecursor ion selectionVSAvoidion activation steps

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The invention replaces the mechanical precursor ion selection system (quadrupole mass filter) with a chemical/biological separation system (liquid chromatography). This substitution eliminates the need for complex ion activation steps because the chromatographic separation provides sufficient precursor identification without requiring precise mass selection and subsequent dissociation activation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 enables the identification of analyte ions by correlating intermediate ions with their daughter ions, simplifying the analysis of complex spectra and eliminating the need for low-pressure precursor ion selection, thus enhancing the analytical capability of mass spectrometry.

Implementation Method 1

supplying electrons or reagent ions to said analyte ions so as to transfer charge from said reagent ions or electrons to said analyte ions, said transfer of charge causing at least some of said analyte ions to dissociate

Methodology Applied

Scientific EffectCharge transfer:

Implementation Method 2

reacting all of the ion species generated by an electrospray ionisation (ESI) ion source with the photo-electrons from a UV lamp

Methodology Applied

Scientific EffectPhoto-electron generation: Photoelectric Effect

Data Source

PatentUS9892896B2MS/MS analysis using ECD or ETD fragmentation

Publication Date: 2018.02.13 MICROMASS UK LTD

AI summary

A method of mass spectrometry is disclosed comprising: providing supercharged analyte ions; and supplying electrons or reagent ions to said analyte ions so as to transfer charge from said reagent ions or electrons to said analyte ions, said transfer of charge causing at least some of said analyte ions to dissociate. The charge transfer step is performed at a relatively high pressure and preferably substantially at atmospheric pressure.