Alternating Charge Reduction and Fragmentation Modes in Mass Spectrometry

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Solution Overview

Problem

Existing mass spectrometry techniques face challenges in efficiently correlating parent ions with their corresponding fragment ions due to overlapping species with different charge states, leading to complex spectral data and interference.

Innovation Solution

A method that alternates between charge reduction and fragmentation modes to maintain high charge states for parent ions, allowing for easier identification and association with fragment ions by reducing charge prior to mass analysis but not during fragmentation, and using different fragmentation techniques to produce distinct sets of fragment ions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If charge reduction is performed on parent ions before mass analysis, then spectral complexity is reduced and overlapping peaks are separated, but fragmentation efficiency decreases when parent ions are subsequently fragmented

Engineering Contradiction:
Improvemass spectral data qualityVSAvoidfragmentation efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The mass spectrometer alternates between two operational modes in a periodic cycle: a first mode for charge reduction and parent ion mass analysis, and a second mode for fragmentation and fragment ion mass analysis. This periodic switching allows the system to optimize for measurement precision during charge reduction phases while maintaining productivity during fragmentation phases, resolving the contradiction between these two requirements.

Inventive Principle:
Principle #19Periodic action

2Quantity of substance

If different species of parent ions with different charge states are analyzed simultaneously, then comprehensive mass spectral data is obtained, but spectral complexity increases and interference occurs

Engineering Contradiction:
Improveparent ion detection coverageVSAvoidspectral data complexity
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention extracts and removes the charge state variable from the mass spectral analysis by performing charge reduction on all parent ions before mass analysis. This separates the charge state parameter from the mass-to-charge ratio measurement, allowing different species of parent ions to be analyzed without their charge states causing spectral overlap or complexity. The charge reduction step isolates the mass analysis from charge state variations.

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If charge reduction conditions are optimized for parent ion analysis, then mass spectral data quality improves, but fragmentation capability is reduced

Engineering Contradiction:
Improveparent ion mass analysis accuracyVSAvoidfragmentation capability
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The mass spectrometer dynamically switches between two operational configurations: one optimized for charge reduction and parent ion analysis, and another optimized for fragmentation. By making the system dynamic and mode-switchable rather than static, it can adapt to different analytical requirements at different times, maintaining both high measurement precision for parent ions and effective fragmentation capability without compromise.

Inventive Principle:
Principle #15Dynamics

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 simplifies the association of parent and fragment ions, reduces spectral complexity, and increases the information content of mass spectral data, enhancing the identification of analytes, especially in complex mixtures like protein digests, by separating overlapping peaks and improving fragmentation efficiency.

Implementation Method 1

the charge reducing means for reducing the charge state of the parent ions by exposing the ions to charge reduction conditions

Methodology Applied
Scientific EffectCharge reduction:

Implementation Method 2

The fragmentation process may be Electron Transfer Dissociation ('ETD'), Electron Capture Dissociation ('ECD') or Collision Induced Dissociation ('CID')

Methodology Applied
Scientific EffectElectron Transfer Dissociation (ETD):

Implementation Method 3

The fragmentation process may be Electron Transfer Dissociation ('ETD'), Electron Capture Dissociation ('ECD') or Collision Induced Dissociation ('CID')

Methodology Applied
Scientific EffectCollision Induced Dissociation (CID):

Implementation Method 4

mass analysing the fragment ions to obtain second mass spectral data

Methodology Applied
Scientific EffectMass analysis:

Data Source

PatentEP2893550B1IMPROVED METHOD OF MSe MASS SPECTROMETRY
Publication Date: 2019.11.06 MICROMASS UK LTD
  • EP2893550B1 patent drawingFigure 1A~1C
  • EP2893550B1 patent drawingFigure 2

AI summary

A method of mass spectrometry is disclosed comprising alternating between a first mode in which parent ions are analysed and a second mode in which parent ions are fragmented and their fragment ions are mass analysed. In the first mode the parent ions are charge reduced before being analysed, so as to simplify the parent ion spectral data obtained. In the second mode, the parent ions are not charge reduced prior to fragmentation, so that it remains relatively easy to induce the parent ions to fragment. The parent ions are then associated with their fragment ions using the mass spectral data obtained.