Dynamic Dissociation Selection in Mass Spectrometry

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Solution Overview

Problem

Existing data-dependent acquisition methods in mass spectrometry are limited to using a single conventional dissociation mode, failing to fully exploit the capabilities of advanced dissociation techniques for peptides and biomolecules analysis.

Innovation Solution

The method involves selecting a dissociation type based on the charge state of ion species, using a list of candidate dissociation types such as CAD, PQD, ECD, ETD, and ETD followed by supplemental reactions, to produce product ions and acquire MS/MS spectra, allowing for more effective data acquisition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If a single conventional dissociation mode is used in data-dependent acquisition, then the method is simple to implement, but the informational content of the mass spectrometric data is limited

Engineering Contradiction:
Improveinformational content of mass spectrometric dataVSAvoidcomplexity of data-dependent acquisition method
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The system dynamically selects the dissociation type (CAD, ETD, ECD, PQD) based on real-time analysis of ion charge state and other parameters from the mass spectrum. This dynamic adaptation allows the system to optimize information extraction for each ion species while maintaining automated operation, resolving the contradiction between information content and method complexity

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The invention changes the operational parameters of the mass spectrometer by selecting different dissociation types based on ion characteristics such as charge state. By adjusting the dissociation method parameter according to the detected ion properties, the system maximizes the informational content obtained from each ion species without requiring manual intervention

Inventive Principle:
Principle #35Parameter changes

2Loss of information

If advanced dissociation techniques are introduced to enhance data quality, then the informational content improves, but the existing data-dependent acquisition methods cannot effectively utilize them

Engineering Contradiction:
Improveinformational content of mass spectrometric dataVSAvoidcompatibility of data-dependent acquisition with dissociation techniques
Core Design Contradiction:
Loss of informationVSAdaptability or versatility

Solution Approach 1:

The data-dependent acquisition system is designed to be universal by supporting multiple dissociation techniques (CAD, ETD, ECD, PQD) within a single automated framework. The system evaluates ion characteristics and selects the most appropriate dissociation method from the available options, making the acquisition method adaptable to various ion types and enabling effective utilization of advanced dissociation techniques

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system dynamically adapts to different ion species by selecting the most suitable dissociation technique based on real-time analysis of mass spectrum data. This dynamic selection capability enables the system to effectively utilize multiple advanced dissociation techniques while maintaining automated operation, thereby improving adaptability without sacrificing data quality

Inventive Principle:
Principle #15Dynamics

3Loss of information

If multiple chromatographic runs are performed to maximize useful information, then the information content increases, but the analysis time and productivity decrease

Engineering Contradiction:
Improveuseful information content of acquired dataVSAvoidanalysis throughput
Core Design Contradiction:
Loss of informationVSProductivity

Solution Approach 1:

The system performs preliminary analysis of the mass spectrum to identify ion species of interest and pre-determines the optimal dissociation type for each identified ion before actual MS/MS acquisition. This preliminary action allows the system to maximize information extraction in a single run by making informed real-time decisions, eliminating the need for multiple chromatographic runs and thereby maintaining high productivity

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 informational content of mass spectrometric data by tailoring dissociation techniques to ion charge state, improving data quality and efficiency in analyzing complex samples.

Implementation Method 1

a mass analyzer for acquiring a mass spectrum of the ions

Methodology Applied
Scientific EffectMass analysis:

Implementation Method 2

collisionally activated dissociation (CAD)

Methodology Applied
Scientific EffectCollisionally activated dissociation:

Implementation Method 3

pulsed-q dissociation (PQD)

Methodology Applied
Scientific EffectPulsed-q dissociation:

Implementation Method 4

electron capture dissociation (ECD)

Methodology Applied
Scientific EffectElectron capture dissociation:

Implementation Method 5

electron transfer dissociation (ETD)

Methodology Applied
Scientific EffectElectron transfer dissociation:

Implementation Method 6

photodissociation

Methodology Applied
Scientific EffectPhotodissociation: Photodissociation

Data Source

PatentEP2062284B1Data-dependent selection of dissociation type in a mass spectrometer
Publication Date: 2018.08.15 THERMO FINNIGAN LLC
  • EP2062284B1 patent drawingFigure 1
  • EP2062284B1 patent drawingFigure 2
  • EP2062284B1 patent drawingFigure 3~4

AI summary

Methods and apparatus for data-dependent mass spectrometric MS/MS or MSn analysis are disclosed. The methods may include determination of the charge state of an ion species of interest, followed by automated selection of a dissociation type (e.g., CAD, ETD, or ETD followed by a non-dissociative charge reduction or collisional activation) based at least partially on the determined charge state. The ion species of interest is then dissociated in accordance with the selected dissociation type, and an MS/MS or MSn spectrum of the resultant product ions may be acquired.