Tandem Mass Spectrometry Variable Window Segmentation

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Solution Overview

Problem

Traditional rapid sample analysis methods, such as coupling fast separation techniques with high resolution mass spectrometry, often fail to reveal subtle differences between samples due to complications like ion suppression, unresolved isomers, matrix effects, or isobaric species, limiting their ability to detect important molecular variations.

Innovation Solution

A non-chromatographic fast sample introduction technique is combined with tandem mass spectrometry, using variable mass selection window widths across the mass range to improve both specificity and sensitivity, allowing for fragmentation scans that reveal complexities in sample data, including differences between isomers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Speed

If fast separation techniques are coupled with high resolution mass spectrometry to achieve rapid sample analysis, then analysis speed is improved, but subtle molecular differences are lost due to ion suppression, unresolved isomers, matrix effects, or isobaric species

Engineering Contradiction:
Improveanalysis speedVSAvoiddetection of subtle molecular differences
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The mass spectrum is segmented into multiple isolation windows across the mass range, allowing selective isolation and fragmentation of specific mass-to-charge ratio ranges. This segmentation enables targeted analysis that resolves isomers and distinguishes subtle molecular differences while maintaining rapid throughput.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system dynamically adjusts the isolation window width and position across different mass ranges, using narrower windows for regions with isobaric species and wider windows for regions with fewer interferences. This dynamic adaptation optimizes both specificity and sensitivity throughout the analysis.

Inventive Principle:
Principle #15Dynamics

2Measurement precision

If traditional mass spectrometry methods are used to maintain high resolution, then measurement precision is improved, but analysis throughput decreases due to time-consuming separation techniques

Engineering Contradiction:
Improvemass resolutionVSAvoidsample throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

A fast sample introduction method is used to pre-separate or pre-concentrate analytes before mass spectrometry analysis, reducing the time required during the actual MS measurement. This preliminary action enables rapid sequential analysis of multiple samples while maintaining detection sensitivity.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system performs rapid full-scan mass spectrometry to identify all ions of interest, then quickly focuses on and fragments only the selected precursor ions. This skipping approach avoids time-consuming comprehensive separation while still achieving high-resolution analysis of target compounds.

Inventive Principle:
Principle #21Skipping (Rushing through)

3Measurement precision

If narrow mass selection window widths are used to improve specificity for detecting isobaric species, then measurement precision is improved, but the time required to scan the entire mass range increases

Engineering Contradiction:
Improvespecificity for isobaric speciesVSAvoidscan time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The mass range is divided into multiple overlapping isolation windows that are scanned sequentially. This segmentation allows narrow windows to be used for specific regions containing isobaric species while wider windows cover regions with fewer interferences, optimizing both specificity and scan speed.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system uses periodic full-scan surveys to identify precursor ions, followed by targeted fragmentation scans of selected mass windows. This periodic alternation between broad screening and focused analysis reduces total scan time while maintaining high specificity for detecting isobaric species.

Inventive Principle:
Principle #19Periodic 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 enables rapid and meaningful analysis of samples by reducing the impact of complications like ion suppression and saturation, providing high throughput and sensitivity while maintaining specificity, allowing for the detection of subtle differences and complexities in molecular structures.

Implementation Method 1

tandem mass spectrometry, using variable mass selection window widths across the mass range

Methodology Applied
Scientific EffectMass spectrometry:

Implementation Method 2

complications like ion suppression, unresolved isomers, matrix effects, or isobaric species

Methodology Applied
Scientific EffectIon suppression:

Data Source

PatentEP2638563B1Systems and methods for rapidly screening samples by mass spectrometry
Publication Date: 2022.10.05 DH TECH DEVMENT PTE
  • EP2638563B1 patent drawingFigure 1
  • EP2638563B1 patent drawingFigure 2
  • EP2638563B1 patent drawingFigure 3

AI summary

Systems and methods are used to rapidly screening samples. A fast sample introduction device that is non-chromatographic is instructed to supply each sample of a plurality samples to a tandem mass spectrometer using a processor. The fast sample introduction device can include a flow injection analysis device, an ion mobility analysis device, or a rapid sample cleanup device. The tandem mass spectrometer is instructed to perform fragmentation scans at two or more mass selection windows across a mass range of each sample of the plurality of samples using the processor. The two or more mass selection windows across the mass range can have fixed or variable window widths. The tandem mass spectrometer can be instructed to obtain a mass spectrum of the mass range before instructing the tandem mass spectrometer to perform the fragmentation scans.