Hybrid Ion Pre-Separation for Narrow-Window Mass Spectrometry

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Solution Overview

Problem

Existing mass spectrometry techniques face challenges in balancing isolation width and precursor m/z range, leading to either lower quality data or decreased duty cycle due to narrow isolation windows filtering out a large number of precursor ions.

Innovation Solution

A system comprising a first pre-separation device for spatially separating precursor ions by mobility and a second pre-separation device for further separation by m/z, synchronized with a mass spectrometer to ensure the m/z range of each packet corresponds to the isolation window, improving duty cycle and sensitivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If narrower isolation windows are used, then data quality and sensitivity are improved, but the duty cycle decreases due to filtering out a large number of precursor ions

Engineering Contradiction:
Improvedata qualityVSAvoidduty cycle
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies preliminary action by performing ion mobility separation before mass spectrometry analysis. This pre-separation organizes precursor ions by mobility characteristics, allowing the subsequent narrow isolation window to efficiently capture relevant ions without losing too many precursor ions, thus maintaining both high data quality and acceptable duty cycle

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent segments the precursor ion population by separating ions based on their mobility characteristics into distinct groups. This segmentation allows the mass spectrometer to focus on specific ion subsets with narrow isolation windows, improving data quality while the systematic scanning approach ensures comprehensive coverage of all ion types over time, maintaining duty cycle

Inventive Principle:
Principle #1Segmentation

2Adaptability or versatility

If wider isolation widths are used, then the precursor m/z range and number of precursor ion species analyzed are increased, but data quality decreases due to co-isolation and co-fragmentation of neighboring analytes

Engineering Contradiction:
Improveprecursor m/z rangeVSAvoiddata quality
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary ion mobility separation to organize precursor ions by their mobility characteristics before they enter the mass spectrometer. This pre-organization allows the use of wider isolation widths to cover broader m/z ranges while the mobility-based pre-separation ensures that ions are systematically grouped, reducing random co-isolation of unrelated analytes and maintaining data quality

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces ion mobility as an additional separation dimension beyond the traditional m/z dimension. This creates a two-dimensional separation space where ions are first organized by mobility and then analyzed by m/z. The added dimension allows wider isolation widths to be used effectively because the mobility pre-separation has already organized the ion population, reducing co-fragmentation issues while expanding the analyzable m/z range

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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

The hybridized ion pre-separation method enhances the duty cycle and sensitivity of mass spectrometry by pre-separating precursor ions based on both mobility and m/z, allowing for smaller isolation windows and increased efficiency.

Implementation Method 1

a first pre-separation device configured to spatially separate precursor ions into a plurality of subsets of precursor ions according to mobilities of the precursor ions

Methodology Applied
Scientific EffectIon mobility separation: Electrophoresis

Implementation Method 2

a second pre-separation device configured to receive the plurality of subsets of precursor ions emitted from the first pre-separation device and, for each subset of precursor ions, sequentially emit a plurality of packets of precursor ions from the second pre-separation device based on a mass-to-charge ratio (m/z) of the precursor ions

Methodology Applied
Scientific EffectMass-to-charge ratio separation: Electromagnetic Induction

Data Source

PatentEP4672302A1Hybridized ion pre-separation for mass spectrometry
Publication Date: 2025.12.31 THERMO FINNIGAN LLC
  • EP4672302A1 patent drawingFigure 1
  • EP4672302A1 patent drawingFigure 2
  • EP4672302A1 patent drawingFigure 3

AI summary

A system includes a first pre-separation device configured to perform a first pre-separation of precursor ions according to mobilities of the precursor ions and a second pre-separation device positioned downstream of the first pre-separation device configured to perform a second pre-separation of precursor ions based on a mass-to-charge ratio (m/z) of the precursor ions. The system further includes a mass spectrometer positioned downstream of the second pre-separation device configured to acquire mass spectra for precursor ions emitted from the second pre-separation device. The second pre-separation device is synchronized with the mass spectrometer such that an m/z range of precursor ions emitted from the second pre-separation device corresponds to a precursor m/z isolation window of the mass spectrometer.