Ion Mobility Mass Spectrometry for Reduced Fragment Spectral Congestion

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Solution Overview

Problem

Spectral congestion in mass spectrometry analysis due to overlapping isotopic distributions of fragment ions with similar mass-to-charge ratios hinders efficient data interpretation, particularly in the analysis of intact proteins, polypeptide chains, and protein complexes.

Innovation Solution

An ion mobility drift cell with a buffer gas and a homogeneous electric field separates ions based on their mobility, allowing spatial separation and individual trapping of ions with the same mass-to-charge ratio, followed by mass analysis using a combination of RF and DC electric fields to generate fractional mass-to-charge spectra.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a single ion mobility spectrometer stage is used to separate ions, then ion separation based on mobility is achieved, but spectral congestion remains when fragment ions have comparable mass-to-charge ratios

Engineering Contradiction:
Improveion separation capabilityVSAvoidspectral congestion
Core Design Contradiction:
Measurement precisionVSLoss of information

Solution Approach 1:

The patent applies segmentation by dividing the ion analysis process into multiple sequential ion mobility spectrometer stages. Each stage separates ions based on their mobility characteristics, and the combination of multiple stages provides enhanced separation resolution. This allows fragment ions with comparable mass-to-charge ratios to be resolved into distinct mobility-based fractions, reducing spectral congestion while maintaining separation precision.

Inventive Principle:
Principle #1Segmentation

2Loss of information

If multiple ion mobility spectrometer stages are combined to reduce spectral congestion, then ion separation is improved, but device complexity increases

Engineering Contradiction:
Improvespectral congestion reductionVSAvoidnumber of spectrometer stages
Core Design Contradiction:
Loss of informationVSDevice complexity

Solution Approach 1:

The patent implements multi-functionality by designing each ion mobility spectrometer stage to perform both separation and fractionation functions. The stages are configured to work in sequence, with each stage contributing to the overall separation while also enabling independent control of ion fractions. This universal design allows the system to reduce spectral congestion through multiple stages without proportionally increasing complexity, as each component serves multiple purposes in the analysis workflow.

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

3Productivity

If fragment ions are analyzed directly without ion mobility separation, then analysis speed is maintained, but isotopic distributions overlap and cannot be distinguished

Engineering Contradiction:
Improveanalysis speedVSAvoidisotopic distribution resolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies preliminary action by performing ion mobility separation before mass analysis. The ion mobility spectrometer stages pre-separate fragment ions based on their mobility characteristics, organizing them into distinct fractions before they enter the mass analyzer. This preliminary separation ensures that when ions are subsequently analyzed by mass-to-charge ratio, their isotopic distributions remain resolved and distinguishable, maintaining measurement precision while enabling efficient analysis through the streamlined workflow.

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 method significantly reduces spectral density, simplifies complex spectra, and improves peak assignment, enabling de-novo sequencing of proteins by separating and analyzing fragment ions according to their charge states and shapes, reducing spectral congestion and enhancing data interpretation.

Implementation Method 1

The velocity v d with which an ion drifts through a buffer gas in response to a uniform applied electric field E, is determined by ion mobility K of the ion in the form: v d = KE

Methodology Applied
Scientific EffectIon mobility: Electrophoresis

Implementation Method 2

a homogeneous (e.g. DC) electrical field is applied to impose a drift force to ions in the drift cell in a direction along the longitudinal axis of the drift cell

Methodology Applied
Scientific EffectElectric field: Electric Field

Data Source

PatentEP3570312B1Mass spectrometer for analysing fragment ions and corresponding method
Publication Date: 2025.03.26 FASMATECH SCI & TECH SA
  • EP3570312B1 patent drawingFigure 1
  • EP3570312B1 patent drawingFigure 2
  • EP3570312B1 patent drawingFigure 3

AI summary

A mass spectrometer for analysing fragment ions, the mass spectrometer comprising an ion source for producing fragment ions, an ion mobility spectrometer for receiving fragment ions produced by the ion source and for separating at least a fraction of the received fragment ions according to their ion mobility into mobility-separated fragment ions. A system of electrodes is configured to receive DC electrical potentials to transfer at least a fraction of the mobility-separated fragment ions to a mass analyser for generating a mass-to-charge (m/z) spectrum exhibiting reduced spectral complexity.