Proton Transfer Reaction Charge Reduction for Mass Spectrometry

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Solution Overview

Problem

Mass spectrometers face difficulties in resolving multiply charged fragment ions produced by Electron Transfer Dissociation, as these ions have high charge states that are challenging to resolve due to their complex fragmentation patterns and the need for expensive and large Fourier Transform Ion Cyclotron Resonance mass analyzers.

Innovation Solution

A mass spectrometer with a Proton Transfer Reaction device that uses neutral, non-ionic superbase reagents to reduce the charge state of ions, specifically reacting protons with multiply charged analyte ions to lower their charge state, thereby improving spectral capacity and mass resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If Fourier Transform Ion Cyclotron Resonance mass analyzers are used to resolve multiply charged fragment ions, then mass resolution is improved, but device complexity and cost increase significantly

Engineering Contradiction:
Improvemass resolutionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by reducing the charge state of multiply charged ions before they enter the mass analyzer. The proton transfer reaction device performs charge reduction in advance, converting high-charge-state ions into lower-charge-state ions that can be resolved by simpler, less expensive mass analyzers, thereby avoiding the need for complex FT-ICR equipment

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent introduces an intermediary device - the proton transfer reaction device - that acts as a mediator between the ion source and the mass analyzer. This intermediary performs charge state reduction, enabling the mass analyzer to resolve ions that would otherwise require much more complex equipment, thus resolving the contradiction between measurement precision and device complexity

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If Fourier Transform Ion Cyclotron Resonance mass analyzers are used to resolve multiply charged fragment ions, then mass resolution is improved, but equipment cost increases significantly

Engineering Contradiction:
Improvemass resolutionVSAvoidequipment cost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

By performing charge state reduction beforehand in the proton transfer reaction device, the patent enables the use of less expensive mass analyzers that can still achieve adequate resolution for the reduced-charge ions, thereby reducing equipment cost while maintaining measurement precision

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The proton transfer reaction device serves as an intermediary that bridges the gap between simple mass analyzers and the need to resolve complex multiply charged ions, allowing cost-effective instrumentation to achieve high-resolution results through preliminary charge reduction

Inventive Principle:
Principle #24Intermediary (Mediator)

3Loss of information

If multiply charged fragment ions are produced by Electron Transfer Dissociation, then fragmentation information is improved, but spectral density decreases due to high charge states

Engineering Contradiction:
Improvefragmentation informationVSAvoidspectral density
Core Design Contradiction:
Loss of informationVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by reducing the charge state of fragment ions immediately after Electron Transfer Dissociation. This charge reduction transforms the spectral characteristics, increasing spectral density and making the fragmentation information more accessible and easier to analyze without losing the beneficial fragmentation patterns

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

The reduction of ion charge state enhances the mass spectrometer's ability to resolve ions, improving spectral density and simplifying mass spectral data, allowing for better identification of fragment ions without the need for expensive equipment.

Implementation Method 1

reacting first ions with one or more neutral, non-ionic or uncharged superbase reagent gases or vapours in order to reduce the charge state of the first ions

Methodology Applied
Scientific EffectProton Transfer Reaction: Chemical Bonding

Data Source

PatentUS10490394B2Method of charge reduction of electron transfer dissociation product ions
Publication Date: 2019.11.26 MICROMASS UK LTD
  • US10490394B2 patent drawing
  • US10490394B2 patent drawing
  • US10490394B2 patent drawing

AI summary

A mass spectrometer is disclosed wherein highly charged fragment ions resulting from Electron Transfer Dissociation fragmentation of parent ions are reduced in charge state within a Proton Transfer Reaction cell by reacting the fragment ions with a neutral superbase reagent gas such as Octahydropyrimidolazepine.