Reagent Ion Beam nETD for Sensitive Oligonucleotide Mass Spectrometry

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Conventional mass spectrometers utilizing negative electron transfer dissociation do not provide sufficient sensitivity for accurate interpretation of mass spectral data, especially for mass analysis of negatively charged large analytes like deprotonated oligonucleotides.

Innovation Solution

A method involving the use of a positively charged reagent ion beam generated via electron impact ionization, which interacts with negatively charged analyte ions in an ion trap to induce negative electron transfer dissociation, enhancing fragmentation efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional negative electron transfer dissociation is used in mass spectrometry, then the analysis of negatively charged analyte ions can be performed, but the sensitivity is insufficient for accurate interpretation of mass spectral data

Engineering Contradiction:

ImprovesensitivityVSAvoidaccuracy of mass spectral data interpretation

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent inverts the conventional ETD approach by using positively charged reagent ions instead of negative electrons to induce dissociation of negatively charged analyte ions. This inversion of charge polarity enables enhanced sensitivity and more efficient electron transfer reactions, directly addressing the insufficient sensitivity problem in conventional negative ETD while maintaining the ability to analyze negatively charged analytes.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent changes the charge state parameter of the reagent from negative (conventional electrons) to positive (reagent ions), which fundamentally alters the reaction dynamics and electron transfer efficiency. This parameter change enables better sensitivity and more reliable mass spectral data interpretation by creating more favorable reaction conditions for electron transfer dissociation.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If electron source is positioned to generate electrons for ETD, then electron transfer can occur, but electrons may inadvertently enter the ion trap and interfere with analyte ion analysis

Engineering Contradiction:

Improvereaction rate of negative electron transfer dissociationVSAvoidelectron interference in ion trap

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

Instead of using negative electrons that risk entering the ion trap, the patent inverts the approach by using positively charged reagent ions. This inversion naturally prevents the harmful effect of electron interference in the ion trap while maintaining high reaction rates through efficient electron transfer from the negatively charged analyte ions to the positive reagent ions.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent introduces positively charged reagent ions as an intermediary species that mediates the electron transfer process. These reagent ions serve as a safe intermediate that accepts electrons from analyte ions without causing the harmful interference that direct electron injection would cause, thereby enabling high productivity without harmful side effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 reaction rate of negative electron transfer dissociation, providing improved sensitivity and accuracy in mass spectral data interpretation for large analytes.

Implementation Method 1

accelerating the electrons to a kinetic energy sufficient for causing ionization of the reagent molecules, thereby generating a plurality of positively charged ions of the reagent molecules

Methodology Applied

Scientific EffectElectron impact ionization: Ionisation

Implementation Method 2

introducing and trapping the negatively charged analyte ions in an ion trap positioned in a chamber of the mass spectrometer

Methodology Applied

Scientific EffectElectrostatic trapping: Electrostatics

Implementation Method 3

the positively charged reagent ions enter the ion trap as an ion beam to interact with the negatively charged analyte ions so as to cause negative electron transfer dissociation (nETD) of at least a portion of the negatively charged analyte ions

Methodology Applied

Scientific EffectElectron transfer dissociation: Ionisation

Data Source

PatentUS20250323031A1Ion Beam Electron Transfer Dissociation

Publication Date: 2025.10.16 DH TECH DEVMENT PTE

AI summary

A method of dissociating an analyte in a mass spectrometer includes ionizing the analyte to generate a plurality of ions of the analyte, introducing and trapping the analyte ions into an ion trap, using an electron source to generate electrons, introducing a gas comprising a reagent molecule into a region between the electron source and a gate electrode, and using the gate electrode to cause ionization of the reagent molecules thereby generating a plurality of ions of the reagent molecule. The electron source inhibits entry of the accelerated electrons into the ion trap, the gate electrode is maintained at an electric potential to accelerate the reagent ions for entry into the ion trap as a positively charged ion beam, and the ion beam causes negative electron transfer dissociation of at least a portion of the analyte ions.