Plasma-Based ECD Apparatus for High-Throughput Mass Spectrometry

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Solution Overview

Problem

Conventional electron sources for electron capture dissociation (ECD) in mass spectrometry suffer from low efficiency and high heat load, producing low-density low-energy electrons, which limits the throughput and compatibility with modern chromatographic separations.

Innovation Solution

A plasma-based ECD apparatus that generates and refines plasma to produce high-density low-energy electrons, filtering out unwanted plasma species to optimize electron density and energy for efficient fragmentation, using a plasma source and refinement device to create a refined plasma with predominantly low-energy electrons for ECD.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If heated cathode filaments are used as electron source, then electron emission current is increased, but heat load on the system and surrounding components is excessively high

Engineering Contradiction:
Improveelectron emission currentVSAvoidheat load
Core Design Contradiction:
Quantity of substanceVSTemperature

Solution Approach 1:

The patent replaces the thermal field-based electron emission mechanism (heated cathode filaments) with a field emission mechanism using cold cathode structures. This substitution eliminates the need for high-temperature heating while maintaining high electron emission currents through strong electric fields at sharp electrode tips, directly resolving the contradiction between electron current and heat load.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If heated cathode filaments are used, then electron beam intensity is increased, but the extracted electrons have high energy which is unsuitable for ECD

Engineering Contradiction:
Improveelectron beam intensityVSAvoidelectron energy
Core Design Contradiction:
Quantity of substanceVSUse of energy by moving object

Solution Approach 1:

The patent changes the fundamental operating parameters of the electron source by transitioning from thermal emission to field emission. This parameter change enables the generation of intense electron beams with low energy (suitable for ECD) by using high electric fields at cold cathode surfaces rather than thermal energy, simultaneously achieving high intensity and appropriate energy levels.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If space-charge limit is reached for low electron energies, then electron density is low, but this requires very long interaction distances and times reducing throughput

Engineering Contradiction:
Improveelectron densityVSAvoidthroughput
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The patent replaces the thermionic emission system with a field emission system using cold cathodes. This substitution overcomes the space-charge limit constraint because field emission can generate extremely high electron densities directly at the cathode surface through quantum tunneling effects, providing sufficient electron density for high-throughput ECD without requiring long interaction distances.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Device complexity

If conventional electron sources are used, then ECD process is simple, but efficiency is low and incompatible with modern chromatographic separations

Engineering Contradiction:
ImproveECD process simplicityVSAvoidanalysis throughput
Core Design Contradiction:
Device complexityVSProductivity

Solution Approach 1:

The patent replaces conventional heated cathode electron sources with cold cathode field emission sources. This substitution maintains the simplicity of the ECD process while dramatically increasing electron emission efficiency and throughput, making the system compatible with modern high-speed chromatographic separations by enabling faster analysis rates without complex additional components.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

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 significantly enhances ECD efficiency, allowing for high-throughput analysis of large molecules like peptides and proteins with improved fragmentation patterns and reduced heat load on the system.

Implementation Method 1

A plasma-based ECD apparatus that generates and refines plasma

Methodology Applied
Scientific EffectPlasma generation: Plasma

Implementation Method 2

converting the generated plasma to refined plasma comprising predominantly low-energy electrons suitable for ECD and plasma ions, filtering out unwanted plasma species

Methodology Applied
Scientific EffectPlasma refinement: Filter (physical)

Implementation Method 3

If their energy is low enough (typically less than 3 eV), the electrons can be captured by the positively charged sites on the ions. The energy released in the exothermic capture process is released as internal energy in the ion, which can then very quickly cause bond cleavage

Methodology Applied
Scientific EffectElectron capture dissociation: Electron Impact Desorption

Data Source

PatentEP2871665B1Plasma-based electron capture dissociation (ecd) apparatus and related systems and methods
Publication Date: 2016.05.25 AGILENT TECHNOLOGIES INC
  • EP2871665B1 patent drawingFigure 1
  • EP2871665B1 patent drawingFigure 2
  • EP2871665B1 patent drawingFigure 3

AI summary

An electron capture dissociation (ECD) apparatus (100; 200; 400; 500; 600; 806; 906; 1006; 1106, 1206; 1306) includes a plasma source (102; 202; 402; 502) for generating plasma. Analyte ions are exposed to the plasma in an ECD interaction region (110; 210; 410; 510), either inside or outside the plasma source. The apparatus may include one or more devices for refining the plasma in preparation for interaction with the analyte ions. Refining may entail removing unwanted species from the plasma, such as photons, metastable particles, neutral particles, and/or high-energy electrons unsuitable for ECD, and/or controlling a density of low-energy electrons in the plasma.