Ion-Ion Reaction Cell Arrest for High-Charge Protein Signal Preservation

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Solution Overview

Problem

Current methods for analyzing proteins, peptides, and polypeptides by mass spectrometry using ion-ion reactions face challenges in effectively arresting ion-ion reactions, particularly for analyte ions with high charge states, which leads to progressive reaction and loss of signal.

Innovation Solution

The implementation of m/z selective arresting of ion-ion reactions within the ion-ion reaction cell of a mass spectrometer system, achieved by applying periodic RF confinement voltages and auxiliary voltage waveforms to selectively kinetically excite reagent and analyte product ions, thereby arresting further reactions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ion-ion reactions are performed in the ion-ion reaction cell, then protein and peptide analysis is achieved, but high charge state analyte ions undergo progressive reactions leading to signal loss

Engineering Contradiction:
Improvesignal preservationVSAvoidreaction control
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies periodic RF confinement voltages to the ion-ion reaction cell to create oscillatory motion of ions. By controlling the frequency and amplitude of these periodic voltages, the system can periodically bring ions together for reactions while also separating them to prevent excessive reactions, thus maintaining signal integrity for high charge state analyte ions throughout the analysis process

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The patent dynamically adjusts the RF confinement voltages during the ion-ion reaction process. By changing the voltage parameters in real-time, the system optimizes ion collision frequency and reaction efficiency while preventing signal loss from progressive reactions, adapting the reaction conditions to maintain measurement precision

Inventive Principle:
Principle #15Dynamics

2Productivity

If conventional ion-ion reaction methods are used, then protein analysis is performed, but signal loss occurs due to uncontrolled progressive reactions of high charge state ions

Engineering Contradiction:
Improveanalysis efficiencyVSAvoidsignal loss
Core Design Contradiction:
ProductivityVSLoss of energy

Solution Approach 1:

The patent implements feedback control by monitoring the state of analyte ions during ion-ion reactions and adjusting the RF confinement voltages accordingly. This feedback mechanism ensures that high charge state analyte ions undergo sufficient reactions for analysis while preventing excessive reactions that would cause signal loss, thereby maintaining both productivity and signal integrity

Inventive Principle:
Principle #23Feedback

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 enhances the analysis of high charge state analyte ions by preventing further ion-ion reactions, thereby preserving the signal and improving the accuracy of protein, peptide, and polypeptide analysis.

Implementation Method 1

ions have oscillatory motion frequencies that are primarily determined by their mass-to-charge ratios

Methodology Applied
Scientific EffectOscillatory motion: Harmonic Oscillator

Implementation Method 2

a first set of frequency components of one or more of said auxiliary waveform voltages provides m/z selective kinetic excitation to the reagent ions

Methodology Applied
Scientific EffectKinetic excitation: Electromagnetic Induction

Data Source

PatentUS12347665B2Rapid identification and sequence analysis of intact proteins in complex mixtures
Publication Date: 2025.07.01 THERMO FINNIGAN LLC
  • US12347665B2 patent drawing
  • US12347665B2 patent drawing
  • US12347665B2 patent drawing

AI summary

The present disclosure relates to novel and improved methods of analyzing proteins, peptides and polypeptides by mass spectrometry using ion-ion reactions. More specifically the disclosure relates to improved methods for implementing the m/z selective arresting of ion-ion reactions within the ion-ion reaction cell of a mass spectrometer system during a period where ion-ion reactions are performed.