Mass Spectrometry Ion Population Control Using Elution Prediction

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Solution Overview

Problem

Conventional automated gain control (AGC) methods in mass spectrometry fail to accurately regulate ion population due to the dynamic and fast-changing nature of ion flux during LC-MS or GC-MS analyses, leading to overshooting or undershooting the target number of ions, which degrades analytical performance, especially in non-Gaussian ion flux profiles.

Innovation Solution

A method involving a machine learning model trained to predict the next detection point in an elution profile based on a series of mass spectra, allowing for precise setting of ion accumulation time to prevent overfilling or underfilling, and enabling data-dependent acquisitions at optimal times.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If ion population is increased to improve signal intensity, then detection sensitivity is improved, but space charge effects increase causing mass spectral distortion and reduced measurement precision

Engineering Contradiction:
Improvemass spectral accuracyVSAvoidspace charge effects
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The system performs preliminary actions by predicting future ion populations based on historical data from previous mass spectra and chromatographic information. This allows the control system to proactively adjust ion population parameters before space charge effects become problematic, preventing mass spectral distortion before it occurs.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system implements feedback control by continuously monitoring actual ion populations, comparing them against predicted values, and adjusting acquisition parameters accordingly. The control system uses the difference between predicted and actual ion populations to modify subsequent acquisition parameters, maintaining optimal ion population levels and preventing space charge effects.

Inventive Principle:
Principle #23Feedback

2Measurement precision

If ion population is regulated to reduce space charge effects, then mass spectral accuracy is improved, but signal intensity may decrease reducing detection sensitivity

Engineering Contradiction:
Improvemass spectral accuracyVSAvoidion population
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The system dynamically adjusts ion population parameters based on real-time conditions and predictions. Rather than maintaining a static ion population, the control system continuously modifies acquisition parameters to achieve optimal ion population levels that balance signal intensity with prevention of space charge effects, adapting to changing chromatographic conditions.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system changes acquisition parameters such as ion source temperature, gas flow rates, and injection timing to control ion population dynamically. By adjusting these parameters based on predicted ion populations, the system maintains optimal ion levels that provide sufficient signal intensity while preventing excessive ion populations that would cause space charge effects.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If more mass spectra are acquired to improve data quality, then measurement precision is improved, but analysis time increases reducing productivity

Engineering Contradiction:
Improvedata qualityVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The system performs preliminary actions by predicting when ion populations will reach optimal or problematic levels based on chromatographic information and historical data. This allows the system to acquire mass spectra at optimally timed intervals rather than continuously or at fixed intervals, reducing the total number of spectra needed while maintaining data quality.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system uses partial action by acquiring mass spectra only when necessary based on predicted ion population levels and chromatographic conditions. Rather than acquiring spectra continuously or at every possible point, the system selectively acquires data at critical points where information is most valuable, reducing analysis time while maintaining measurement precision.

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentEP4478395B1Systems and methods of ion population regulation in mass spectrometry
Publication Date: 2026.04.29 THERMO FINNIGAN LLC
  • EP4478395B1 patent drawingFigure 1
  • EP4478395B1 patent drawingFigure 2A
  • EP4478395B1 patent drawingFigure 2B

AI summary

A method of performing mass spectrometry comprises obtaining, based on a series of mass spectra of detected ions derived from components eluting from a chromatography column, a plurality of extracted ion chromatograms (XICs), each XIC comprising a plurality of detection points representing detected intensity for a distinct selected m/z as a function of time; detecting, based on the series of mass spectra, precursor ions of each distinct selected m/z of the plurality of XICs; and determining, for each XIC based on a set of detection points of the XIC, a predicted next detection point to be obtained based on a next mass spectrum to be acquired.