Ion Trap Reference Ion Release for Mass Spectrometry Calibration

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Solution Overview

Problem

Conventional mass spectrometry calibration methods using lock mass corrections face challenges such as signal suppression from internal reference compounds, mechanical complexity with external references, and loss of analyte data during reference acquisition, leading to inaccurate or impossible calibration.

Innovation Solution

A method involving an ion trap to generate and control the release of reference ions separately from analyte ions, allowing for stable and reliable reference ion supply, avoiding saturation of the detector, and enabling simultaneous analysis of both ions without interrupting the analyte ionization process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If internal reference compounds are used for lock mass correction, then calibration accuracy is improved, but signal suppression occurs and ion statistics become poor

Engineering Contradiction:
Improvecalibration accuracyVSAvoidreference ion signal intensity
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention separates the reference ion source from the analyte ion source, creating two independent ionization pathways. This segmentation allows the reference compound to be ionized separately without competing with the analyte for charge, thereby maintaining strong reference ion signals while avoiding signal suppression and preserving ion statistics for both reference and analyte measurements.

Inventive Principle:
Principle #1Segmentation

2Quantity of substance

If external reference techniques are used, then signal suppression is avoided, but mechanical complexity increases and analyte data is lost during reference acquisition

Engineering Contradiction:
Improvereference ion signal intensityVSAvoidacquisition switching mechanism
Core Design Contradiction:
Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention merges the external reference ion source with the existing analyte ionization system by introducing the reference compound into the same ion source. This combination eliminates the need for separate reference ion sources and complex switching mechanisms, while the reference ion is introduced at such low concentration that it does not significantly compete for charge, avoiding signal suppression.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention enables continuous simultaneous acquisition of both analyte and reference ion signals without interrupting the analyte ionization process. By using a single ion source that generates both ion types concurrently, the system maintains continuous analyte data collection while simultaneously acquiring reference ion signals for calibration, eliminating data loss and the need for acquisition switching.

Inventive Principle:
Principle #20Continuity of useful action

3Measurement precision

If reference compound is mixed into analyte prior to ionisation, then internal reference is achieved, but charge competition suppresses reference ion signal

Engineering Contradiction:
Improvecalibration accuracyVSAvoidion signal suppression
Core Design Contradiction:
Measurement precisionVSObject-generated harmful factors

Solution Approach 1:

The invention applies local quality by introducing the reference compound at a specific location within the ion source where it undergoes preferential ionization. By controlling the introduction point and local concentration, the reference ion is generated with sufficient intensity without significantly competing for charge with the analyte, thereby maintaining both calibration accuracy and reference signal strength.

Inventive Principle:
Principle #3Local quality

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 ensures accurate calibration while maintaining high sensitivity and quantitative fidelity by controlling the release of reference ions, reducing mechanical complexity, and preventing analyte data loss, thus improving the robustness and efficiency of mass spectrometry.

Implementation Method 1

providing an ion trap between the ion source for generating reference ions and the analyser; directing reference ions from the ion source for generating reference ions into the ion trap and trapping the reference ions therein

Methodology Applied
Scientific EffectIon trapping: Electrostatic Induction

Implementation Method 2

releasing reference ions from the ion trap into the analyser, wherein the trapped reference ions are controllably released from the ion trap such that only a portion of the reference ions trapped in the ion trap are released at any given time

Methodology Applied
Scientific EffectIon ejection: Electrostatic Induction

Implementation Method 3

providing an analyser; directing analyte ions from the ion source for generating analyte ions into the analyser without the analyte ions passing into the ion trap, and analysing the analyte ions in the analyser

Methodology Applied
Scientific EffectIon analysis: Electrophoresis

Data Source

PatentUS9728383B2Method of calibrating ion signals
Publication Date: 2017.08.08 MICROMASS UK LTD
  • US9728383B2 patent drawing
  • US9728383B2 patent drawing
  • US9728383B2 patent drawing

AI summary

A method of mass or ion mobility spectrometry is disclosed comprising: providing an ion source for generating analyte ions and reference ions; providing a mass analyzer or ion mobility separator (IMS); providing an ion trap between the ion source and the mass analyzer or IMS; guiding reference ions from the ion source into the ion trap and trapping the reference ions in the ion trap; guiding the analyte ions from the ion source into the mass analyzer or IMS, wherein the analyte ions bypass the ion trap; and releasing reference ions from the ion trap into the mass analyzer or IMS for analysis.