Quantitative Mass Analysis Using Concurrent Ion Isolation

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Solution Overview

Problem

Conventional ion trap mass spectrometry methods introduce inaccuracies and high relative standard deviation in quantitative mass analysis due to fluctuations in the ionization process, requiring separate ion injection events for analytes and internal standards.

Innovation Solution

A method and system for concurrent isolation and fragmentation of analyte and internal standard precursor ions within a single ion injection event in an ion trap mass analyzer, using collision-induced dissociation and notched waveforms to generate unique product ions for precise quantification, allowing for simultaneous analysis and determination of analyte amounts through a calibration curve.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If separate ion injection events are used for analytes and internal standards, then quantitative mass analysis can be performed, but measurement accuracy deteriorates due to ionization process fluctuations

Engineering Contradiction:
Improvequantitative mass analysis accuracyVSAvoidmeasurement uncertainty
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent combines the injection of analyte precursor ions and internal standard precursor ions into a single common ion injection event, rather than using separate injection events. This merging approach ensures that both ion types experience identical ionization conditions, eliminating errors from ionization fluctuations and improving measurement accuracy and reliability.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent segments the ion trap mass analyzer operation into distinct phases: (1) concurrent m/z isolation of analyte and internal standard precursor ions using notched waveforms, (2) sequential or simultaneous fragmentation of isolated precursors, and (3) mass analysis of product ions. This segmentation allows precise control over each step while maintaining the benefit of common ion injection.

Inventive Principle:
Principle #1Segmentation

2Productivity

If multiple precursor ions are analyzed in a single ion injection event, then productivity improves, but device complexity increases due to concurrent isolation requirements

Engineering Contradiction:
Improvesample utilization efficiencyVSAvoidisolation control complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent uses notched waveforms as an intermediary control mechanism to selectively isolate specific m/z ranges within the ion trap during a single injection event. These notched waveforms act as frequency-selective filters that allow concurrent isolation of multiple precursor ion types without requiring complex hardware modifications, thus improving productivity while managing device complexity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Device complexity

If conventional separate injection events are used, then device complexity is reduced, but measurement accuracy deteriorates due to ionization fluctuations

Engineering Contradiction:
Improveion injection system simplicityVSAvoidquantitative analysis accuracy
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent changes the control parameters of the ion trap mass analyzer by applying notched waveforms at specific frequencies during the ion injection and isolation phases. This parameter change enables selective m/z isolation of multiple precursor ions simultaneously without requiring hardware modifications, maintaining device simplicity while achieving high measurement accuracy through common ion injection.

Inventive Principle:
Principle #35Parameter changes

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 minimizes errors and uncertainty in quantitative mass analysis, achieving low relative standard deviation and efficient sample utilization by analyzing multiple precursor ions in a single event, thereby improving measurement accuracy and reducing hardware complexity.

Implementation Method 1

The analyte and precursor ions may be fragmented using collision-induced dissociation (CID).

Methodology Applied
Scientific EffectCollision-induced dissociation:

Data Source

PatentUS9911587B1Methods and systems for quantitative mass analysis
Publication Date: 2018.03.06 THERMO FINNIGAN LLC
  • US9911587B1 patent drawing
  • US9911587B1 patent drawing
  • US9911587B1 patent drawing

AI summary

A method of quantitative mass analysis of precursor species of different mass-to-charge (m/z) ratios from the same ion injection event is disclosed. A plurality of precursor ion species is introduced into a mass spectrometer at the same time, and isolated. A first subset of the isolated precursor ions having a first m/z ratio and a second subset of the isolated precursor ions having a second m/z ratio are fragmented. The fragmented ions are analyzed at the same time. A mass spectrum is generated for the fragment ions of the first and second subsets of precursor ions.