Mass Spectrometer Watch Mode Quantitation

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Solution Overview

Problem

Current mass spectrometry techniques face challenges in selectively detecting and quantifying specific target molecules in complex mixtures due to false positive triggers from near isobaric co-isolated interferences and the need for separate calibration curve experiments.

Innovation Solution

A system and method that utilize a watch mode to acquire mass spectra from multiple internal standard variants, generating a calibration curve and then transitioning to a quantitation mode to determine the target analyte concentration based on the calibration curve and quantitation mode mass spectrum, reducing false positives and eliminating the need for separate calibration experiments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If internal standard triggered-parallel reaction monitoring is used for target molecule quantitation, then quantitation capability is improved, but false positive triggering occurs due to near isobaric co-isolated interferences

Engineering Contradiction:
Improvetarget molecule quantitation accuracyVSAvoidfalse positive triggering
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent segments the internal standard verification process into multiple distinct mass transitions (precursor ion to fragment ion pairs) rather than relying on a single transition. By monitoring multiple segmented transitions simultaneously, the system can distinguish true internal standards from near isobaric interferences, as genuine internal standards will produce all expected fragment ions with characteristic intensity ratios, while interferences will fail to produce the complete pattern.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a verification mechanism that acts as an intermediary between detecting internal standard ions and triggering quantitation mode. This intermediary step checks whether multiple fragment ion transitions are present and whether their intensity ratios match expected values before allowing the quantitation trigger to activate, thereby filtering out false positives from near isobaric interferences.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If separate calibration curve experiments are conducted for absolute quantitation, then quantitation accuracy is improved, but analysis time and complexity increase

Engineering Contradiction:
Improveabsolute quantitation accuracyVSAvoidanalysis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent merges the calibration curve generation process with the target analyte quantitation analysis into a single integrated experiment. By spiking the sample with internal standards at multiple known concentrations and simultaneously acquiring data for both calibration and quantitation, the method eliminates the need for separate calibration experiments, reducing total analysis time while maintaining absolute quantitation accuracy through the use of multiple internal standard variants.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent makes the internal standard variants serve multiple functions: they act as both calibration standards (providing known concentration references for building the calibration curve) and as triggers for quantitation mode (initiating targeted acquisition of the target analyte). This multi-functionality allows a single experimental run to accomplish both calibration and quantitation tasks that traditionally required separate experiments.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 enhances the specificity and efficiency of target analyte detection and quantitation by using multiple internal standard variants to conditionally trigger quantitation, reducing false positives and allowing for absolute quantitation in a single sample analysis.

Implementation Method 1

a mass analyzer for separating the ions based on their mass-to-charge ratio

Methodology Applied
Scientific EffectMass-to-charge ratio separation:

Implementation Method 2

an ion detector for detecting the separated ions

Methodology Applied
Scientific EffectIon detection:

Data Source

PatentUS11232936B2Absolute quantitation of a target analyte using a mass spectrometer
Publication Date: 2022.01.25 THERMO FINNIGAN LLC
  • US11232936B2 patent drawing
  • US11232936B2 patent drawing
  • US11232936B2 patent drawing

AI summary

A targeted quantitation system for mass spectrometry may acquire, while operating in a watch mode, a watch mode mass spectrum including mass peaks for ions produced from a plurality of internal standard variants added to a sample comprising a target analyte. Each internal standard variant included in the plurality of internal standard variants includes a unique isotopologue of the target analyte and is added to the sample in a unique amount. The targeted quantitation system may generate a calibration curve based on the watch mode mass spectrum. The targeted quantitation system may acquire, while operating in a quantitation mode, a quantitation mode mass spectrum including mass peaks for ions produced from the target analyte included in the sample. The targeted quantitation system may determine a concentration of the target analyte included in the sample based on the calibration curve and the second mass spectrum.