Targeted Mass Spectrometry Scheduling for Variable Elution Peaks

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Solution Overview

Problem

Targeted mass spectrometry techniques face limitations in acquisition scheduling and throughput, particularly due to the variability in elution peak widths of analytes, leading to under-sampling and over-sampling issues, which affect quantitative accuracy and instrument resource utilization.

Innovation Solution

Implementing a dynamic acquisition cycle period that varies over time based on the time-varying elution peak widths of target analytes, combined with load balancing to prioritize and schedule analyte analysis, ensuring optimal sampling rates and resource allocation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a fixed acquisition cycle period is used for targeted mass spectrometry, then the instrument scheduling is simple, but under-sampling and over-sampling issues occur due to variability in elution peak widths

Engineering Contradiction:
Improvequantitative accuracyVSAvoidacquisition scheduling complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies dynamics by transitioning from a fixed acquisition cycle period to a dynamic acquisition cycle period that varies over time. The system adjusts the acquisition cycle period based on the elution peak widths of analytes, making the scheduling adaptive to changing conditions during the chromatographic run. This resolves the contradiction by enabling precise sampling (improving quantitative accuracy) while maintaining manageable complexity through automated adjustment based on peak width measurements.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent changes the parameter of acquisition cycle period from a constant value to a time-varying parameter. By monitoring elution peak widths and adjusting the acquisition cycle period accordingly, the system optimizes sampling rates for different analytes. This parameter change allows the system to adapt to varying peak widths without requiring complex manual scheduling, thus improving quantitative accuracy while keeping the system relatively simple.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If mass spectra are acquired continuously for every target analyte, then quantitative accuracy is improved, but instrument resource utilization deteriorates due to over-sampling

Engineering Contradiction:
Improvequantitative accuracyVSAvoidinstrument throughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent applies local quality by implementing different acquisition strategies for different analytes based on their individual elution peak widths. Instead of using a uniform continuous acquisition approach for all analytes, the system adjusts the acquisition cycle period locally for each analyte or time period. This ensures that analytes with narrow peaks receive more frequent sampling (improving quantitative accuracy) while analytes with broad peaks are sampled less frequently (improving instrument throughput), thus resolving the contradiction.

Inventive Principle:
Principle #3Local quality

3Measurement precision

If the acquisition cycle period is shortened to prevent under-sampling, then quantitative accuracy improves, but instrument resource wastage increases due to over-sampling

Engineering Contradiction:
Improvequantitative accuracyVSAvoidinstrument resource wastage
Core Design Contradiction:
Measurement precisionVSLoss of energy

Solution Approach 1:

The system dynamically adjusts the acquisition cycle period based on real-time monitoring of elution peak widths. When narrow peaks are detected, the system shortens the acquisition cycle period to prevent under-sampling and maintain quantitative accuracy. When broad peaks are detected, the system lengthens the acquisition cycle period to avoid over-sampling and reduce instrument resource wastage. This dynamic adaptation resolves the contradiction by optimizing the acquisition cycle period for each specific condition.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent implements feedback by monitoring elution peak widths and using this information to adjust the acquisition cycle period. The system continuously evaluates the peak width of eluting analytes and modifies the sampling rate accordingly. This feedback mechanism ensures that the acquisition cycle period is optimized for each analyte's characteristics, preventing both under-sampling (which would compromise quantitative accuracy) and over-sampling (which would waste instrument resources), thus resolving the contradiction.

Inventive Principle:
Principle #23Feedback

Data Source

PatentEP4471825A1Acquisition scheduling and load balancing for targeted mass spectrometry
Publication Date: 2024.12.04 THERMO FINNIGAN LLC
  • EP4471825A1 patent drawingFigure 1
  • EP4471825A1 patent drawingFigure 2
  • EP4471825A1 patent drawingFigure 3A~3B

AI summary

A computing device for mass spectrometry generates an acquisition schedule that schedules acquisition, by a mass spectrometer, of a set of mass spectra for each target analyte included in a plurality of target analytes included in a sample as the plurality of target analytes elute from a separation system. The acquisition schedule specifies a dynamic acquisition cycle period that varies over time. The computing device further directs the mass spectrometer to acquire the mass spectra in accordance with the acquisition schedule. In some examples, an acquisition schedule is generated by identifying an analyte group corresponding to each analyte included in a list of analytes estimated to be present in the sample and selecting, from the list of analytes, the set of target analytes based on selection criteria and the analyte group corresponding to each respective analyte included in the list of analytes.