LC-MS Analyte Carryover Detection via Chromatogram Background Height

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Solution Overview

Problem

Current methods for evaluating analyte carryover in liquid chromatography mass spectrometry (LC-MS) devices are not suitable for providing information on actual sample measurements, especially in random access mode, where the analyte of the previous sample is different from the analyte of interest.

Innovation Solution

A method that involves determining at least one chromatogram of the sample of interest, calculating the background height of the chromatogram, and using this background height to determine the carryover of the analyte from the previous sample into the sample of interest.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional carryover evaluation methods using blank samples are used, then carryover can be assessed during method development, but this approach is not suitable for providing information on actual sample measurements in random access mode

Engineering Contradiction:
Improvecarryover detection accuracyVSAvoidapplicability to random access mode
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

Instead of using blank samples to detect carryover (traditional approach), the patent uses the actual sample of interest itself by analyzing its chromatogram background. This inversion allows carryover detection to work in random access mode where blank samples are not available, while still maintaining detection accuracy through background height analysis of the sample's own chromatogram

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The sample of interest serves itself for carryover detection by providing its own chromatogram background for analysis. The background height of the sample's chromatogram is used to determine carryover, eliminating the need for separate blank samples and making the method self-sufficient and adaptable to random access workflows

Inventive Principle:
Principle #25Self-service

2Reliability

If re-analysis of samples is triggered after high concentrated samples, then carryover can be corrected, but this is not feasible in random access mode where the analyte of the previous sample is different

Engineering Contradiction:
Improvemeasurement reliabilityVSAvoidoperational feasibility in random access mode
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent performs preliminary detection of carryover by analyzing the background height of the chromatogram before final quantification. This allows carryover to be identified and accounted for in advance, enabling reliable measurements without requiring re-analysis, thus making the method operationally feasible in random access mode where re-runs are not practical

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If background height is used to determine carryover, then actual sample measurements can be evaluated, but this requires new methodology not covered by traditional guidelines

Engineering Contradiction:
Improveapplicability to actual sample measurementsVSAvoidmethod complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent extracts the background height information from the chromatogram of the sample of interest, separating this carryover indicator from the main analyte signal. By focusing specifically on the background portion of the chromatogram, the method simplifies the analysis while enabling carryover detection in actual samples, adding minimal complexity compared to traditional methods

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP4127707B1Monitoring of a carry over of an analyte
Publication Date: 2025.05.21 F HOFFMANN LA ROCHE & CO AG
  • EP4127707B1 patent drawingFigure 1
  • EP4127707B1 patent drawingFigure 2
  • EP4127707B1 patent drawingFigure 3

AI summary

The present invention relates to a method for determining a carry over of an analyte from a previous sample into a sample of interest on a liquid chromatography mass spectrometer (LC-MS) device, the method comprising the following steps: (a) determining at least one chromatogram of said sample of interest on said LC-MS device (2.4); (b)determining a background height of the chromatogram (3.5); and (c) determining the carry over of the analyte from said previous sample into the sample of interest based on the background height. The present invention also relates to methods, systems, and computer program products related to the aforesaid method.