Chromatogram Interference Detection via Peak Fit Residuals
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Solution Overview
Problem
Current methods for detecting interferences and artefacts in chromatograms, such as those used in liquid chromatography-mass spectrometry, rely on unreliable parameters like the quantifier/qualifier ratio and require significant manual review, which can lead to incorrect patient results and increased workload, especially when dealing with isomeric compounds or assays lacking a second transition.
Innovation Solution
A computer-implemented method that retrieves chromatograms, applies peak fit modeling, determines residual information, and detects interferences or artefacts by comparing these residuals with a pre-determined threshold, allowing for automated detection without relying on peak shape assumptions or manual review.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Extent of automation
If quantifier/qualifier ratio is used for interference detection, then automated detection can be performed, but detection reliability deteriorates due to low precision and susceptibility to isomeric compound interferences
Solution Approach 1:
The patent changes the detection parameter from quantifier/qualifier ratio to peak shape parameters (asymmetry factor, full width at half maximum, standard deviation). These parameters are less susceptible to interference from isomeric compounds and provide more reliable automated detection without requiring manual review.
Solution Approach 2:
The patent replaces the chemical-based detection approach (relying on mass transition ratios) with a mathematical/statistical approach (analyzing peak shape parameters and residuals). This substitution enables more robust automated detection that is not affected by the presence of isomeric compounds.
2Reliability
If manual peak review is performed to verify chromatograms, then detection reliability improves, but productivity deteriorates due to increased workload and time consumption
Solution Approach 1:
The patent enables the system to automatically detect and flag potential interferences using peak shape analysis and residual evaluation. This self-service capability eliminates the need for manual review while maintaining high detection reliability, thereby improving productivity without sacrificing accuracy.
Solution Approach 2:
The patent implements automated feedback mechanisms where peak shape parameters and residual analyses continuously monitor chromatograms for anomalies. This real-time automated feedback replaces manual verification, maintaining reliability while significantly improving throughput and productivity.
3Device complexity
If peak shape assumptions are made for interference detection, then device complexity is reduced, but measurement precision deteriorates due to inaccuracies when actual peaks deviate from assumed shapes
Solution Approach 1:
The patent uses dynamic peak shape parameters (asymmetry factor, full width at half maximum, standard deviation) that adapt to the actual peak characteristics in each chromatogram. Rather than assuming fixed peak shapes, the method calculates parameters based on the actual data, maintaining precision while avoiding the complexity of sophisticated modeling.
Solution Approach 2:
The patent applies a practical level of peak shape analysis that captures the essential characteristics without over-complicating the model. By focusing on key parameters like asymmetry and width rather than attempting to model every aspect of peak behavior, the method achieves high precision with moderate complexity.
4Measurement precision
If isomeric compounds are present in the sample, then detection reliability improves for compound identification, but interference detection capability deteriorates because isomers produce similar mass transitions
Solution Approach 1:
The patent moves the detection from the mass spectrum dimension to the temporal dimension by analyzing peak shape characteristics over time. Since isomeric compounds may have different chromatographic behaviors (different peak shapes, retention times, or asymmetries), this dimensional shift enables interference detection even when mass transitions are identical.
Solution Approach 2:
The patent applies local quality analysis by examining specific regions of the chromatogram (peak regions) and calculating local parameters such as asymmetry factor and full width at half maximum for each peak. This localized analysis detects subtle differences in peak morphology that indicate interference, even when overall mass spectral patterns are similar.
Data Source
AI summary
A computer-implemented method for detecting at least one interference and/or at least one artefact in at least one chromatogram determined by at least one mass spectrometry device (110) is proposed. The chromatogram comprises a plurality of raw data points. The method comprises the following steps:a) retrieving the at least one chromatogram by at least one processing device (126);b) applying at least one peak fit modelling to the chromatogram by using the processing device (126);c) determining information about residuals of the raw data points by using the processing device (126);d) detecting the at least one interference and/or the at least one artefact by using the processing device (126) by comparing the determined information about the residuals with at least one pre-determined threshold, wherein, if the determined information about the residuals exceed the pre-determined threshold, the at least one interference and/or the at least one artefact is detected.