Multi-Ion Quantitation for Extended LC-MS Dynamic Range
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Solution Overview
Problem
The linear dynamic range (LDR) in liquid chromatography-mass spectrometry (LC-MS) is limited by the ion efficiency of quantifier ions, leading to either short sample concentration range with high ion efficiency or longer range but lower detection sensitivity with lower ion efficiency, requiring significant effort to optimize method and data processing for extended LDR.
Innovation Solution
A system and method for calculating an uncertainty weighted average of the equalized amounts of two or more quantifier ions using a processor, selecting a reference ion and calculating ratios to infer compound quantities, thereby extending the LDR without additional method optimization or data processing effort.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a quantifier ion with high ion efficiency is selected, then detection sensitivity is improved, but the sample concentration range is shortened due to early saturation
Solution Approach 1:
The patent combines multiple quantifier ions with different ion efficiencies into a single consensus quantity calculation. By merging the information from high ion efficiency ions (for sensitivity) and low ion efficiency ions (for extended concentration range), the system achieves both improved detection sensitivity and extended sample concentration range simultaneously, resolving the contradiction between these two parameters.
2Quantity of substance
If a quantifier ion with low ion efficiency is selected, then the sample concentration range is extended, but detection sensitivity is reduced
Solution Approach 1:
The patent merges multiple quantifier ions with different ion efficiencies into a consensus quantity calculation. Low ion efficiency ions extend the concentration range, while high ion efficiency ions provide sensitivity. By combining them through the consensus quantity formula, the system achieves both extended concentration range and maintained detection sensitivity.
3Quantity of substance
If multiple quantifier ions are used to extend LDR, then the concentration range is improved, but method optimization and data processing complexity increases
Solution Approach 1:
The system performs self-service by automatically selecting optimal quantifier ions and calculating their consensus quantity without requiring manual method optimization. The automated ion selection and consensus quantity calculation reduce the complexity of method development and data processing while extending the concentration range through multi-ion analysis.
Solution Approach 2:
The patent changes the parameter of ion selection from manual optimization to automated selection based on ion efficiency characteristics. By dynamically selecting ions and calculating consensus quantities based on their individual efficiencies, the system extends concentration range while reducing method optimization effort through algorithmic parameter adjustment.
Data Source
AI summary
An uncertainty weighted average of the equalized amounts of two or more quantifier ions is calculated from a quantitation experiment itself. n known i ions of a compound are mass analyzed over time in each of m different samples, producing n XIC peaks for each of the m samples. A reference ion j is selected that is a j ion of the n i ions or a hypothetical ion j. A ratio r(j,i) of a peak area of the j ion to a peak area of each ion of the n i ions is calculated for each of the m samples, producing m r(j,i) ratios for each of the n i ions. An expected ratio rq(j,i) is calculated for each ion of the n i ions from the m r(j,i) ratios for each of the n i ions. For each sample, the uncertainty weighted average is calculated using rq(j,i).