Extending LC-MS Dynamic Range via Multi-Precursor XIC Combination
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Solution Overview
Problem
Current LC-MS and LC-MS/MS methods face limitations in the quantitation dynamic range due to signal plateaus caused by saturation, adducts, dimers, and multiply charged ions, which restrict the maximum concentration that can be measured.
Innovation Solution
The method combines product ion extracted ion chromatograms from multiple precursor ions using a data-independent acquisition (DIA) approach, extending the dynamic range by summing intensities from different precursor ion mass selection windows in LC-MS/MS systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional LC-MS/MS methods use a single precursor ion for quantitation, then the measurement is simple and specific, but the dynamic range is limited due to signal plateaus from saturation and ion formation variations
Solution Approach 1:
The patent combines extracted ion chromatograms (XICs) from multiple precursor ions of the same compound into a single quantitation channel. By merging signals from different precursor ions (e.g., protonated molecules, adducts, dimers), the method extends the linear dynamic range and overcomes signal plateaus that limit traditional single-precursor approaches.
Solution Approach 2:
The patent segments the total ion signal into multiple precursor ion-specific channels, each monitored independently. This segmentation allows the system to capture signal contributions from different ion species across varying concentrations, then recombine them to achieve extended dynamic range quantitation.
2Measurement precision
If multiple precursor ions are monitored simultaneously, then the dynamic range is extended, but the data processing complexity and computational requirements increase
Solution Approach 1:
The patent performs preliminary processing by generating separate XICs for each precursor ion during the acquisition phase. This preliminary segmentation of signals allows for efficient later combination and simplifies the computational task of extending dynamic range, as the heavy lifting of signal separation is done during data acquisition rather than post-processing.
3Measurement precision
If signal intensity is increased to measure higher concentrations, then the detection sensitivity is improved, but signal saturation occurs limiting further measurement
Solution Approach 1:
The patent changes the parameter being measured from a single precursor ion signal to a composite signal from multiple precursor ions. This parameter change allows the system to maintain linear response at higher concentrations by capturing signal contributions from different ion species that have different saturation characteristics, thereby extending the linear dynamic range while maintaining detection sensitivity.
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 effectively increases the quantitation dynamic range by rescuing signal contributions from multiple ion species, allowing for linear response over a broader concentration range, thereby overcoming the limitations of traditional methods.
Implementation Method 1
an ion source device ionizes the sample to transform the sample into an ion beam
Implementation Method 2
the selected precursor ions can be fragmented (e.g., via collision induced dissociation), and the fragmented ions (product ions) can be analyzed
Implementation Method 3
a fluid sample under analysis is passed through a column filled with a chemically treated solid adsorbent material... the different components can have different transit (elution) times through the packed column, resulting in separation of the various components
Data Source
AI summary
Systems and methods are disclosed for determining if the dynamic range of quantitation in mass spectrometry can be extended. A DIA method is performed on a sample for a compound of interest at each acquisition time of a plurality of acquisition times. A plurality of product ion spectra are produced for each window of two or more precursor ion mass selection windows. A known product ion of the compound of interest is selected. Two or more XICs are calculated from two or more different precursor ion windows for the known product ion. A ratio of one XIC of the two or more XICs to at least one other XIC of the two or more XICs is calculated. If the ratio is above a threshold, the XIC is used in the quantitation. If not, two or more XICs can be combined into a single XIC that is used for the quantitation.