Staggered MRM Mass Spectrometry for Mass Axis Drift Rejection
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Solution Overview
Problem
Mass spectrometry systems face instability due to mass axis drifts, leading to decreased sensitivity and selectivity in LC-MS methods, which current strategies to mitigate this issue often compromise selectivity.
Innovation Solution
Implement staggered-multiple reaction monitoring (S-MRM) using a mass spectrometry device with three channel groups measuring at theoretical and shifted m/z values, comparing quantifier/qualifier ratios to a reference, and rejecting transitions outside a predefined tolerance range to maintain sensitivity and selectivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If multiple precursor ions are monitored simultaneously using a single quadrupole mass filter, then the information obtained about the reaction system increases, but the ability to achieve sufficient precursor isolation and selectivity deteriorates
Solution Approach 1:
The single quadrupole mass filter is divided into multiple independent quadrupole rods (first set and second set), each capable of being independently controlled to transmit different precursor ions simultaneously. This segmentation allows multiple precursor ions to be monitored in parallel while maintaining sufficient isolation and selectivity through independent control of each rod set.
2Productivity
If a single quadrupole mass filter is used, then the device complexity is reduced, but the productivity in terms of multiple reaction monitoring capability is limited
Solution Approach 1:
The quadrupole mass filter is segmented into multiple rod sets that can be independently controlled. This allows the system to monitor multiple reactions simultaneously (increasing productivity) while maintaining a relatively simple overall device structure based on the conventional quadrupole configuration.
Solution Approach 2:
The modified quadrupole mass filter with multiple rod sets serves multiple functions: it can transmit multiple different precursor ions simultaneously, perform parallel multiple reaction monitoring, and maintain the ability to perform traditional single-ion monitoring. This multi-functionality increases productivity without proportionally increasing device complexity.
3Loss of time
If multiple precursor ions are transmitted through the same quadrupole, then the analysis time is reduced, but the resolution between different ion paths deteriorates
Solution Approach 1:
By dividing the quadrupole into multiple independently controllable rod sets, the system can transmit multiple precursor ions through different spatial paths within the same quadrupole structure. This allows simultaneous analysis of multiple reactions (reducing analysis time) while maintaining resolution between different ion paths through independent control of each rod set's transmission parameters.
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
S-MRM maintains sensitivity and selectivity of LC-MS methods by stabilizing mass axis drifts, enhancing ion transmission and detection accuracy.
Implementation Method 1
a first set of quadrupole rods and a second set of quadrupole rods in a single quadrupole mass filter are each independently controlled to transmit different selected precursor ions
Data Source
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AI summary
A method for multiple reaction monitoring using a mass spectrometry device (106) is proposed. The method comprises the following steps: i) (128) measuring, by using the mass spectrometry device (106), multiple reaction monitoring transitions of quantifier and qualifier of both an internal standard and an analyte using staggered- multiple reaction monitoring, wherein the staggered-multiple reaction monitoring comprises at least three multiple reaction monitoring channel groups, wherein one of the multiple reaction monitoring channel groups measure at respective theoretical m/z values of the quantifier and qualifier of both the internal standard and the analyte and the two other multiple reaction monitoring channel groups measure at respective m/z values shifted to higher and lower values by a predefined level; ii) (130) comparing, for at least two groups, at least two of the quantifier/qualifier ratios of the multiple reaction monitoring transitions of the internal standard with a reference value from a database (126) by using at least one processing device (120), wherein the comparison comprises determining a deviation between the quantifier/qualifier ratios and the reference value; iii) (132) determining from the analyte and the internal standard measured multiple reaction monitoring transitions a measurement result by using the processing device (120), if the deviation for at least one of the quantifier/qualifier ratios is within at least one predefined tolerance range, otherwise rejecting (136) the measured multiple reaction monitoring transitions.