DDA Mass Spectrometry with Overlapping Isolation Window Deconvolution
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Solution Overview
Problem
Current data-dependent acquisition (DDA) methods in mass spectrometry face challenges in deconvolving precursor ion and product ion relationships within a single time cycle due to co-isolation of multiple precursor ions, leading to difficulties in identifying compounds, especially in complex samples.
Innovation Solution
The implementation of scanning SWATH acquisition during the MS/MS isolation and fragmentation process, using overlapping precursor ion mass selection windows to correlate precursor and product ions, and applying matrix multiplication equations to determine the corresponding precursor ions from product ion spectra in a single time cycle.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a narrow precursor ion mass selection window is used to isolate a single precursor ion, then the specificity of precursor ion selection is improved, but multiple precursor ions representing different compounds can still be co-isolated due to high sensitivity, leading to loss of information about precursor-product relationships
Solution Approach 1:
The precursor ion mass selection window is divided into multiple narrow isolation windows that are scanned sequentially across the mass range. Each narrow window isolates specific precursor ions, and the sequential scanning creates segmented product ion spectra that can be deconvolved to restore precursor-product relationship information.
Solution Approach 2:
The patent introduces a temporal dimension by scanning the mass selection window across different m/z values over time. This creates a fourth dimension (time/scan position) that allows deconvolution of co-isolated precursor ions by analyzing how product ion intensities vary as the isolation window moves through the mass range.
2Loss of information
If product ion spectra are collected over multiple time cycles, then there is sufficient data to deconvolve precursor ion relationships, but the analysis time increases and real-time identification is lost
Solution Approach 1:
The patent performs preliminary scanning of the precursor ion mass range to identify candidate precursor ions before performing the detailed MS/MS analysis. This preliminary action allows the system to focus subsequent scanning and deconvolution efforts on specific mass regions, reducing the total analysis time required.
Solution Approach 2:
The mass selection window is scanned continuously across the precursor ion mass range without interruption, collecting product ion spectra at each step. This continuous scanning approach ensures that all necessary data for deconvolution is collected in a single time cycle, eliminating the need for multiple separate acquisition cycles.
3Productivity
If a single product ion spectrum is used for compound identification, then the analysis is simple and fast, but the identification accuracy decreases when multiple precursor ions are co-isolated
Solution Approach 1:
The patent introduces an intermediary computational deconvolution process that takes the raw product ion spectra from sequential scanning and mathematically separates the contributions of different precursor ions. This intermediary step preserves the speed of single-spectrum analysis while achieving the accuracy of multiple spectra through computational processing.
Data Source
AI summary
Systems and methods are disclosed for performing a DDA mass spectrometry experiment. A precursor ion survey scan of a mass range is performed to generate a precursor ion peak list. A series of steps are performed for each precursor ion peak of the peak list. A peak mass range including the precursor ion peak is selected. A precursor ion mass selection window with a width smaller than the peak mass range is canned across the peak mass range in overlapping steps, producing a series of overlapping windows across the peak mass range. Each overlapping precursor ion mass selection window of the series is fragmented. Product ions produced from each overlapping precursor ion mass selection window of the series are mass analyzed, producing a product ion spectrum for each overlapping precursor ion mass selection window of the series and a plurality of product ion spectra for the peak.