2D MS/MS Precursor Window Cycling for Faster Peak Profiling
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Solution Overview
Problem
Existing mass spectrometry methods, particularly in data-independent acquisition modes, face limitations due to the complexity of samples and require additional separation methods like ion mobility, which increase cost and instrument complexity, and are time-consuming when profiling wide mass ranges, especially in high-performance chromatography experiments.
Innovation Solution
A method involving multiple cycles of mass spectrometry operation where a mass separator or filter selectively transmits precursor ions of a single mass or range, varying with time, and operates in both wideband and fragmentation modes to correlate precursor and fragment ions, using calibration procedures to determine accurate mass-to-charge ratios.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a narrow mass filter window is stepped through a wide mass range to improve mass resolution and reduce interference, then measurement precision is improved, but the time required for data acquisition increases significantly
Solution Approach 1:
The mass range is divided into multiple segments or windows that are scanned sequentially. Instead of using a single narrow filter window across the entire mass range, the system segments the analysis into multiple faster scans, each covering a portion of the total mass range. This segmentation allows the system to maintain narrow window precision while reducing the total time required to cover the full range.
Solution Approach 2:
The mass filter window is stepped through predetermined positions in a periodic cyclic manner rather than linearly scanning through the entire range. The window rapidly cycles through multiple mass ranges in sequence, with each cycle covering the full range. This periodic stepping approach enables faster data acquisition by overlapping the time required to profile chromatographic peaks across multiple cycles.
2Measurement precision
If a narrow mass filter window is used to profile chromatographic peaks accurately, then measurement precision is improved, but the time required exceeds the peak elution time in high-performance chromatography
Solution Approach 1:
The system performs rapid periodic cycling of the mass filter window through multiple positions, completing multiple full-range scans within the time it would take a single slow linear scan. This allows the system to capture chromatographic peak information across multiple cycles, maintaining accurate profiling while operating on a timescale compatible with high-performance chromatography peak elution rates.
Solution Approach 2:
Instead of pausing at each mass range position to complete a full profile before moving to the next, the system continuously cycles through all mass range positions in rapid succession. This continuous cycling ensures that data collection is ongoing throughout the chromatographic peak elution, maximizing the use of available ion signals and enabling accurate peak profiling within the constrained time window.
3Measurement precision
If ion mobility separation is added to filter the ion population before fragmentation to improve assignment confidence, then measurement precision is improved, but device complexity and cost increase
Solution Approach 1:
The system segments the ion population analysis by using multiple narrow mass filter windows that are stepped through the mass range. Each window provides a focused view of a specific mass range, effectively segmenting the complex mixture into manageable portions. This segmentation approach achieves interference reduction and assignment confidence similar to ion mobility separation but using only the existing mass filter, avoiding additional instrument complexity.
4Measurement precision
If the mass filter window is stepped through predetermined positions to reduce interference, then measurement precision is improved, but the time required to cover a wide mass range increases
Solution Approach 1:
The mass filter window steps through predetermined positions in a rapid periodic cycle, repeatedly scanning the same mass range segments in sequence. Rather than performing a single slow linear scan across the entire mass range, the system cycles through the same set of predetermined window positions multiple times. This periodic repetition allows the system to maintain high assignment accuracy while reducing the total time required to profile the complete mass range.
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 enables faster and more accurate profiling of chromatographic peaks, reducing the time required for data acquisition and improving the precision of mass-to-charge ratio determination, thus overcoming the limitations of existing methods.
Implementation Method 1
mass selectively transmitting precursor ions of a single mass, or range of masses, through or out of a mass separator or mass filter at any given time, wherein the mass separator or mass filter is operated such that the single mass or range of masses capable of being transmitted therefrom is varied with time
Implementation Method 2
operating the mass separator or filter in a wideband mode between at least some of said plurality of cycles, wherein in each wideband mode the mass separator or filter transmits ions in a non-mass resolving manner; and mass analysing ions
Data Source
Figure 1~3A
Figure 3B
Figure 3C~3D
AI summary
A method of mass spectrometry is disclosed comprising: performing a plurality of cycles of operation during a single experimental run, wherein each cycle comprises: mass selectively transmitting precursor ions of a single mass, or range of masses, through or out of a mass separator or mass filter at any given time, wherein the mass separator or mass filter is operated such that the single mass or range of masses transmitted therefrom is varied with time; and mass analysing ions.