Mass Spectrometry m/z Segmentation for High-Dynamic Range Scans
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Solution Overview
Problem
Existing mass spectrometry methods, particularly in ion trap-based analyzers like Orbitrap instruments, face limitations in dynamic range and signal-to-noise ratios due to overfilling of the trap, which is exacerbated by the dominance of high-abundance species in samples like human blood plasma, leading to poor detection of lower-abundant species.
Innovation Solution
A method for partitioning the mass-to-charge ratio (m/z) range into dynamically adjustable sub-ranges based on ion abundance, allowing sequential injection and mass analysis of these sub-ranges with individually tailored mass filters and injection times to enhance dynamic range and signal-to-noise ratios, without requiring post-processing calibration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a single injection time is used for all m/z ranges in a full scan, then the injection process is simple and fast, but the dynamic range is limited and low-abundance species cannot be detected with sufficient signal-to-noise ratio
Solution Approach 1:
The patent divides the full m/z scan range into multiple sub-ranges (first m/z sub-range, second m/z sub-range, etc.) and assigns different injection times to each sub-range based on the abundance characteristics of ions in that range. This segmentation allows the system to optimize injection parameters for both high-abundance and low-abundance species simultaneously, thereby expanding the dynamic range without requiring complete redesign of the injection system.
Solution Approach 2:
The patent implements a dynamic injection time distribution mechanism where the injection time is adjusted according to the specific m/z sub-range being analyzed. The system transitions from a static single injection time approach to a dynamic multi-injection-time approach, where each sub-range receives an optimized injection time based on its ion abundance characteristics, resolving the contradiction between simplicity and performance.
2Quantity of substance
If the injection time is determined by automatic gain control based on total ion current, then the control mechanism is simple, but the injection time is dominated by high-abundance species and low-abundance species are not resolved
Solution Approach 1:
The patent segments the total ion population into different abundance groups corresponding to different m/z sub-ranges. By determining injection times separately for each sub-range rather than using a single AGC-based injection time for the entire spectrum, the system can optimize detection for low-abundance species in each segment without being dominated by high-abundance species in other segments.
Solution Approach 2:
The patent applies different injection time parameters to different local regions (m/z sub-ranges) of the spectrum based on their specific ion abundance characteristics. This local optimization allows each sub-range to have injection parameters tailored to its needs, improving signal-to-noise ratio for low-abundance species while maintaining overall system functionality.
3Quantity of substance
If sequential injection of multiple m/z ranges is performed, then the dynamic range is improved, but the acquisition time increases
Solution Approach 1:
The patent implements a partial sequential injection strategy where the full m/z range is divided into sub-ranges that are injected in sequence, but the sequencing is optimized to minimize total acquisition time. By carefully managing the injection sequence and timing for each sub-range, the system achieves enhanced dynamic range while keeping the time penalty acceptable through efficient resource utilization during the sequential process.
Data Source
AI summary
Methods for acquiring mass spectral data of a sample across at least a portion of an m/z range comprise receiving mass spectral data across the m/z range and partitioning the m/z range into one or more sets of m/z sub-ranges, each set comprising one or more m/z sub-ranges, by dividing the m/z range into a plurality of m/z bins, determining an indication of ion abundance for each m/z bin, based on the mass spectral data, and forming an m/z sub-range of the one or more sets of m/z sub-ranges by assigning m/z bins having ion abundances that correspond to at least a threshold degree to the formed m/z sub-range. A mass analysis is performed on the sample for each set of m/z sub-ranges, thereby acquiring one or more partial mass spectral data sets.