Tandem Mass Spectrometer Ion Packet Segmentation for Parallel Analysis
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Solution Overview
Problem
Current tandem mass spectrometry techniques face limitations in throughput and dynamic range, particularly when analyzing multiple low-intensity analytes, due to narrow mass window isolation and limited resolving power, leading to inefficient quantitation and detection challenges.
Innovation Solution
The method employs parallel reaction monitoring (PRM) and a tandem mass spectrometer design that allows for the selection and fragmentation of multiple ion species in parallel, using a single high-resolution spectrum to increase detection limits and dynamic range, while optimizing ion transmission and fragmentation processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a narrow mass range is isolated in the first quadrupole stage, then the specificity and robustness of target analysis is improved, but the throughput and analysis time for multiple targets deteriorates due to low duty cycles
Solution Approach 1:
The invention segments the ion beam into multiple packets based on their m/z ratios using a scanning device. Each packet contains ions of a specific mass range, allowing parallel processing of multiple targets without sacrificing isolation specificity. This segmentation enables the system to analyze multiple compounds simultaneously while maintaining the narrow mass window requirement for each target.
Solution Approach 2:
The invention introduces a temporal dimension by storing ions in a 3D ion trap and ejecting them as time-separated packets. This transforms the traditional single-time-point analysis into a multi-time-point process, where different mass ranges are analyzed in sequential time windows, effectively increasing throughput while maintaining specificity for each target.
2Measurement precision
If high resolution and high mass accuracy spectrum acquisition is used, then the identification capability of ions is improved, but the detection limits and dynamic range for specific m/z deteriorates compared to triple quadrupole
Solution Approach 1:
The invention segments the broad mass range into multiple narrow m/z windows using the ion gate and scanning device. Each segment is analyzed with high resolution and mass accuracy, but the segmentation allows the system to focus its detection capability on specific m/z ranges, thereby achieving both high resolution and good detection limits for targeted compounds.
Solution Approach 2:
The invention uses dynamic control of the ion gate and scanning device to adaptively adjust which mass ranges are transmitted to the high resolution analyzer at different times. This dynamic allocation of analysis resources allows the system to optimize both resolution and detection sensitivity by concentrating ion flux on targeted m/z ranges during specific time windows.
3Productivity
If the ion beam is split into packets for parallel fragmentation, then the analysis throughput is improved, but the time allocated for each scan is reduced
Solution Approach 1:
The invention performs preliminary mass separation and packet formation in the 3D ion trap before fragmentation. By pre-organizing ions into discrete packets with specific m/z ranges, the system enables rapid sequential analysis without requiring lengthy scan times for each packet, as the mass selection is already accomplished before the fragmentation stage.
Solution Approach 2:
The invention implements a nested structure where multiple levels of mass analysis are combined: the 3D ion trap provides broad mass range coverage, the ion gate performs intermediate mass selection, and the high resolution analyzer provides final precise mass measurement. This nested arrangement allows efficient use of scan time at each level, maximizing throughput while maintaining analytical depth.
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 significantly enhances the detection limits and analysis time for multiple low-intensity analytes, overcoming the limitations of traditional triple quadrupole mass spectrometers by enabling the simultaneous analysis of multiple ion species with improved resolving power and dynamic range.
Implementation Method 1
trapping the precursor ions in an ion trap
Implementation Method 2
a first ion gate arranged in a path of precursor ions ejected from the ion trap towards a downstream ion guide
Implementation Method 3
analyzing the resulting ion population derived from the mixed selected subset of ion packets in a high resolution mass analyzer
Data Source
AI summary
A tandem mass spectrometer and method are described. Precursor ions are generated in an ion source and an ion injector injects ions towards a downstream ion guide via a single or multi reflection TOF device that separates ions into packets in accordance with their m/z. A single pass ion page in the path of the precursor ions between the ion injector and the ion guide is controlled so that only a subset of precursor ion packets, containing precursor ions of interest, is allowed onward transmission to the ion guide. A high resolution mass spectrometer is provided for analysis of those ions, or their fragments, which have been allowed passage through the ion gate. The technique permits multiple m/z ranges to be selected from a wise mass range of precursors, with optional fragmentation of one or more of the chosen ion species.