Hybrid Ion Pre-Separation for Narrower MS Isolation Windows
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Solution Overview
Problem
Existing mass spectrometry techniques face challenges in achieving high sensitivity and selectivity due to limitations in isolation width and precursor m/z range, leading to decreased duty cycle and complex, unidentifiable spectra.
Innovation Solution
A hybridized ion pre-separation system that spatially separates precursor ions based on both mobility and mass-to-charge ratio (m/z) before MS analysis, using a first pre-separation device for mobility separation and a second device for m/z-based separation, synchronized with a mass spectrometer to optimize precursor ion isolation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If wider isolation widths are used, then a wider precursor m/z range can be analyzed and more precursor ion species can be detected, but the data quality decreases due to co-isolation and co-fragmentation of neighboring analytes
Solution Approach 1:
The patent divides the precursor ion population into multiple subsets based on ion mobility before mass analysis. Each subset is then analyzed separately with a narrower isolation window, preventing co-isolation of neighboring analytes while maintaining coverage of a wide overall m/z range through the combination of multiple segmented analyses.
Solution Approach 2:
The patent introduces ion mobility as an additional separation dimension beyond the traditional mass-to-charge ratio. This fourth dimension (adding mobility to m/z, charge, and retention time) allows ions to be separated and sorted before mass analysis, enabling narrower isolation windows without losing precursor ion coverage.
2Measurement precision
If narrower isolation widths are used, then data quality with greater sensitivity is achieved, but fewer precursor ion species can be analyzed due to narrower precursor m/z range
Solution Approach 1:
The precursor ion population is segmented into multiple subsets based on ion mobility characteristics. Each subset can then be analyzed with a narrow isolation window to achieve high data quality and sensitivity, while the collection of all subsets collectively covers a wide precursor m/z range.
Solution Approach 2:
Ion mobility-based pre-separation is performed before the mass analysis step. This preliminary sorting of ions into mobility-based subsets allows subsequent narrow isolation windows to efficiently capture the relevant precursor ions without missing species, as the ions are already organized by mobility properties.
3Measurement precision
If narrower isolation widths are used, then sensitivity and selectivity are improved, but the duty cycle decreases due to filtering out a large number of precursor ions
Solution Approach 1:
By segmenting ions into mobility-based subsets before analysis, the system can use narrow isolation windows for each subset without excessively reducing the duty cycle. The segmentation pre-organizes the ion population so that narrow windows efficiently capture the relevant ions in each subset, improving both sensitivity and maintaining productivity.
Solution Approach 2:
Ion mobility acts as an intermediary separation mechanism between ionization and mass analysis. This intermediary step pre-sorts ions by mobility, allowing the subsequent narrow mass isolation windows to operate more efficiently with less ion loss, thereby maintaining a higher duty cycle while achieving improved sensitivity.
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
Improves the duty cycle and sensitivity of MS analysis by allowing narrower m/z isolation windows while analyzing a greater number of precursor ions, resulting in higher-quality data with increased selectivity.
Implementation Method 1
a first pre-separation device configured to spatially separate precursor ions into a plurality of subsets of precursor ions according to mobilities of the precursor ions
Implementation Method 2
a second pre-separation device configured to sequentially emit a plurality of packets of precursor ions based on a mass-to-charge ratio (m/z) of the precursor ions
Data Source
AI summary
A system includes a first pre-separation device configured to perform a first pre-separation of precursor ions according to mobilities of the precursor ions and a second pre-separation device positioned downstream of the first pre-separation device configured to perform a second pre-separation of precursor ions based on a mass-to-charge ratio (m/z) of the precursor ions. The system further includes a mass spectrometer positioned downstream of the second pre-separation device configured to acquire mass spectra for precursor ions emitted from the second pre-separation device. The second pre-separation device is synchronized with the mass spectrometer such that an m/z range of precursor ions emitted from the second pre-separation device corresponds to a precursor m/z isolation window of the mass spectrometer.