Beam-Splitting Ion Guide for High-Dynamic-Range MS1 Scans
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Solution Overview
Problem
The dynamic range of MS1 spectra in tandem mass spectrometry is limited, leading to issues such as missed precursor targets and hindered identification and quantitation, particularly in Data Dependent Acquisition (DDA) and Data Independent Acquisition (DIA) experiments, due to the limitations of existing methods like Boxcar and HDR scanning, which increase time requirements and ion losses.
Innovation Solution
An ion guide is introduced that splits an ion beam into two portions using a beam splitting electrode, allowing simultaneous filling of SIM injections for a high dynamic range (HDR) MS1 scan alongside a series of MS2 scans, utilizing a DC gradient and RF electrodes to guide ions to separate outlets, enhancing ion transmission and reducing transit time losses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the Boxcar or HDR method is used to improve the dynamic range of MS1 spectra, then the dynamic range is increased, but the time required to accumulate ions significantly increases
Solution Approach 1:
The invention divides the ion beam into multiple separate beams using a beam splitting electrode, allowing parallel accumulation of ions for different m/z ranges. This segmentation enables simultaneous data collection across multiple isolation windows, thereby increasing dynamic range without proportionally increasing total accumulation time.
Solution Approach 2:
The invention introduces a spatial dimension by creating multiple parallel ion beam paths through the beam splitting electrode. Instead of sequentially accumulating ions in a single path, the system utilizes multiple spatial paths to accumulate ions simultaneously, effectively adding a dimensional aspect to the ion accumulation process.
2Measurement precision
If multiple isolation windows are used to increase dynamic range, then detection sensitivity for weak peaks is improved, but the time required to switch voltages and accumulate ions increases
Solution Approach 1:
The invention maintains continuous ion accumulation across multiple parallel beams while different voltage switching occurs for each beam independently. This allows the useful action of ion accumulation to continue without interruption in other beams, eliminating the time loss associated with sequential voltage switching.
Solution Approach 2:
By segmenting the ion beam into multiple independent paths, each path can undergo voltage switching and accumulation independently and simultaneously. This segmentation allows parallel execution of voltage switching operations, reducing the total time required compared to sequential switching.
3Measurement precision
If the C-Trap capacity is increased to accommodate more ions, then the dynamic range is improved, but the space charge effects become more detrimental
Solution Approach 1:
The invention segments the ion population across multiple parallel beams, distributing ions that would otherwise accumulate in a single large trap. This segmentation allows each beam to accumulate fewer ions simultaneously, reducing space charge effects while maintaining overall dynamic range through the combined capacity of multiple beams.
Solution Approach 2:
Instead of increasing capacity in a single accumulation dimension, the invention distributes ions across multiple spatial dimensions (parallel beams). This dimensional approach allows the system to handle larger total ion populations without concentrating them in a single location where space charge effects would be detrimental.
4Loss of information
If sequential MS1 and MS2 scans are performed, then precursor information is obtained, but the time available for MS2 scans is reduced
Solution Approach 1:
The invention merges the MS1 and MS2 accumulation processes by simultaneously accumulating precursor ions in one beam while fragment ions from MS2 scans are analyzed in parallel. This merging of operations allows both precursor information gathering and MS2 scanning to occur concurrently, increasing the overall rate of MS2 scans without sacrificing precursor information quality.
Solution Approach 2:
By establishing parallel ion beam paths, the system enables continuous useful action in both MS1 and MS2 modes simultaneously. While one beam accumulates precursors for MS1 analysis, other beams can be used for MS2 fragment ion accumulation and analysis, maintaining continuous productivity without sequential interruptions.
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 improves the dynamic range of MS1 scans by enabling parallel accumulation of precursor ions, reducing ion losses, and minimizing time overhead, thus enhancing the sensitivity and efficiency of tandem mass spectrometry.
Implementation Method 1
a beam splitting electrode arranged to direct a first portion of the packet of ions towards the first outlet region and a second portion of the packet of ions towards the second outlet region
Implementation Method 2
utilizing a DC gradient and RF electrodes to guide ions to separate outlets
Implementation Method 3
utilizing a DC gradient and RF electrodes to guide ions to separate outlets
Data Source
AI summary
Ion guides comprise an inlet region for receiving a packet of ions; a first outlet region for ejecting ions; a second outlet region for ejecting ions; and a beam splitting electrode arranged to direct a first portion of the packet of ions towards the first outlet region and a second portion of the packet of ions towards the second outlet region.