Differential Mobility Pre-Separation for Higher MS Quantitation Throughput
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Solution Overview
Problem
Mass spectrometry devices face inefficiencies in quantitation throughput due to limited ion capacity and space charge limitations, particularly in handling high ion loads from complex samples, and existing ion accumulation methods do not effectively manage multiple analytes with unpredictable retention times.
Innovation Solution
A system and method utilizing a chromatography column, ion source, mobility separator, and mass analyzer with a controller to optimize ion separation and accumulation based on ion mobility, adjusting parameters like gas flow and electric field to enhance separation and quantitation throughput.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If a quadrupole mass spectrometer transmits ions of a single m/z ratio at a time, then mass resolution is improved, but quantitation throughput deteriorates due to reduced duty cycle
Solution Approach 1:
The invention segments the ion population into multiple groups based on their mobility characteristics using a mobility separator. This segmentation allows the quadrupole to process multiple ion groups in parallel or rapid succession, thereby improving throughput while maintaining mass resolution for each segment.
Solution Approach 2:
The mobility separator performs preliminary separation of ions based on mobility before they enter the quadrupole mass filter. This pre-separation organizes the ion population into distinct groups that can be efficiently processed, reducing the time the quadrupole needs to spend switching between different m/z ratios and improving overall quantitation throughput.
2Adaptability or versatility
If multiple analytes are targeted simultaneously by switching between ions, then the number of analytes analyzed increases, but duty cycle is limited to 1/N
Solution Approach 1:
The ion population is segmented into N groups based on mobility characteristics, where N is the number of ion channels or accumulation regions. This segmentation allows all N groups to be processed simultaneously or in parallel, converting the sequential 1/N duty cycle limitation into an N-fold throughput improvement.
Solution Approach 2:
Multiple ion groups with different m/z ratios but similar mobility characteristics are merged into the same accumulation region or ion channel. This merging allows the system to process multiple analytes simultaneously through parallel accumulation and detection, significantly improving duty cycle while maintaining the ability to resolve individual analytes.
3Measurement precision
If ion accumulation time is increased to improve sensitivity, then detection sensitivity is improved, but ion channel capacity is exceeded causing saturation
Solution Approach 1:
The ion accumulation capacity is segmented into multiple independent ion channels or accumulation regions. Each channel can accumulate ions independently, distributing the total ion load across N channels. This allows each channel to operate within its capacity limits while the system as a process handles a much larger total ion population, preventing saturation.
Solution Approach 2:
The system adds a mobility-based dimension to ion separation, creating multiple accumulation regions along the mobility axis. This dimensional expansion allows simultaneous accumulation of multiple ion populations with different mobility characteristics in parallel, increasing total accumulation capacity without requiring longer accumulation times that would cause saturation in a single channel.
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 quantitation efficiency by optimizing ion separation and accumulation, allowing for simultaneous analysis of multiple analytes with reduced loss and saturation, enhancing the duty cycle and handling capacity beyond traditional limits.
Implementation Method 1
a mobility separator configured to separate ions received from the source based on the mobility in a gas
Implementation Method 2
a chromatography column to perform a chromatographic separation of the sample
Implementation Method 3
a source configured to generate ions from constituent components of the sample received from the chromatography column
Data Source
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AI summary
A system for analyzing a sample includes a source configured to generate ions from constituent components of the sample; a mobility separator configured to separate ions received from the source based on the mobility in a gas; a plurality of ion channels arranged adjacent to the plurality of exit apertures of the mobility separator such that ions from the mobility separator are directed to different channels according to their respective mobility; a mass analyzer configured to determine the mass-to-charge ratio of the ions; and a controller. The controller is configured to identify retention time windows with minimum overlap of ions with similar mobility and sets of ions within the retention time windows; adjust mobility separation parameters for specific sets of ions to optimize separation of compounds; and quantify a plurality of target analytes.