FAIMS-MS Isomer Quantification via Dynamic CV Switching
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Solution Overview
Problem
High Field Asymmetric Ion Mobility Spectrometry (FAIMS) devices face challenges in quantifying mixed isomers due to overlapping compensation voltage (CV) tuning curves, which complicates their use as a filter for unwanted components in mixtures, affecting measurement accuracy and sensitivity.
Innovation Solution
A method and apparatus for FAIMS-MS that involves varying the compensation voltage among multiple values to measure the intensity of ion beams, using a weighting matrix derived from pure isomer CV tuning curves, and applying techniques like matrix inversion or least squares to determine the intensity of each isomer, even when CV tuning curves overlap.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If FAIMS is used as a filter to separate unwanted components in isomer mixtures, then separation efficiency is improved, but measurement precision deteriorates due to overlapping CV tuning curves
Solution Approach 1:
The system dynamically switches between FAIMS separation mode and MS detection mode, and further into non-separating mode for quantification. By making the FAIMS device operational state dynamic rather than static, the system can optimize for separation when needed and for accurate measurement when needed, resolving the contradiction between separation efficiency and measurement precision.
Solution Approach 2:
The measurement process is segmented into distinct operational phases: FAIMS separation phase for removing unwanted components, and non-separating MS phase for accurate quantification. This segmentation allows each phase to optimize its specific function without compromising the other, addressing the contradiction between filtration capability and measurement accuracy.
2Adaptability or versatility
If multiple isomers are separated using FAIMS, then separation capability is improved, but device complexity increases due to overlapping CV tuning curves
Solution Approach 1:
The FAIMS-MS system is designed to perform multiple functions: it can operate in FAIMS separation mode for removing unwanted components from isomer mixtures, switch to MS detection mode for analyzing transmitted ions, and further switch to non-separating mode for accurate quantification of all isomers. This multi-functionality allows a single system to handle complex separation challenges without requiring multiple specialized devices, thereby improving versatility while managing complexity.
3Productivity
If CV is optimized for one isomer, then transmission efficiency is improved, but sensitivity for other isomers deteriorates
Solution Approach 1:
The system employs periodic switching between different operational modes: during FAIMS separation cycles, transmission efficiency is optimized for specific isomers; during non-separating MS cycles, sensitivity for all isomers is maximized. This periodic alternation between optimization targets allows the system to achieve both high transmission efficiency for separation and high sensitivity for quantification across different time periods.
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
Enables accurate quantification of isomers in mixtures by effectively separating and measuring the intensity of each isomer, improving measurement precision and sensitivity, even when CV tuning curves overlap, allowing for real-time determination of intensity contributions.
Implementation Method 1
separation of gas-phase ions is accomplished by exploiting variations in ion drift velocities under an applied electric field arising from differences in ion mobility
Implementation Method 2
ions in the separation gap experience an alternating electric field. The alternating field, which can be a bi-sinusoidal RF waveform, has high field portions and low field portions that are asymmetric but of equal area and opposite sign
Implementation Method 3
measuring the intensity of an ion beam transmitted by the FAIMS device, or product ions derived therefrom, at a mass-to-charge ratio
Data Source
AI summary
A method of analyzing a sample by high-field asymmetric waveform ion mobility-mass spectrometry (FAIMS-MS) is disclosed. An ion beam containing ions of a plurality N of isomers is directed into a FAIMS device. The compensation voltage (CV) at which the FAIMS device is operated is varied among a plurality M of values. For each of the M CV values, an intensity of the ion beam transmitted by the FAIMS device, or product ions derived therefrom, is measured at a mass-to charge ratio corresponding to the plurality N of isomers. The intensities of each of the plurality N of isomers is determined using a set of linear equations, relating the weighted measured intensity values at each value M of the CV and the intensities of each of the N isomers when the FAIMS device is in a non-separation condition.