Ion Mobility and Charge Reduction for CCS Measurement
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Solution Overview
Problem
Existing methods struggle to reliably determine the collision cross-section of high molecular weight ions, particularly for complex biomolecules like virus capsids, due to overlapping charge state peaks in mass spectra.
Innovation Solution
A method involving ion mobility separation in the native state followed by charge reduction and mass spectrometry in a charge-reduced state, allowing for the determination of average mass and charge values, and subsequently calculating the collision cross-section using the Mason-Schamp equation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional mass spectrometry is used to analyze high molecular weight ions, then the analysis can be performed directly, but the charge state peaks overlap making it difficult to determine mass and charge values
Solution Approach 1:
The patent segments the analysis process into two distinct stages: first performing ion mobility separation to resolve ions by their collision cross-section, then performing mass spectrometry on the separated ion packets. This segmentation allows each technique to operate in its optimal regime, with ion mobility providing separation based on size/shape and mass spectrometry providing accurate mass measurement of the separated packets.
Solution Approach 2:
The patent introduces ion mobility separation as an intermediary step between sample introduction and mass spectrometry analysis. This intermediary technique separates the complex mixture of multiply charged ions into distinct packets based on their collision cross-section, thereby resolving the overlapping charge state peaks that would otherwise prevent accurate mass and charge determination.
2Measurement precision
If ion mobility separation is performed alone, then separation based on size and shape is achieved, but additional structural information and compound identification confidence are limited
Solution Approach 1:
The patent merges ion mobility separation with mass spectrometry into a hyphenated technique (IM-MS). By combining these two analytical methods, the system simultaneously obtains collision cross-section information from ion mobility (providing size and shape data) and accurate mass-to-charge ratio information from mass spectrometry (providing molecular weight and compositional data), thereby achieving comprehensive molecular characterization.
Solution Approach 2:
The combined ion mobility-mass spectrometry system performs multiple functions simultaneously: it separates ions by collision cross-section, measures accurate mass-to-charge ratios, determines collision cross-sections for structural information, and provides compound identification through library matching of both CCS and mass data, making it a universally applicable platform for comprehensive molecular analysis.
3Measurement precision
If charge reduction is applied before mass spectrometry, then mass to charge ratio spacings increase improving measurement accuracy, but the ion charge state changes from the native state
Solution Approach 1:
The patent performs preliminary ion mobility separation on the native, multiply charged ions to separate them into distinct packets based on their collision cross-section. This preliminary action occurs before any charge reduction, allowing the separation to be performed on ions in their native state. Subsequently, charge reduction can be applied to each separated packet to improve mass measurement accuracy without affecting the collision cross-section determined during the preliminary separation.
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 enables the accurate determination of collision cross-sections for high molecular weight ions in their native charge state, improving the analysis of complex biomolecules like virus capsids.
Implementation Method 1
packets of ions move at terminal velocity (drift) through the buffer gas with a drift velocity (v) that is related to the strength of the electric field (E) via mobility (K)
Implementation Method 2
packets of analyte ions travel through a gas-filled drift tube under the influence of a uniform electric field
Implementation Method 3
the ion species in the first state is subject to charge reduction to reduce the average charge of the ions to increase the mass to charge ratio spacings between different charge states
Implementation Method 4
measuring mass to charge ratios for the ion species using a mass spectrometer, wherein prior to measuring the mass to charge ratios, the ion species in the first state is subject to charge reduction
Implementation Method 5
using the Mason-Schamp equation: CCS = (3e/16N) * sqrt(2πMm)/(kBT) * (1/K²) where z is the number of charges on the ion
Data Source
AI summary
Disclosed are methods of mass spectrometry that use charge reduction techniques to reduce the average charge of the ions to increase the mass to charge ratio spacings between different charge states for the ion species prior to mass analysis. In embodiments there is disclosed a method for determining a collision cross section for an ion species, wherein an ion mobility is determined for an ion species in a first state without charge reduction and the mass to charge ratios for the ion species are then measured in a second, charge-reduced state. The average charge determined for the ion species in the first state is then used together with the average mass determined from the ion species in the second state and the ion mobility determined for the ion species in the first state to determine a collision cross section for the ion species in the first state.