Accurate Collisional Cross Section Measurement by Multipass Cyclic Ion Mobility Spectrometry

Area of Science:

• Analytical Chemistry
• Biophysical Chemistry
• Separation Science

Background:

• Ion mobility-mass spectrometry (IM-MS) is crucial for structural characterization, providing collision cross section (CCS) values for analyte identification.
• Drift tube ion mobility spectrometry (DT-IMS) offers direct CCS calculation but suffers from limited mobility resolution due to path length constraints.
• Cyclic IMS (cIMS) with traveling wave ion mobility (TWIM) offers higher resolution but faces calibration challenges, especially for multipass analyses.

Purpose of the Study:

• To develop a novel calibration strategy for multipass cIMS analyses to overcome limitations of existing methods.
• To address path length- and mobility-dependent variations in ion drift time, a key challenge in multipass calibration.
• To enable accurate and reproducible CCS measurements using the high mobility resolution of multipass cIMS.

Main Methods:

• Developed a novel calibration strategy specifically for multipass cIMS, targeting the root causes of drift time variations.
• Implemented an algorithm for reconstructing arrival time distributions to handle peak splitting caused by wrap-around in cIMS.
• Applied the new method to characterize four isomeric trisaccharides, comparing results with single-pass and DT-IMS data.

Main Results:

• The novel multipass calibration strategy yielded CCS values with an average deviation of only 0.1% compared to single-pass analyses.
• Measured cIMS CCS values showed excellent agreement with reported DT-IMS CCS values, with an average difference of 0.5%.
• The method successfully resolved subtle mobility characteristics of isomeric trisaccharides, achieving previously unattainable detail and accuracy.

Conclusions:

• The new calibration strategy and reconstruction algorithm significantly improve the accuracy and reproducibility of CCS measurements in multipass cIMS.
• This approach effectively eliminates the need for meticulous separation time selection, simplifying cIMS data acquisition and analysis.
• Researchers can now leverage the high mobility resolution of multipass cIMS without compromising CCS measurement accuracy, broadening its applicability.