Drift Tube Ion Mobility: How to Reconstruct Collision Cross Section Distributions from Arrival Time Distributions?

Ion mobility spectrometry allows one to determine ion collision cross sections, which are related to ion size and shape. Collision cross sections (CCS) are usually discussed based on the peak center, yet the width of each peak contains further information on the distribution of collision cross sections of each conformational ensemble. Here, we analyze how to convert arrival time distributions (ATD) to CCS distributions (CCSD). With a calibration curve taking into account the CCS dependence of the time spent outside the mobility region, one can reconstruct CCS distributions with correct peak center values. However, the peak widths are incorrectly rendered because ion diffusion, which affects the peak width in the time domain, is irrelevant to collision cross sections. For drift tube ion mobility, we describe a new method, coined "FWHMstep", using a step-field experiment and processing the peak's full width at half-maximum to reconstruct CCSDs. The width of the CCS distribution helps to characterize the analyte's structural heterogeneity, and/or its flexibility (i.e., the variety of ways the analyte ions can rearrange following electrospray into kinetically stable gas-phase conformations).