An Interlaboratory Evaluation of Drift Tube Ion Mobility–Mass Spectrometry Collision Cross Section Measurements

TLDR

Collision cross section measurements from ion mobility–mass spectrometry offer a promising orthogonal dimension of structural information, yet interlaboratory standardization is required before widespread adoption. The study presents a reference drift tube ion mobility mass spectrometer that delivers standardized nitrogen CCS values for over 120 ion species with the lowest measurement uncertainty reported to date. Reproducibility of these DTCCSN2 values was evaluated across three additional laboratories using a commercial DTIM‑MS instrument. Across the three labs, the stepped field method achieved a 0.29 % RSD, while the calibrated single field method had an average 0.54 % bias relative to the reference, underscoring DTIM‑MS’s potential as a reliable molecular identifier.

Abstract

Collision cross section (CCS) measurements resulting from ion mobility–mass spectrometry (IM-MS) experiments provide a promising orthogonal dimension of structural information in MS-based analytical separations. As with any molecular identifier, interlaboratory standardization must precede broad range integration into analytical workflows. In this study, we present a reference drift tube ion mobility mass spectrometer (DTIM-MS) where improvements on the measurement accuracy of experimental parameters influencing IM separations provide standardized drift tube, nitrogen CCS values (DTCCSN2) for over 120 unique ion species with the lowest measurement uncertainty to date. The reproducibility of these DTCCSN2 values are evaluated across three additional laboratories on a commercially available DTIM-MS instrument. The traditional stepped field CCS method performs with a relative standard deviation (RSD) of 0.29% for all ion species across the three additional laboratories. The calibrated single field CCS method, which is compatible with a wide range of chromatographic inlet systems, performs with an average, absolute bias of 0.54% to the standardized stepped field DTCCSN2 values on the reference system. The low RSD and biases observed in this interlaboratory study illustrate the potential of DTIM-MS for providing a molecular identifier for a broad range of discovery based analyses.