PNNL

Abstract

Ion mobility-mass spectrometry (IMS-MS) is increasingly used to analyze complex samples and provide structural information of unknown compounds. As the complexity of samples increases, there is a need to improve the resolution of IMS-MS instruments to increase the rate of molecular identification. In this work, we evaluated a cyclable and variable-pathlength multilevel Structures for Lossless Ion Manipulations (SLIM) platform to achieve a higher resolving power than previously possible. This new multilevel SLIM platform has eight separation levels connected by ion escalators and a path length of ~88 meters (~11 meters per level). Our new multilevel SLIM can also be operated in an ‘ion cycling’ mode where a set of return ion escalators transport ions from the eighth back to the first level, allowing even longer path lengths (and higher IMS resolution). The platform has been improved to enhance the ion transmission and IMS separation quality by reducing the spacing between SLIM boards as well as board thickness, reducing the ions’ escalator residence time. Compared to the previous generation, the new multilevel SLIM demonstrated a better transmission for a set of phosphazene ions, especially for the low-mobility ions. The new multilevel SLIM achieved better resolving powers than our previous 4-level SLIM. The collision cross-section-based resolving power of the SLIM platform was tested using a pair of singly-charged reverse sequence peptides (SDGRG1+, GRGDS1+). We achieved 1100 resolving power using 88 meters of path length (i.e., 8 levels) and 1400 following an additional pass through the eight levels (i.e., 16 levels or 173.5 m). The multilevel SLIM was further evaluated to demonstrate the enhanced separation for a positively and negatively charged brain total lipid extract sample. The new multilevel SLIM enables much higher resolving powers for a wide range of ion mobilities, improved transmission for low-mobility ions, and the ability to perform even higher resolving power for ions of interest.