Rounded Turn\nSLIM Design for High-Resolution Ion Mobility\nMass Spectrometry Analysis of Small Molecules

Various rounded turn designs in Structures for Lossless\nIon Manipulation\n(SLIM) were explored via ion trajectory simulations. The optimized\ndesign was integrated into a SLIM ion mobility (IM) system coupled\nwith a time-of-flight (TOF) mass spectrometer (MS) for further experimental\ninvestigation. The SLIM-TOF IM-MS system was assessed for IM resolution\nand ion transmission efficiency across a wide <i>m</i>/<i>z</i> range using various RF frequencies and buffer gas combinations.\nHigh ion transmission efficiency and high resolution ion mobility\n(HRIM) separation were achieved for Agilent tune mix ions through\na ∼12.8 m serpentine separation path in both nitrogen and helium.\nIn helium, ion transmission for low <i>m</i>/<i>z</i> ions was enhanced at higher RF trapping frequency, enabling the\ndetection of ions with <i>m</i>/<i>z</i> below\n50 and all 17 amino acids from a standard mixture. Lossless ion transmission\nwas observed for glycine (<i>m</i>/<i>z</i> 76)\nin both passthrough and HRIM modes. HRIM resolution was benchmarked\nusing <i>L</i>-isoleucine, <i>L</i>-leucine, and\nvarious other isobaric and isomeric metabolites with <i>m</i>/<i>z</i> values of 60–89. This work demonstrates\na rounded turn SLIM design that enables HRIM measurements for small\nmolecule analytes, with a particular focus on metabolomics, where\nIM offers a means to enhance the speed, robustness, and specificity\nof analytical workflows.