High Resolution Ion Mobility Spectrometry

This dissertation advances high-resolution ion mobility spectrometry (IMS) through two key innovations: (1) precision control of ion motion in Structures for Lossless Ion Manipulation (SLIM), and (2) signal enhancement via field-switching repeller (FSR) techniques to counteract ion depletion effects. First, a stepwise optimization protocol for traveling wave (TW) profiles and inverse gating patterns in SLIM is developed. By coupling analytical ion trajectory simulations with experimental tuning of TW parameters (amplitude, speed, symmetry), this work achieves resolution improvements >30% for structurally similar ions (e.g., peptide isomers), while preserving ion throughput. Second, a field-switching repeller (FSR) method is introduced to mitigate ion depletion in flowing atmospheric-pressure afterglow (FAPA) drift tube IMS. Rapid polarity switching of the repeller field boosts signal intensity by >2× and reduces limits of detection (LOD) by minimizing losses at the ion sampling interface. Theoretical and experimental results confirm that FSR operation extends linear dynamic range without compromising resolving power. Together, these contributions address critical challenges in IMS: SLIM optimizations refine resolution for complex separations, while FSR techniques enhance sensitivity for trace analysis. Applications to biomolecular and environmental samples demonstrate the synergy of these approaches in pushing IMS performance boundaries.