New Ion Mobility Measurements Enabled by Innovations in Instrumentation and Modeling

Abstract

This thesis describes the characterization of a novel traveling-wave (TW) ion mobility (IM) device and a method to assess the impacts of experimental conditions on ion internal temperatures. IM is a gas-phase analytical technique that separates analyte ions on the basis of shape, size, and charge and is often coupled with mass spectrometry (MS) to yield structural information on top of mass-to-charge (m/z). Chapter 1 contains an overview of IM-MS techniques, with a particular focus on recent advances and their application to structural studies of biomolecular ions. The following chapters describe experimental and computational approaches to assess activation within TWIM separations, including a novel method for precisely controlled ion heating.Our lab has previously designed and implemented several ion mobility devices constructed using the Structures for Lossless Ion Manipulations (SLIM) architecture, in which ion motion is controlled by potentials applied to mirrored pairs of printed circuit boards; these previous implementations all employed electrostatic fields. Engineering challenges posed by this method led us to consider alternative strategies, including traveling waves. Chapter 2 presents a novel TW-SLIM instrument consisting of two antiparallel IM regions controlled by traveling waves enabling tandem and IM separations involving multiple passes around the SLIM device. Tandem IM separations of native-like protein ions performed with this instrument demonstrate the ability to control protein ion structural states via tuning of applied potentials. Chapter 3 details a statistical method for quantifying the internal temperatures of ions under IM conditions, including those described in Chapter 2. Results of ion trajectory simulations performed on a geometric model of a similar TW-SLIM device indicate that minimal ion heating occurs during transmission through the separation region, while significant ion heating occurs while ions are trapped or stored. Additionally, computational results indicate that instrument parameters including background gas pressure, wave height, and guard electrode potential impact ion temperatures to varying extents. Results from the work described in this dissertation have implications for structural conclusions drawn from ongoing and future IM work, especially as commercialization expands the use of the technique.