Browsing by Subject "Ion Mobility-Mass Spectrometry"
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Item High Resolution Ion Mobility Spectrometry with Increased Ion Transmission: Exploring the Analytical Utility of Periodic-Focusing DC Ion Guide Drift Cells(2012-02-14) Blase, Ryan ChristopherDrift tube ion mobility spectrometry (IMS) is a powerful, post-ionization separation that yields structural information of ions through an ion-neutral collision cross section. The ion-neutral collision cross section is governed by the collision frequency of the ion with the neutral drift gas. Consequently, ions of different size will have different collision frequencies with the gas and be separated in the drift cell. A significant challenge for IMS, however, is to separate ions with very similar collision cross sections, requiring higher resolution ion mobility spectrometers. Resolution in IMS is of utmost importance for the separation of complex mixtures, e.g. crude oil samples, proteolytic digests, positional isomers, and ion conformers. However, most methods employed to increase mobility resolution significantly decrease ion transmission through the mobility device. Herein, a periodic-focusing DC ion guide drift cell (PDC IG) is presented to display its potential capabilities for higher mobility resolution with increased ion transmission. The PDC IG utilizes unique electrode geometry compared to the conventional uniform field electrode design. Electrode geometry can be defined by the electrode inner diameter (d), thickness (t), and spacing (s). Specifically, the ratio of d : t : s is equal to, or very near, 1:1:1. The PDC IG electrode design creates a non-uniform (fringing) electric field-especially near the electrode walls. The design also causes variations in the radial electric field which provides an effective RF as ions move through the device and a radially confining effective potential that improves ion transmission through the device. In this dissertation the analytical utility of the PDC IG drift cell for ion mobility separations will be explored. The radial focusing properties of the device will be presented along with studies of electrode geometry and its effect on ion mobility resolution and ion transmission through the drift cell. PDC IG drift cell length is also examined to determine its effect on mobility resolution and ion transmission. Finally, the PDC IG drift cell device is coupled to an orthogonal-acceleration time-of-flight mass spectrometer as well as a modular, PDC IG drift cell being adapted to a commercial qTOF mass spectrometer for IM-MS experiments.Item Investigation on Gas-phase Structures of Biomolecules Using Ion Mobility-mass Spectrometry(2011-08-08) Tao, LeiIM-MS is a 2-D technique which provides separations based on ion shape (ion-neutral collision cross-section, ?) and mass (m/z ratio). Ion structures can be deduced from the measured collision cross-section (?meas) by calculating the collision cross-sections (?calc) of candidates generated by molecular dynamics (MD) and compared with the experiment results. A database of ?s for singly-charged peptide ions is presented. Standard proteins are digested using different enzymes (trypsin, chymotrypsin and pepsin), resulting in peptides that differ in amino acid composition. The majority (63%) of the peptide ion correlates well with the globular structures, but some exhibit ?s that are significantly larger or smaller than the average correlation. Of the peptide ions having larger ?s, approximately 71% are derived from trypsin digestion and most of the peptide ions that have smaller ?s are derived from pepsin digestion (90%). We use computational simulations and clustering methods to assign backbone conformations for singly-protonated ions of the model peptide (NH2-Met-Ile-Phe-Ala-Gly-Ile-Lys-COOH) formed by both MALDI and ESI and compare the structures of MIFAGIK derivatives to test the ?sensitivity? of the cluster analysis method. Cluster analysis suggests that [MIFAGIK + H]+ ions formed by MALDI have a predominantly turn structure even though the low energy ions prefer partial helical conformers. Although the ions formed by ESI have ?s that are different from those formed by MALDI, the results of cluster analysis indicate that the ions backbone structures are similar. Chemical modifications (N-acetyl, methylester, as well as addition of Boc or Fmoc groups) of MIFAGIK alter the distribution of various conformers, the most dramatic changes are observed for the [M + Na]+ ion, which show a strong preference for random coil conformers owing to the strong solvation by the backbone amide groups. ?meas of oligodeoxynucleotides in different length have been measured in both positive and negative modes. For a given molecular weight and charge state, ?meas of the oligodeoxynucleotide ions are smaller than those of the peptides, indicating their different packing efficiency. A novel generalized non-Boltzman sampling MD has been utilized to investigate the gas-phase ion conformations of dGGATC based on the free energy values. Theory predicts only one low-energy conformer for the zwitterionic form of dGGATC- while dGGATC+ ions have several stable conformers in both canonical and zwitterionic form in the gas phase, in good agreement with the experiment.Item The Development and Utilization of the Periodic Focusing Ion Funnel(2014-12-09) Fort, Kyle LoganIon mobility-mass spectrometry (IM-MS) provides gas phase, size-based separation, on an ultrafast timescale (?s-ms). With the incorporation of electrospray ionization, IM-MS is a valuable tool to investigate conformations of biological molecule ions that can be representative of their solution-phase structure. In some cases, evaporative cooling during ESI can kinetically trap these solution-phase structures in local minima along the potential energy surface. However, if the internal energy of the ion is increased via collisional activation, these solution-phase structures can be readily converted to an energetically preferred, gas-phase structure. Radio frequency (RF) confining devices, such as the RF ion funnel, are typically used to increase ion transmission in IM-MS measurements; however, these devices can lead to collisional activation and structural rearrangement due to high voltage oscillation amplitudes (Vp-p). Recently, periodic focusing ion mobility spectrometry (PF IMS) has been shown to provide comparable radial confinement, while utilizing reduced radial electric fields Vp-p as compared to the RF ion funnel. Work presented herein describes the development and characterization of a periodic focusing ion funnel (PF IF) that is capable of increasing ion transmission while being able to preserve nascent conformer distributions and subsequently inducing structural rearrangement. The utility of the PF IF is demonstrated with the neuropeptide Substance P (SP), as it provides a model for studying the structural effects of collisional activation due to the presence of both a kinetically trapped and gas-phase conformer, denoted ASP and BSP, respectively. By increasing the internal energy of [SP + 3H]^3+ ions, ASP is quantitatively converted to BSP, which is consistent with ASP being a kinetically trapped conformer and BSP being a gas-phase conformer. The collision cross section and mobility resolution of the ASP suggests that it is comprised of a broad distribution of compact globular conformations. Intramolecular solvation appears to stabilize the compacted structure of ASP in the gas-phase; however, as the ion?s internal energy increases, these noncovalent interactions are disrupted and the peptide converts into the gas-phase conformation. Mutations of various amino acid residues of SP provide a means of identifying these interactions and their effect on the stability of the kinetically trapped conformers.