Chaminda M. Gamage

Cryogenic Ion Mobility-Mass Spectrometry Captures Hydrated Ions Produced During Electrospray Ionization

Evaporation of water from extensively hydrated protons and peptides formed by electrospray ionization (ESI) has been examined for the first time by cryogenic ion mobility-mass spectrometry (IM-MS). The extent of hydration was controlled using a heated capillary inlet operated between 340 and 391 K. Cold cluster ions formed in the source region were transported into a low temperature (∼80 K) IM drift tube using an electrostatic ion guide where they were separated on the basis of size-to-charge via low-energy collisions with helium gas. The eluting IM profile was subsequently pulsed into an orthogonal time-of-flight (TOF) mass spectrometer for mass-to-charge (m/z) identification of the cluster ion species. Key parameters that influence the cluster distributions were critically examined including the inlet temperature, drift tube temperature, and IM field strength. In agreement with previous studies, our findings indicate that water evaporation is largely dependent upon the particular charge-carrying species within the cluster. IM-MS results for protonated water clusters suggest that the special stability of H(+)(H(2)O)(n) (n = 21) is attributed to the presence of a compact isomer (assigned to a clathrate cage) that falls below the trendline produced by adjacent clusters in the n = 15 to 35 size range. Peptide studies are also presented in which specific and nonspecific solvation is observed for gramicidin S [GS + 2H](2+)(H(2)O)(n) (n = 0 to ∼26) and bradykinin [BK + 2H](2+)(H(2)O)(n) (n = 0 to ∼73), respectively.

Contrast-enhanced differential mobility-desorption electrospray ionization-mass spectrometry imaging of biological tissues.

Mass spectrometry imaging (MSI) performed under ambient conditions is a convenient and information-rich method that allows for the comprehensive mapping of chemical species throughout biological tissues with typical spatial resolution in the 40-200 μm range. Ambient MSI methods such as desorption electrospray ionization (DESI) eliminate necessary sample preparation but suffer from lower spatial resolution than laser-based and vacuum techniques. In order to take advantage of the benefits of ambient imaging and to compensate for the somewhat limited spatial resolution, a secondary orthogonal separation nested in the imaging scheme was implemented for more selective discernment of tissue features in the spectral domain. Differential mobility spectrometry (DMS), an ion mobility-based separation that selectively transmits ions based on their high-to-low electric field mobility differences, can significantly reduce background chemical interferences, allowing for increased peak capacity. In this work, DESI DM-MSI experiments on biological tissue samples such as sea algae and mouse brain tissue sections were conducted using fixed DMS compensation voltages that selectively transferred one or a class of targeted compounds. By reducing chemical noise, the signal-to-noise ratio was improved 10-fold and the image contrast was doubled, effectively increasing image quality.

Damping factor links periodic focusing and uniform field ion mobility for accurate determination of collision cross sections.

The methodology for obtaining accurate ion-neutral collision cross section (Ω) values for peptides and proteins using periodic focusing ion mobility spectrometry (PF IMS) is presented. A mobility dampening factor (represented by the term α) is introduced to account for the relative increase in ion-neutral collisions in PF IMS compared to uniform field ion mobility spectrometry (UF IMS) for equivalent operating conditions. The results show that α may be easily quantified both theoretically and empirically for a specific PF IMS design operating at a given pressure based upon the charge state of the analyte. By simply incorporating an α term into traditional UF IMS expressions, accurate Ω values were obtained with excellent agreement (≤4% difference) compared to UF IMS measurements found in the current literature.

Kinetics of Surface-Induced Dissociation of N(CH3)4+ and N(CD3)4+ Using Silicon Nanoparticle Assisted Laser Desorption/Ionization and Laser Desorption/Ionization

The implementation of surface-induced dissociation (SID) to study the fast dissociation kinetics (sub-microsecond dissociation) of peptides in a MALDI TOF instrument has been reported previously. Silicon nanoparticle assisted laser desorption/ionization (SPALDI) now allows the study of small molecule dissociation kinetics for ions formed with low initial source internal energy and without MALDI matrix interference. The dissociation kinetics of N(CH3)4+ and N(CD3)4+ were chosen for investigation because the dissociation mechanisms of N(CH3)4+ have been studied extensively, providing well-characterized systems to investigate by collision with a surface. With changes in laboratory collision energy, changes in fragmentation timescale and dominant fragment ions were observed, verifying that these ions dissociate via unimolecular decay. At lower collision energies, methyl radical (CH3) loss with a sub-microsecond dissociation rate is dominant, but consecutive H loss after CH3 loss becomes dominant at higher collision energies. These observations are consistent with the known dissociation pathways. The dissociation rate of CH3 loss from N(CH3)4+ formed by SPALDI and dissociated by an SID lab collision energy of 15 eV corresponds to log k = 8.1, a value achieved by laser desorption ionization (LDI) and SID at 5 eV. The results obtained with SPALDI SID and LDI SID confirm that (1) the dissociation follows unimolecular decay as predicted by RRKM calculations; (2) the SPALDI process deposits less initial energy than LDI, which has advantages for kinetics studies; and (3) fluorinated self-assembled monolayers convert about 18% of laboratory collision energy into internal energy. SID TOF experiments combined with SPALDI and peak shape analysis enable the measurement of dissociation rates for fast dissociation of small molecules.

Comparative performance of tripole and quadrupole ion guides at elevated pressure.

This study presents the first practical demonstration of an operational tripole ion guide. The transmission was measured for both the tripole and quadrupole ion guides at 1 Torr pressure. It was found that the quadrupole provides 2.5-3 times better ion transmission efficiency. Two different electric schemes for driving the tripole were tested. Similar transmission characteristics were obtained in both cases. A brief analysis of the tripole performance and ways to improve it is presented.