With its capacity to store and translate ions across considerable distances and times, traveling wave structures for lossless ion manipulations (TW-SLIM) provide the foundation to expand the scope of ...ion mobility spectrometry (IMS) experiments. While promising, the dynamic electric fields and consequential ion-neutral collisions used to realize extensive degrees of separation have a considerable impact on the empirical results and the fundamental interpretation of observed arrival time distributions. Using a custom-designed set of TW-SLIM boards (∼9 m) coupled with a time-of-flight mass spectrometer (SLIM-ToF), we detail the capacity to systematically alter the gas-phase distribution of select peptide conformers. In addition to discussing the role charge-transfer may play in TW-SLIM experiments that occur at extended time scales, the ability of the SLIM-ToF to perform tandem IMS was leveraged to confirm that both the compact and elongated conformers of bradykinin2+ undergo interconversion within the SLIM. Storage experiments in which ions are confined within SLIM using static potential wells suggest that factors aside from TW-induced ion motion contribute to interconversion. Further investigation into this matter suggests that the use of radio frequency (RF) fields to confine ions within SLIM may play a role in ion heating. Aside from interconversion, storage experiments also provide insight into charge transfer behavior over the course of extended periods. The results of the presented experiments suggest that considerations should be taken when analyzing labile species and inform strategies for the TW-SLIM design and method development.
•The performance of multiple dynamic traveling wave profiles was evaluated.•Optimal resolution was obtained using a static TW, but the ramp performed similarly.•Regarding SNR, optimum waveform ...profiles were species dependent.•Increases in ion abundance were observed when using a ramped TW for select species.•Tailored waveforms to optimize TW-SLIM separations require continued refinement.
The amenability of traveling wave ion mobility spectrometry (TWIMS) to extended separation pathlengths has prompted a recent surge of interest concerning the technique. While promising, the optimization of ion transmission, particularly when analyzing increasingly disparate species, remains an obstacle in TWIMS. To address this issue, we evaluated a suite of dynamic TW profiles using an original TW structures for lossless ion manipulations (TW-SLIM) platform developed at Washington State University. Inspired by the range of gradient elution profiles used in traditional chromatography, three distinct square TW profiles were evaluated: a static approach which represents a traditional waveform, a dual approach which consists of two distinct TW profiles within a given separation event; and a ramp approach which varies TW speed and amplitude at a fixed rate during separation. The three waveform profiles were evaluated in terms of their impact on separation (quantified as resolution) and sensitivity (quantified using signal-to-noise ratio (SNR), and ion abundance). Concerning separation, the highest resolution (R) was observed when operating with the static waveform (R = 7.92); however, the ramp waveform performed comparably (R = 7.70) under similar conditions. Regarding SNR, optimum waveform profiles were species dependent. Bradykinin2+ displayed the largest gains in SNR (36.6% increase) when ramping TW speed, while the gains were greatest (33.5% increase) for tetraoctylammonium when modulating TW amplitude with the static waveform. Lastly, significant (>10%) increases in the abundance of tetraoctylammonium ions were observed exclusively when utilizing a ramped waveform. The present set of experiments outline the results and challenges related to optimizing separations using alternative TW profiles and provides insight concerning TW-SLIM method development which may be tailored to enhance select analytical metrics.
Traveling wave ion mobility experiments using planar electrode structures (e.g., structures for lossless ion manipulation, TW-SLIM) leverage the mature manufacturing capabilities of printed circuit ...boards (PCBs). With routine levels of mechanical precision below 150 μm, the conceptual flexibility afforded by PCBs for use as planar ion guides is expansive. To date, the design and construction of TW-SLIM platforms require considerable legacy expertise, especially with respect to simulation and circuit layout strategies. To lower the barrier of TW-SLIM implementation, we introduce Python-based interactive tools that assist in graphical layout of the core electrode footprints for planar ion guides with minimal user inputs. These scripts also export the exact component locations and assignments for direct integration into KiCad and SIMION for PCB finalization and ion flight simulations. The design concepts embodied in the set of scripts comprising SLIM Pickins (PCB CAD generation) and pigsim (SIMION workspace generation) build upon the lessons learned in the independent development of the research-grade TW-SLIM platforms in operation at WSU. Due to the inherent flexibility of the PCB manufacturing process and the time devoted to board layouts prior to manufacturing, both scripts serve to enable rapid, iterative design considerations. Because only a few predefined parameters are necessary (i.e., the TW-SLIM monomer width, x position following a TW Turn, and y position following a TW Turn) it is possible to design the exact component layouts and accompanying simulation space in a manner of minutes. There is no known limitation to the board layout capacities of the scripts, and the size of a designed layout is ultimately constrained by the abilities of the final PCB design and simulation tools, KiCad and SIMION, to accommodate the thousands of electrodes comprising the final design (i.e., RAM and software overhead). Toward removing the barriers to exploring new SLIM tracks and the likelihood of layout errors that require considerable revision and engineering time, the SLIM Pickins and pigsim tools (included as Supporting Information) allow the user to quickly design a length of planar ion guide, simulate its abilities to confine and transmit ions, compare hypothetical board outlines to given vacuum chamber dimensions, and generate a near-production ready PCB CAD file. In addition to these tools, this report outlines a series of cost-saving strategies with respect to vacuum feedthroughs and vacuum chamber design for TW ion mobility experiments using planar ion guides.
When operated as a standalone analytical device, traditional drift tube ion mobility spectrometry (IMS) experiments require high-speed, high-gain transimpedance amplifiers to record ion separations ...with sufficient resolution. Recent developments in the fabrication of charge-sensitive cameras (e.g., IonCCD) have provided key insights for ion beam profiling in mass spectrometry and even served as detectors for miniature magnetic sector instruments. Unfortunately, these platforms have comparatively slow integration times (multiple ms), which largely precludes their use for recording ion mobility spectra, where sampling rates into the 10s of kHz are generally required. As a result, experiments that simultaneously probe the longitudinal and transverse mobility of an injected species using an array detector have not been reported. To address this duty-cycle mismatch, a frequency encoding strategy is used to evaluate ion swarm characteristics, while directly capturing ion mobility information using the Fourier transform. This apparatus described allows the ion beam to be profiled over the full course of the experiment and establishes the foundation to examine axial and longitudinal drift velocities simultaneously.
•An overview of ion mobility spectrometry theory and use in glycomics is presented.•Ion polarity, ion adducts, and chromatography can aid glycan mobility separation.•Ion mobility along with ...spectroscopy and tandem mass analysis give structural details.•Computational modeling of glycan ions grants insight into composition and behavior.
Characterization of complex oligosaccharides has historically required extensive sample handling and separations before analysis using nuclear magnetic resonance spectroscopy and electron impact mass spectra following hydrolysis, derivatization, and gas chromatographic separation. Advances in liquid chromatography separations and tandem mass spectrometry have expanded the range of intact glycan analysis, but carbohydrate structure and conformation—integral chemical characteristics—are often difficult to assess with minimal amounts of sample in a rapid fashion. Because ion mobility spectrometry (IMS) separates analytes based upon an effective ‘size-to-charge’ ratio, IMS is, by extension, highly applicable to glycomics. Furthermore, the speed of IMS, its growing levels of separation efficiency, and direct compatibility with all forms of mass spectrometry, illustrates is core role in the future of glycomics efforts. This review assesses the current state of ion mobility–mass spectrometry applied to glycan, glycoprotein, and glycoconjugate analysis. Currently, assessing optimal ion polarity and adduct type for a glycan class along with the appropriate tandem mass spectrometry technique underpin many of the current glycan analysis efforts using ion mobility–mass spectrometry (IMMS). Once determined, these parameters have enabled a growing and impressive range of glycomics campaigns employing this technique. Additionally, the combination of IMS with tandem mass spectrometry, and even spectroscopic methods, further expands the dimensionality of hybrid instrumentation to provide a more comprehensive assessment of glycan structure across a wide dynamic range. Continued computational efforts to complement experimental and instrumental advancements also serve as a core component of IMMS workflows applied to glycomics and promise to maximize the information gained from mobility separations.
Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches ...have been notoriously difficult to establish and differences in the drug used and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized Δ
-tetrahydrocannabinol-rich (CAN
) or cannabidiol-rich (CAN
) whole-plant cannabis extracts. Male Sprague-Dawley rats were trained to nose-poke for discrete puffs of CAN
, CAN
, or vehicle (VEH) in daily 1 h sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CAN
maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared with CAN
or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CAN
administration decreased hippocampal CB1 receptor binding. Removal of CAN
reinforcement (but not CAN
) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.
The evolving legal landscape concerning recreational cannabis use has increased urgency to better understand its effects on the brain and behavior. Animal models are advantageous in this respect; however, current approaches typically used forced injections of synthetic cannabinoids or isolated cannabis constituents that may not capture the complex effects of volitional cannabis consumption. We have developed a novel model of cannabis self-administration using response-contingent delivery of vaporized cannabis extracts containing high concentrations of Δ
tetrahydrocannabinol (THC) or cannabidiol. Our data indicate that THC-rich cannabis vapor has reinforcing properties that support stable rates of responding and conditioned drug-seeking behavior. This approach will be valuable for interrogating effects of cannabis and delineating neural mechanisms that give rise to aberrant cannabis-seeking behavior.
A new instrument configuration for native ion mobility-mass spectrometry (IM-MS) is described. Macromolecule ions are generated by using a static ESI source coupled to an RF ion funnel, and these ...ions are then mobility and mass analyzed using a periodic focusing drift tube IM analyzer and an Orbitrap mass spectrometer. The instrument design retains the capabilities for first-principles determination of rotationally averaged ion-neutral collision cross sections and high-resolution measurements in both mobility and mass analysis modes for intact protein complexes. Operation in the IM mode utilizes FT-IMS modes (originally described by Knorr ( Knorr, F. J. Anal. Chem. 1985, 57(2), 402−406 )), which provides a means to overcome the inherent duty cycle mismatch for drift tube (DT)-IM and Orbitrap mass analysis. The performance of the native ESI-FT-DT-IM-Orbitrap MS instrument was evaluated using the protein complexes Gln K (MW 44 kDa) and streptavidin (MW 53 kDa) bound to small molecules (ADP and biotin, respectively) and transthyretin (MW 56 kDa) bound to thyroxine and zinc.
The rates and mechanisms of chemical reactions that occur at a phase boundary often differ considerably from chemical behavior in bulk solution, but remain difficult to quantify. Ion-neutral ...interactions are one such class of chemical reactions whose behavior during the nascent stages of solvation differs from bulk solution while occupying critical roles in aerosol formation, atmospheric chemistry, and gas-phase ion separations. Through a gas-phase ion separation technique utilizing a counter-current flow of deuterated vapor, we quantify the degree of hydrogen-deuterium exchange (HDX) and ion-neutral clustering on a series of model chemical systems (
i.e.
amino acids). By simultaneously quantifying the degree of vapor association and HDX, the effects of cluster formation on reaction kinetics are realized. These results imply that cluster formation cannot be ignored when modeling complex nucleation processes and biopolymer structural dynamics.
Simultaneous gas-phase hydrogen/deuterium exchange and ion-neutral clustering are monitored in an atmospheric pressure drift cell to quantify the effects of vapor association on observed rates of deuterium incorporation for select amino acids.
Toward the goal of minimizing construction costs while maintaining high performance, a new, reduced-pressure, drift tube ion mobility system is coupled with an ion trap mass analyzer through a custom ...ion shuttle. The availability of reduced-pressure ion mobility systems remains limited due to comparatively expensive commercial options and limited shared design features in the open literature. This report details the complete design and benchmarking characteristics of a reduced-pressure ion mobility system. The system is constructed from FR4 PCB electrodes and encased in a PTFE vacuum enclosure with custom torque-tightened couplers to utilize standard KF40 bulkheads. The PTFE enclosure directly minimizes the overall system expenses, and the implementation of threaded brass inserts allows for facile attachments to the vacuum enclosure without damaging the thermoplastic housing. Front and rear ion funnels maximize ion transmission and help mitigate the effects of radial ion diffusion. A custom planar ion shuttle transports ions from the exit of the rear ion funnel into the ion optics of an ion trap mass analyzer. The planar ion shuttle can couple the IM system to any contemporary Thermo Scientific ion trap mass analyzer. Signal stability and ion intensity remain unchanging following the implementation of the planar ion shuttle when compared to the original stacked ring ion guide. The constructed IM system showed resolving powers up to 85 for various small molecules and proteins using the Fourier transform from a ∼1 m drift tube. Recorded mobilities derived from first principles agree with published literature results with an average error of 1.1% and an average error toward literature values using single field calibration of <1.3%.
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