Combining experimental data with computational modeling, we illustrate the capacity of selective gas-phase interactions using neutral gas vapors to yield an additional dimension of gas-phase ion mobility separation. Not only are the mobility shifts as a function of neutral gas vapor concentration reproducible, but also the selective alteration of mobility separation factors is closely linked to existing chemical functional groups. Such information may prove advantageous in elucidating chemical class and resolving interferences. Using a set of chemical warfare agent simulants with nominally the same reduced mobility values as a test case, we illustrate the ability of the drift-gas doping approach to achieve separation of these analytes. In nitrogen, protonated forms of dimethyl methyl phosphonate (DMMP) and methyl phosphonic acid (MPA) exhibit the reduced mobility values of 1.99 ± 0.01 cm Vs at 175 °C. However, when the counter current drift gas of the system is doped with 2-propanol at 20 μL/h, full baseline resolution of the two species is possible. By varying the concentration of the neutral modifier, the separation factor of the respective clusters can be adjusted. For the two species examined and at a 2-propanol flow rate of 160 μL/h, MPA demonstrated the greatest shift in mobility (1.58 cmVs) compared the DMMP monomer (1.63 cmVs). Meanwhile, the DMMP dimer experienced no change in mobility (1.45 cmVs). The enhancement of separation factors appears to be brought about by the differential clustering of neutral modifiers onto different ions and can be explained by a model which considers the transient binding of a single 2-propanol molecule during mobility measurements. Furthermore, the application of the binding models not only provides a thermodynamic foundation for the results obtained but also creates a predictive tool toward a quantitative approach.

Through vapor modification of the counter-current drift gas in an atmospheric pressure drift tube ion mobility spectrometer (IMS), we demonstrate measurement of gas-phase association enthalpies and entropies for select proton-bound heterodimers formed from a phosphonic acid with 2-propanol. Previous efforts to determine gas-phase association thermodynamic properties have relied largely upon lower pressure systems and inference of the relative concentrations of m/z isolated species. In contrast, the drift tube IMS based approach developed and applied in this study leverages the explicit gas-phase equilibrium that is established within an ion mobility drift cell. The inferred enthalpies and entropies of association are based solely upon monitoring a shift in the arrival time of an ion at different temperatures (and not on the signal intensity or on external instrument drift time calibration). We specifically report the gas-phase Gibbs free energy, enthalpy, and entropy changes for the association of 2-propanol with protonated methyl, ethyl, and propyl phosphonic acid ions (MPA, EPA, PPA) across the 100− 175 °C temperature range. For all of these proton-bound heterodimers, the standard enthalpies and entropies of 2-propanol association were negative and positive, respectively. These data indicate that proton-bound heterodimer formation is both enthalpically and entropically favorable, though we find that the magnitude of the standard enthalpy change for vapor association is small (near 1 kcal/mol for all examined heterodimers). Though many prior results (largely obtained with high pressure mass-spectrometry) for other proton-bound organic heterodimer complexes show larger enthalpic favorability and an entropic barrier, our results qualitatively conform to the bulk Kelvin−Thomson−Raoult (KTR) model, which is commonly utilized in describing ion-induced nucleation of a vapor onto a soluble, nanometer scale ion. The KTR model suggests that heterodimer formation due to vapor binding to an ion should be slightly enthalpically favored (due to a larger Thomson effect than the Kelvin effect) and entropically favored because of ion solvation (Raoult's effect). The method presented in this study can be applied to any static-field ion mobility spectrometer and to a wide variety of heterodimers. Due to the ease of implementation and broad applicability, this approach may find consistent use in determining the thermodynamic properties of weakly bound gas-phase heterodimer complexes which are difficult to probe via alternative techniques. Moreover, this renewed implementation of the IMS experiment is directly compatible with soft ionization sources which will enable the characterization of vapor modifier-induced mobility shift experiments for larger molecular complexes.

For time dispersive ion mobility experiments detail control over the mechanism of ion beam modulation is necessary to establish optimum performance as this parameter greatly influences the temporal width of the ion beam arriving at the detector.

Ion mobility spectrometry employing structures for lossless ion manipulations (SLIM-IMS) is an attractive gas-phase separation technique due to its ability to achieve unprecedented effective ion path lengths (>1 km) and IMS resolving powers in a small footprint. The emergence of multilevel SLIM technology, where ions are transferred between vertically stacked SLIM electrode surfaces, has subsequently allowed for ultralong single-pass path lengths (>40 m) to be achieved, enabling ultrahigh resolution IMS measurements to be performed over the entire mobility range in a single experiment. Here, we report on the development of a 1 m path length miniature SLIM module (miniSLIM) based on multilevel SLIM technology. Ion trajectory simulations were used to optimize SLIM board spacings and SLIM board thicknesses, and a new method of efficiently transferring ions between SLIM levels using asymmetric traveling waves (TWs) was demonstrated. We experimentally characterized the performance of the miniSLIM IMS-MS relative to a drift tube IMS-MS using Agilent tuning mixture cations and tetraalkylammonium cations. The miniSLIM achieved a resolving power of up to 131 (CCS/ΔCCS), which is ∼1.5× higher than achievable with a 78 cm path length drift tube IMS. Additionally, the entire ion mobility range was successfully transmitted in a single separation. We also demonstrated the miniSLIM’s performance as a standalone IMS system (i.e., without MS), which showed baseline separation between all AgTM cations and a clear differentiation between different charge states of a standard peptide mixture. Overall, the miniSLIM provides a compact alternative to high performance IMS instruments possessing similar path lengths.

We evaluated the effect of four different waveform profiles (Square, Sine, Triangle, and asymmetric Sawtooth) on the accuracy of collision cross section (CCS) measurements using traveling wave ion mobility spectrometry (TWIMS) separations in structures for lossless ion manipulations (SLIM). The effects of the waveform profiles on the accuracy of the CCS measurements were evaluated for four classes of compounds (lipids, peptides, steroids, and nucleosides) at different TW speeds (126–206 m/s) and amplitudes (15–89 V). For the lipids and peptides, the TWIMS-based CCS (TWCCS) deviations from the corresponding drift-tube-based CCS (DTCCS) measurements were significantly lower in experiments conducted using the Sawtooth waveform compared to the square waveform. This observation can be rationalized by the lower maximum electric field experienced by ions with a Sawtooth waveform, as compared to the other waveforms, resulting in a lower probability for significant ion heating. We also observed that given approximately comparable resolution for all four waveforms, the Sawtooth waveform resulted in lower TWCCS error and a better agreement with DTCCS values than the Square waveform. In addition, for the steroids and nucleosides, an opposite TWCCS trend was observed, with higher errors with the Sawtooth waveform and lower with the Square waveform, suggesting that these molecules tend to become slightly more compact under ion heating conditions. Under optimum conditions, all TWCCS measurements on the SLIM platform were within 0.5% of those measured in the drift tube ion mobility spectrometry.