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. When sampling continuous ion sources the temporal sampling or the incoming ion beam is often achieved by the electronic modulation of a grid or electric field. Not surprisingly, the rate at which a given ion population traverses this gating region is directly proportional to an ion's population and the applied electric field. This scenario establishes conditions where discrimination of the incoming ion beam may occur when the ion gate modulation rate is minimized. Recent developments in the mechanical construction of ion gates and their subsequent operation suggest that the mobility discrimination during ion gating may be minimized, however, it is remains unclear how this behavior will translate to ion beam multiplexing approaches. In this present work, we compare the performance levels of the tri-state ion shutter (3S-IS) to the two-state ion shutter (2S-IS) using a series of Fourier transform ion mobility mass spectrometry (FT-IMMS) experiments. The performance of the two different shutter operating principles were evaluated using ion multiplexing using tetraalkylammonium salts (TXA ions; T5-T8, T10, T12) bradykinin, and a set of reversed sequence isomeric pentapeptides using a variety of different ion gate frequency sweeps. Noticeable increases in ion throughput were observed for the 3S-IS with 95% and 45% increases in ion counts for the T5 and T12 ions respectively compared to the 2S-IS. Similarly, a 27% and 55% increase in ion counts was observed for the M + 2H
2+
and M + H
+
ions of bradykinin, respectively. In addition, a 10% increase in resolving power was also observed for the 3S-IS compared to the 2S-IS. Overall, utilization of the 3S-IS effectively minimizes both discrimination of slower ions and the impact of gate depletion effect common to traditional ion gating techniques.
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.
Using Fourier-Transform ion gate modulation technique, we compare the ability of the tri-state ion shutter (3S-IS) to the two-state ion shutter (2S-IS) in separating three pairs of isomeric peptide ...including 1.Gly-Arg-Gly-Asp-Ser (GRGDS) / Ser-Asp-Gly-Arg-Gly (SDGRG); 2.Sar-Arg-Gly-Asp-Ser-Pro (SRGDSP) / Gly-Arg-Gly-Asp-Thr-Pro (GRGTP); 3.Kemptide / (Val
6
, Ala
7
)-Kemptide using electrospray ionization and ion mobility spectrometry. Mobility separation was evaluated for peptide individually and as simple mixtures. Baseline resolution of both singly and doubly charged ions of the isomeric pentapeptide mixture of GRGDS / SDGRG was attainable with the described IMS system using the 3S-IS configuration, illustrating the capacity of the present instrument to resolve isomeric compounds with differences in ion neutral collision cross section (CCS) of less than 1% for the singly charged ions. However, with the 2S-IS, both singly and doubly charged ions of the same peptide mixture were unresolved in the mobility domain. To our knowledge, this is the first-time baseline separation has been reported for the singly charged ions of the isomeric reversed sequence pentapeptide mixture using Fourier transformed drift tube IMS with nitrogen as the drift gas. For all the peptide mixtures, the ion counts for the ion mixture recorded with the 3S-IS were substantially higher (> 50%) in comparison to the 2S-IS. The resolving power of the instrument ranged between 82 to 128 for the target analyte ions analyzed in a mixture using the 3S-IS. Whereas, the resolving power of the 2S-IS ranged between 60 and 100 for the target analytes. Overall, a 20% increase in resolving power was obtained with the 3S-IS in comparison to the 2S-IS. Separation of the different isomeric peptide ion mixture depicted in this present study clearly shows the unique size-to-charge separation ability of IMS that complements the mass-to-charge ratio measurement capacity of mass spectrometry.
Vapor assisted mobility shift measurements were made with atmospheric pressure drift-tube ion mobility–mass spectrometry (IM–MS) to determine the thermodynamic properties of weakly bound ion–molecule ...clusters formed from protonated phenylalanine and neutral vapor molecules with hydroxyl functional groups. Relative binding energies and gas-phase association energies of amino acid ions clustered with small organic molecules have been established previously using high-pressure mass spectrometry. However, the issue of volatility largely prohibits the use of high-pressure mass spectrometry for the determination of gas-phase associations of amino acid ions clustered with neutral vapor molecules in many instances. In contrast, ion mobility measurements can be made at atmospheric pressure with volatile vapor additives near and above their boiling points, providing access to clustering equilibria not possible using high-vacuum techniques. In this study, we report the gas-phase association energies, enthalpies, and entropies for a protonated phenylalanine ion clustered with three neutral vapor molecules: 2-propanol, 1-butanol, and 2-pentanol based upon measurements at temperatures ranging from 120 to 180 °C. The gas-phase enthalpy and entropy changes ranged between −4 to −7 kcal/mol and −3 to 6 cal/(mol K), respectively. We found enthalpically favored ion–neutral cluster reactions for phenylalanine with entropic barriers for the formation of phenylalanine–1-butanol and phenylalanine–2-pentanol cluster ions, while phenylalanine–2-propanol cluster ion formation is both enthalpically and (weakly) entropically favorable. Under the measurement conditions examined, phenylalanine–vapor modifier cluster ion formation is clearly observed via shifts in the drift time for the three test vapor molecules. In comparison, negligible shifts in mobility are observed for protonated arginine exposed to the same vapor modifiers.
Ion Mobility Separations Using Cocentric Architecture Kwantwi-Barima, Pearl; Hollerbach, Adam L.; Attah, Isaac K. ...
Journal of the American Society for Mass Spectrometry,
07/2024, Letnik:
35, Številka:
7
Journal Article
Recenzirano
Ion mobility separations, especially using drift tube ion mobility spectrometers, are usually performed in linear channels, which can have a large footprint when extended to achieve higher resolving ...powers. In this work, we explored the performance of an ion mobility device with a curved architecture, which can have a more compact form. The cocentric ion mobility spectrometer (CoCIMS) manipulates ions between two cocentric surfaces containing a serpentine track. The mobility separation inside the CoCIMS is achieved using traveling waveforms (TWs). We initially evaluated the device using ion trajectory simulations using SIMION, which indicated that when ions traveled circularly inside the CoCIMS they resulted in similar resolving powers and transmitted m/z range as traveling in a straight path. We then performed experimental validation of the CoCIMS in conjunction with a TOF MS. The CoCIMS was made of two flexible printed circuit board materials folded into cocentric cylinders separated by a gap of 2.8 mm. The device was about 50 mm diameter ×152 mm long and provided 1.846 m of serpentine path length. Three sets of mixtures (Agilent tune mixture, tetraalkylammonium salts, and an eight-peptide mixture) and four traveling waveform profiles (square, sine, triangle, and sawtooth) were used. The sawtooth TW profile produced a slightly higher resolving power for the Agilent tuning mixture and tetraalkylammonium ions. The average resolving power for Agilent tune mixture ions ranged from 37 (using sawtooth TW) to 27 (using square TW). The average resolving powers ranged from 45 (sawtooth TW) to 31 (square TW) for tetraalkylammonium ions. The resolving power of the peptide mixture ions was similar among the four TW profiles and ranged from 51 to 56. The average percent error in TWCCS for the peptide mixture ions was about 0.4%. The new device showed promising results, but improvements are needed to further increase the resolving power.
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.
The accumulation of very large ion populations in traveling wave (TW)-based Structures for Lossless ion Manipulations (SLIM) has been studied to better understand aspects of “in-SLIM” ion ...accumulation, and particularly its use in conjunction with ion mobility spectrometry (IMS). A linear SLIM ion path was implemented that had a “gate” for blocking and accumulating ions for arbitrary time periods. Removing the gate potential caused ions to exit, and the spatial distributions of accumulated ions examined. The ion populations for a set of peptides increased approximately linearly with increased accumulation times until space change effects became significant, after which the peptide precursor ion populations decreased due to growing space charge-related ion activation, reactions, and losses. Ion activation increased with added storage times and the TW amplitude. Lower amplitude TWs in the accumulation/storage region prevented or minimized ion losses or ion heating effects that can also lead to fragmentation. Our results supported the use of an accumulation region close to the SLIM entrance for speeding accumulation, minimizing ion heating, and avoiding ion population profiles that result in IMS peak tailing. Importantly, space charge-driven separations were observed for large populations of accumulated species and attributed to the opposing effects of space charge and the TW. In these separations, ion species form distributions or peaks, sometimes moving against the TW, and are ordered in the SLIM based on their mobilities. Only the highest mobility ions located closest to the gate in the trapped ion population (and where the highest ion densities were achieved) were significantly activated. The observed separations may offer utility for ion prefractionation of ions and increasing the dynamic range measurements, increasing the resolving power of IMS separations by decreasing peak widths for accumulated ion populations, and other purposes benefiting from separations of extremely large ion populations.
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 cm2 V–1s–1 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 cm2V–1s–1) compared the DMMP monomer (1.63 cm2V–1s–1). Meanwhile, the DMMP dimer experienced no change in mobility (1.45 cm2V–1s–1). 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.
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.
Structures for lossless ion manipulations (SLIM) technology has demonstrated high resolving power ion mobility separation and flexibility to integrate complex ion manipulations into a single ...experimental platform. To enable IMS separations, trapping/accumulating ions inside SLIM (or in-SLIM) prior to injection of a packet for separations provides ease of operation and reduces the need for dedicated ion traps external to SLIM. To fully characterize the ion accumulation process, we have evaluated the effect of TW amplitudes, ion collection times, and storage times on the "in-SLIM" accumulation process. The study utilized a SLIM module comprising 5 distinct tracks, each with a specific ion accumulation configuration. The effect of the TW conditions on the accumulation process was investigated for a 3-peptide mixture: kemptide, angiotensin II, and neurotensin at a TW speed of 106 m/s. The effect of ion accumulation time/collection time and storage time was investigated, in addition to TW amplitude. Overall, the signal of the analyte ions increased when the ion collection time increased from 49 to 163 ms but decreased when the ion collection time increased further to 652 ms due to the space charge effects. Ion losses were observed at high TW amplitudes (e.g., 15 V
and 20 V
). In addition, under space charge conditions (e.g., collection times of 163 and 652 ms), the signal of the analyte ions decreased with an increase in storage times for all TW amplitudes applied to the trapping region. For ion accumulation, the data indicate that gentler TW conditions must be utilized to minimize ion losses and fragments to benefit from the "in-SLIM" accumulation process. Wider SLIM tracks provided better performance than those with narrower tracks.
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.
