Sandilya V. B. Garimella

Experimental Evaluation and Optimization of Structures for Lossless Ion Manipulations for Ion Mobility Spectrometry with Time-of-Flight Mass Spectrometry

We report on the performance of structures for lossless ion manipulation (SLIM) as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM, demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central “rung” electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2–6 V) and RF amplitude (≥160 Vp-p at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a significant range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning RF on the rung electrodes and DC on the guard electrodes. However, both resolving power and ion transmission showed a dependence on these voltages, and the best conditions for both were >300 Vp-p RF (685 kHz) and 7–11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R ∼ 58), showing that degraded resolution from a “racetrack” effect from turning around a corner can be successfully avoided, and the capability also was maintained for essentially lossless ion transmission.

Ion Trapping, Storage, and Ejection in Structures for Lossless Ion Manipulations

A new Structures for Lossless Ion Manipulations (SLIM) module, having electrode arrays patterned on a pair of parallel printed circuit boards (PCB), was constructed and utilized to investigate capabilities for ion trapping at a pressure of 4 Torr. Positive ions were confined by application of RF voltages to a series of inner rung electrodes with alternating phase on adjacent electrodes, in conjunction with positive DC potentials on surrounding guard electrodes on each PCB. An axial DC field was also introduced by stepwise varying the DC potentials applied to the inner rung electrodes to control the ion transport and accumulation inside the ion trapping region. We show that ions can be trapped and accumulated with up to 100% efficiency, stored for at least 5 h with no significant losses, and then could be rapidly ejected from the SLIM trap. The present results provide a foundation for the development of much more complex SLIM devices that facilitate extended ion manipulations.

Simulation of electric potentials and ion motion in planar electrode structures for lossless ion manipulations (SLIM).

AbstractWe report a conceptual study and computational evaluation of novel planar electrode structures for lossless ion manipulations (SLIM). Planar electrode SLIM components were designed that allow for flexible ion confinement, transport, and storage using a combination of radio frequency (rf) and DC fields. Effective potentials can be generated that provide near ideal regions for confining and manipulating ions in the presence of a gas. Ion trajectory simulations using SIMION 8.1 demonstrated the capability for lossless ion motion in these devices over a wide m/z range and a range of electric fields at low pressures (e.g., a few Torr). More complex ion manipulations (e.g., turning ions by 90o and dynamically switching selected ion species into orthogonal channels) are also shown feasible. The performance of SLIM devices at ~4 Torr pressure for performing ion mobility-based separations (IMS) is computationally evaluated and compared with initial experimental results, and both are also shown to agree closely with experimental and theoretical IMS performance for a conventional drift tube design. Graphical Abstractᅟ

Characterization of Ion Dynamics in Structures for Lossless Ion Manipulations

Structures for Lossless Ion Manipulation (SLIM) represent a novel class of ion optical devices based upon electrodes patterned on planar surfaces, and relying on a combined action of radiofrequency and DC electric fields and specific buffer gas density conditions. Initial experimental studies have demonstrated the feasibility of the SLIM concept. This report offers an in-depth consideration of key ion dynamics properties in such devices based upon ion optics theory and computational modeling. The SLIM devices investigated are formed by two surfaces, each having an array of radiofrequency (RF) “rung” electrodes, bordered by DC “guard” electrodes. Ion motion is confined by the RF effective potential in the direction orthogonal to the boards and limited or controlled in the transversal direction by the guard DC potentials. Ions can be efficiently trapped and stored in SLIM devices where the confinement of ions can be “soft” in regard to the extent of collisional activation, similarly to RF-only multipole ion guides and traps. The segmentation of the RF rung electrodes and guards along the axis makes it possible to apply static or transient electric field profiles to stimulate ion transfer within a SLIM. In the case of a linear DC gradient applied to RF rungs and guards, a virtually uniform electric field can be created along the axis of the device, enabling high quality ion mobility separations.

Characterization of Traveling Wave Ion Mobility Separations in Structures for Lossless Ion Manipulations

We report on the development and characterization of a traveling wave (TW)-based Structures for Lossless Ion Manipulations (TW-SLIM) module for ion mobility separations (IMS). The TW-SLIM module uses parallel arrays of rf electrodes on two closely spaced surfaces for ion confinement, where the rf electrodes are separated by arrays of short electrodes, and using these TWs can be created to drive ion motion. In this initial work, TWs are created by the dynamic application of dc potentials. The capabilities of the TW-SLIM module for efficient ion confinement, lossless ion transport, and ion mobility separations at different rf and TW parameters are reported. The TW-SLIM module is shown to transmit a wide mass range of ions (m/z 200-2500) utilizing a confining rf waveform (∼1 MHz and ∼300 Vp-p) and low TW amplitudes (<20 V). Additionally, the short TW-SLIM module achieved resolutions comparable to existing commercially available low pressure IMS platforms and an ion mobility peak capacity of ∼32 for TW speeds of <210 m/s. TW-SLIM performance was characterized over a wide range of rf and TW parameters and demonstrated robust performance. The combined attributes of the flexible design and low voltage requirements for the TW-SLIM module provide a basis for devices capable of much higher resolution and more complex ion manipulations.

Mobility-Selected Ion Trapping and Enrichment Using Structures for Lossless Ion Manipulations

The integration of ion mobility spectrometry (IMS) with mass spectrometry (MS) and the ability to trap ions in IMS-MS measurements is of great importance for performing reactions, accumulating ions, and increasing analytical measurement sensitivity. The development of Structures for Lossless Ion Manipulations (SLIM) offers the potential for ion manipulations in an extended and more effective manner, while opening opportunities for many more complex sequences of manipulations. Here, we demonstrate an ion separation and trapping module and a method based upon SLIM that consists of a linear mobility ion drift region, a switch/tee and a trapping region that allows the isolation and accumulation of mobility-separated species. The operation and optimization of the SLIM switch/tee and trap are described and demonstrated for the enrichment of the low abundance ions. A linear improvement in ion intensity was observed with the number of trapping/accumulation events using the SLIM trap, illustrating its potential for enhancing the sensitivity of low abundance or targeted species.

Achieving High Resolution Ion Mobility Separations Using Traveling Waves in Compact Multiturn Structures for Lossless Ion Manipulations

We report on ion mobility (IM) separations achievable using traveling waves (TW) in a Structures for Lossless Ion Manipulations (SLIM) module having a 44 cm path length and 16 90° turns. The performance of the TW-SLIM module was evaluated for ion transmission and IM separations with different RF, TW parameters, and SLIM surface gaps in conjunction with mass spectrometry. In this work, TWs were created by the transient and dynamic application of DC potentials. The module demonstrated highly robust performance and, even with 16 closely spaced turns, achieving IM resolution performance and ion transmission comparable to a similar straight path module. We found an IM peak capacity of ∼31 and peak generation rate of 780 s(-1) for TW speeds of ∼80 m/s using the current multi-turn TW-SLIM module. The separations achieved for isomers of peptides and tetrasaccharides were found to be comparable to those from a ∼0.9-m drift tube-based IM-MS platform operated at the same pressure (4 Torr). The combined attributes of flexible design, low voltage requirements and lossless ion transmission through multiple turns for the present TW-SLIM module provides a basis for SLIM devices capable of achieving much greater IM resolution via greatly extended ion path lengths and using compact serpentine designs.

Improving Ion Mobility Measurement Sensitivity by Utilizing Helium in an Ion Funnel Trap

Ion mobility instruments that utilize nitrogen as buffer gas are often preceded by an ion trap and accumulation region that also uses nitrogen, and for different inert gases, no significant effects upon performance are expected for ion mobility spectrometry (IMS) of larger ions. However, we have observed significantly improved performance for an ion funnel trap upon adding helium; the signal intensities for higher m/z species were improved by more than an order of magnitude compared to using pure nitrogen. The effect of helium upon IMS resolving power was also studied by introducing a He/N2 gas mixture into the drift cell, and in some cases, a slight improvement was observed compared to pure N2. The improvement in signal can be largely attributed to faster and more efficient ion ejection into the drift tube from the ion funnel trap.

Spatial Ion Peak Compression and its Utility in Ion Mobility Spectrometry

AbstractA novel concept for ion spatial peak compression is described, and discussed primarily in the context of ion mobility spectrometry (IMS). Using theoretical and numerical methods, the effects of using non-constant (e.g., linearly varying) electric fields on ion distributions (e.g., an ion mobility peak) is evaluated both in the physical and temporal domains. The application of a linearly decreasing electric field in conjunction with conventional drift field arrangements is shown to lead to a reduction in IMS physical peak width. When multiple ion packets (i.e., peaks) in a selected mobility window are simultaneously subjected to such fields, there is ion packet compression (i.e., a reduction in peak widths for all species). This peak compression occurs with only a modest reduction of resolution, which can be quickly recovered as ions drift in a constant field after the compression event. Compression also yields a significant increase in peak intensities. Ion mobility peak compression can be particularly useful for mitigating diffusion-driven peak broadening over very long path length separations (e.g., in cyclic multi-pass arrangements), and for achieving higher S/N and IMS resolution over a selected mobility range. Graphical Abstractᅟ

Rapid Ion Mobility Separations of Bile Acid Isomers Using Cyclodextrin Adducts and Structures for Lossless Ion Manipulations

Bile acids (BAs) constitute an important class of steroid metabolites often displaying changes associated with disease states and other health conditions. Current analyses for these structurally similar compounds are limited by a lack of sensitivity and long separation times with often poor isomeric resolution. To overcome these challenges and provide rapid analyses for the BA isomers, we utilized cyclodextrin adducts in conjunction with novel ion mobility (IM) separation capabilities provided by structures for lossless ion manipulations (SLIM). Cyclodextrin was found to interact with both the tauro- and glyco-conjugated BA isomers studied, forming rigid noncovalent host-guest inclusion complexes. Without the use of cyclodextrin adducts, the BA isomers were found to be nearly identical in their respective mobilities and thus unable to be baseline resolved. Each separation of the cyclodextrin-bile acid host-guest inclusion complex was performed in less than 1 s, providing a much more rapid alternative to current liquid chromatography-based separations. SLIM provided capabilities for the accumulation of larger ion populations and IM peak compression that resulted in much higher resolution separations and increased signal intensities for the BA isomers studied.