Randolph V. Norheim

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.

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.

Serpentine Ultralong Path with Extended Routing (SUPER) High Resolution Traveling Wave Ion Mobility-MS using Structures for Lossless Ion Manipulations

Ion mobility (IM) separations have a broad range of analytical applications, but insufficient resolution often limits their utility. Here, we report on ion mobility separations in a structures for lossless ion manipulations (SLIM) serpentine ultralong path with extended routing (SUPER) traveling wave (TW) ion mobility (IM) module in conjunction with mass spectrometry (MS). Ions were confined in the SLIM by rf fields in conjunction with a DC guard bias, enabling essentially lossless TW transmission over greatly extended paths. The extended routing utilized multiple passes (e.g., ∼1094 m over 81 passes through the 13.5 m serpentine path) and was facilitated by the introduction of a lossless ion switch that allowed ions to be directed to either the MS detector or for another pass through the serpentine separation region, allowing theoretically unlimited IM path lengths. The multipass SUPER IM-MS provided resolution approximately proportional to the square root of the number of passes (or total path length). More than 30-fold higher IM resolution (∼340 vs ∼10) for Agilent tuning mix m/z 622 and 922 ions was achieved for 40 passes compared to commercially available drift tube IM and other TWIM-based platforms. An initial evaluation of the isomeric sugars lacto-N-hexaose and lacto-N-neohexaose showed the isomeric structures to be baseline resolved, and a new conformational feature for lacto-N-neohexaose was revealed after 9 passes. The new SLIM SUPER high resolution TWIM platform has broad utility in conjunction with MS and is expected to enable a broad range of previously challenging or intractable separations.

Development of an Ion Mobility Spectrometry-Orbitrap Mass Spectrometer Platform

Complex samples benefit from multidimensional measurements where higher resolution enables more complete characterization of biological and environmental systems. To address this challenge, we developed a drift tube-based ion mobility spectrometry-Orbitrap mass spectrometer (IMS-Orbitrap MS) platform. To circumvent the time scale disparity between the fast IMS separation and the much slower Orbitrap MS acquisition, we utilized a dual gate and pseudorandom sequences to multiplex the injection of ions and allow operation in signal averaging (SA), single multiplexing (SM), and double multiplexing (DM) IMS modes to optimize the signal-to-noise ratio of the measurements. For the SM measurements, a previously developed algorithm was used to reconstruct the IMS data. A new algorithm was developed for the DM analyses involving a two-step process that first recovers the SM data and then decodes the SM data. The algorithm also performs multiple refining procedures to minimize demultiplexing artifacts. The new IMS-Orbitrap MS platform was demonstrated by the analysis of proteomic and petroleum samples, where the integration of IMS and high mass resolution proved essential for accurate assignment of molecular formulas.

Rectangular Ion Funnel: A New Ion Funnel Interface for Structures for Lossless Ion Manipulations

Structures for lossless ion manipulations (SLIM) have recently demonstrated the ability for near lossless ion focusing, transfer, and trapping in subatmospheric pressure regions. While lossless ion manipulations are advantageously applied to the applications of ion mobility separations and gas phase reactions, ion introduction through ring electrode ion funnels or more conventional ion optics to SLIM can involve discontinuities in electric fields or other perturbations that result in ion losses. In this work, we developed and investigated a new funnel design that aims to seamlessly couple to SLIM at the funnel exit. This rectangular ion funnel (RIF) was initially evaluated by ion simulations, fabricated utilizing printed circuit board technology, and tested experimentally. The RIF was integrated to a SLIM-time of flight (TOF) MS system, and the operating parameters, including RF, DC bias of the RIF electrodes, and electric fields for effectively interfacing with a SLIM, were characterized. The RIF provided a 2-fold sensitivity increase without significant discrimination over a wide m/z range and well matched to that of SLIM, along with greatly improved SLIM operational stability.

Enhancing biological analyses with three dimensional field asymmetric ion mobility, low field drift tube ion mobility and mass spectrometry (μFAIMS/IMS-MS) separations

Multidimensional high throughput separations are ideal for analyzing distinct ion characteristics simultaneously in one analysis. We report on the first evaluation of a platform coupling a high speed field asymmetric ion mobility spectrometry microchip (μFAIMS) with drift tube ion mobility and mass spectrometry (IMS-MS). The μFAIMS/IMS-MS platform was used to analyze biological samples and simultaneously acquire multidimensional FAIMS compensation fields, IMS drift times, and accurate ion masses for the detected features. These separations thereby increased the overall measurement separation power, resulting in greater information content and more complete characterization of the complex samples. The separation conditions were optimized for sensitivity and resolving power by the selection of gas compositions and pressures in the FAIMS and IMS separation stages. The resulting performance provided three dimensional separations, benefitting both broad complex mixture studies and targeted analyses by improving isomeric separations and allowing detection of species obscured by interfering peaks.

Improved ion optics for introduction of ions into a 9.4-T Fourier transform ion cyclotron resonance mass spectrometer.

Enhancements to the ion source and transfer optics of our 9.4 T Fourier transform ion cyclotron resonance (ICR) mass spectrometer have resulted in improved ion transmission efficiency for more sensitive mass measurement of complex mixtures at the MS and MS/MS levels. The tube lens/skimmer has been replaced by a dual ion funnel and the following octopole by a quadrupole for reduced ion cloud radial expansion before transmission into a mass-selective quadrupole. The number of ions that reach the ICR cell is increased by an order of magnitude for the funnel/quadrupole relative to the tube lens/skimmer/octopole.