Ion mobility spectrometry—mass spectrometry performance using electrodynamic ion funnels and elevated drift gas pressures

Abstract

The ability of ion mobility spectrometry coupled with mass spectrometry (IMS-MS) to characterize biological mixtures has been illustrated over the past eight years. However, the challenges posed by the extreme complexity of many biological samples have demonstrated the need for higher resolution IMS-MS measurements. We have developed a higher resolution ESI-IMS-TOF MS by utilizing high-pressure electrodynamic ion funnels at both ends of the IMS drift cell and operating the drift cell at an elevated pressure compared with that conventionally used. The ESI-IMS-TOF MS instrument consists of an ESI source, an hourglass ion funnel used for ion accumulation/injection into an 88 cm drift cell, followed by a 10 cm ion funnel and a commercial orthogonal time-of-flight mass spectrometer providing high mass measurement accuracy. It was found that the rear ion funnel could be effectively operated as an extension of the drift cell when the DC fields were matched, providing an effective drift region of 98 cm. The resolution of the instrument was evaluated at pressures ranging from 4 to 12 torr and ion mobility drift voltages of 16 V/cm (4 torr) to 43 V/cm (12 torr). An increase in resolution from 55 to 80 was observed from 4 to 12 torr nitrogen drift gas with no significant loss in sensitivity. The choice of drift gas was also shown to influence the degree of ion heating and relative trapping efficiency within the ion funnel. eveloping an effective analytical method to characterize extremely complex biological systems is one of the most difficult challenges in analytical chemistry. While many methods have been explored for this purpose, the high throughput capabilities of mass spectrometry (MS) and its ability to directly sample biomolecules out of solution using electrospray ionization (ESI) [1] are particularly suited to this task. Despite advances in this field, due to the broad range of analytes and their varying signal intensities within a complex sample, the ability to comprehensively detect a wide dynamic range of analytes in a single analysis remains limited. To address this problem, various separation methods capable of fractionation before MS analysis have been employed [2,3], specifically liquid chromatography (LC) [4] and ion mobility spectrometry (IMS) [5][6][7]. Thus, the methods of LC-MS [4], IMS-MS [8,9], and even LC-IMS-MS [10,11] have all been utilized in analyzing biological samples.While LC-MS allows analysis of the retention time and m/z for each biomolecule in a sample [12,13], a significant limitation to this technique is its speed since separations may take from minutes to several hours. On the other hand, IMS offers the basis for much faster separations when coupled with MS [8,9]. IMS is based on the fact that species with different collision cross sections travel with different velocities (i.e., ion mobilities) when they are pulled by a weak electric field through a drift cell filled with a buffer gas [14]. By coupling IMS to TOF MS, samples can be separated based on size and m/z very quickly due to ...

Conformational Distribution of Bradykinin [bk + 2 H]2+ Revealed by Cold Ion Spectroscopy Coupled with FAIMS

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Gas-Phase Hydrogen-Deuterium Exchange Labeling of Select Peptide Ion Conformer Types: a Per-Residue Kinetics Analysis

“…The development of IMS instrumentation [20,[33][34][35][36][37][38][39][40], theory [41][42][43][44][45], and applications [46][47][48][49][50] is described in the literature. Here, only a brief description of the IMS-MS instrument and its operation is presented.…”

Increased Sensitivity in Proton Transfer Reaction Mass Spectrometry by Incorporation of a Radio Frequency Ion Funnel

“…This suggests that it might be possible to construct a compact drift tube which can simultaneously operate as an ion funnel and as an ion-molecule reaction vessel with a fixed reaction time. This idea has been proposed and demonstrated previously in the context of ion mobility spectrometry 23 but not for PTR-MS. In this paper we describe a prototype design and explore its initial application in PTR-MS. An improvement in the detection sensitivity of between one and two orders of magnitude is observed for most of the test gases, which suggests that the RF ion funnel/drift tube may significantly enhance the performance of PTR-MS.…”