An atmospheric pressure ion funnel with a slit entrance for enhancing signal and resolution in high resolution differential ion mobility mass spectrometry

Abstract

Differential ion mobility (DMS) is a versatile ion separation method that is often integrated with mass spectrometry (MS). In DMS, extremely high electric fields are used such that ion mobility depends non-linearly on electric field and thus, ion separations can be more orthogonal to MS than lower field ion mobility-based methods. DMS can have sufficiently high resolution to be used for enantiomer analysis of small molecules and to separate protein ions with peak widths comparable to those obtained for peptides. However, the performance of high resolution DMS-MS can be limited owing to the substantial loss of ions (>10-fold) that can occur upon their transfer from atmospheric pressure (where DMS separation typically occurs) to vacuum through a narrow conductance limited inlet (e.g. capillary) to the MS. Here, results from simulated ion trajectory simulations suggest that in high resolution DMS most ions can be lost by ‘crashing’ onto the narrow capillary inlet after exiting the DMS separation channel. To enhance DMS sensitivity and resolving power, an integrated DMS-MS interface concept is reported that consists of a slit electrode and a 12-electrode atmospheric pressure ion funnel (APIF). By using an APIF with slit entrance, the simulated ion transmission efficiencies increase by up to 257% for singly charged ions ([DMMP + H]⁺, [tryptophan + H]⁺, and [(2-dodecanone)₂ + H]⁺) and by 209% for [ubiquitin + 12H]¹²⁺, without compromising resolving power. The use of APIF improves the ion focussing from the DMS exit to the MS capillary to improve sensitivity, and the slit ensures that ion dispersion in the analytically relevant direction perpendicular to the DMS electrodes is restricted to enhance resolution. By narrowing the slit of the DMS-Slit-APIF interface, the DMS resolving power can be increased further by at least 20%. Overall, these results indicate that the integrated DMS-Slit-APIF interface is promising for improving the sensitivity and resolution for many different types of DMS-MS experiments.