Ion filters based on planar DMS can be integrated with the inlet configuration of most mass spectrometers, and are able to enhance the quality of mass analysis and quantitative accuracy by reducing chemical noise, and by pre-separating ions of similar mass. This paper is the first in a series of three papers describing the optimization of DMS / MS instrumentation. In this paper the important physical parameters of a planar DMS-MS interface including analyzer geometry, analyzer coupling to a mass spectrometer, and transport gas flow control are considered. The goal is to optimize ion transmission and transport efficiency, provide optimal and adjustable resolution, and produce stable operation under conditions of high sample contamination. We discuss the principles of DMS separations and highlight the theoretical underpinnings. The main differences between planar and cylindrical geometries are presented, including a discussion of the advantages and disadvantages of RF ion focusing. In addition, we present a description of optimization of the frequency and amplitude of the DMS fields for resolution and ion transmission, and a discussion of the influence and importance of ion residence time in DMS. We have constructed a mass spectrometer interface for planar geometries that takes advantage of atmospheric pressure gas dynamic principles, rather than ion focusing, to minimize ion losses from diffusion in the analyzer and to maximize total ion transport into the mass spectrometer. A variety of experimental results has been obtained that illustrate the performance of this type of interface, including tests of resistance to high contamination levels, and the separation of stereoisomers. In a subsequent publication the control of the chemical interactions that drive the separation process of a DMS / MS system will be considered. In a third publication we describe novel electronics designed to provide the high voltages asymmetric waveform fields (SV) required for these devices as well as the effects of different waveforms.

This review of atmospheric pressure ion sources discusses major developments that have occurred since 1991. Advances in the instrumentation and understanding of the key physical principles are the primary focus. Developments with electrospray and atmospheric pressure chemical ionization and variations encompassing adaptations for surface analysis, ambient air analysis, high throughput, and modification of the ionization mechanism are covered. An important and limiting consequence of atmospheric pressure chemical ionization, chemical noise, is discussed as is techniques being employed to ameliorate the problem. Ion transfer and transport from atmospheric pressure into deep vacuum is an area undergoing constant improvement and refinement so is given considerable consideration in this review.

This review of differential mobility spectrometry focuses primarily on mass spectrometry coupling, starting with the history of the development of this technique in the Soviet Union. Fundamental principles of the separation process are covered, in addition to efforts related to design optimization and advancements in computer simulations. The flexibility of differential mobility spectrometry design features is explored in detail, particularly with regards to separation capability, speed, and ion transmission. 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:687-737, 2016.

In differential mobility spectrometry (DMS, also referred to as high field asymmetric waveform ion mobility spectrometry, FAIMS), ions are separated on the basis of the difference in their mobility under high and low electric fields. The addition of polar modifiers to the gas transporting the ions through a DMS enhances the formation of clusters in a field-dependent way and thus amplifies the high and low field mobility difference resulting in increased peak capacity and separation power. Observations of the increase in mobility field dependence are consistent with a cluster formation model, also referred to as the dynamic cluster-decluster model. The uniqueness of chemical interactions that occur between an ion and cluster-forming neutrals increases the selectivity of the separation and the depression of low-field mobility relative to high-field mobility increases the compensation voltage and peak capacity. The effect of polar modifiers on the peak capacity across a broad range of chemicals has been investigated. We discuss the theoretical underpinnings which explain the observed effects. In contrast to the result from polar modifiers, we find that using mixtures of inert gases as the transport gas improve resolution by reducing peak width but has very little effect on peak capacity or selectivity. Inert gases do not cluster and thus do not reduce low field mobility relative to high-field mobility. The observed changes in the differential mobility α parameter exhibited by different classes of compounds when the transport gas contains polar modifiers or has a significant fraction of inert gas can be explained on the basis of the physical mechanisms involved in the separation processes.

Here, we present the separation of two ions that differ only by the site of protonation of the analyte molecule using differential mobility spectrometry (DMS). Protonated 4-aminobenzoic acid molecules (4-ABA) generated by positive-mode electrospray ionization [ESI(+)] can exist with the proton residing on either the amine nitrogen (N-protonated) or the carboxylic acid oxygen (O-protonated), and the protonation site can differ on the basis of the solvent system used. In this study, we demonstrate the identification and separation of N- and O-protonated 4-ABA using DMS, with structural assignments verified by: (1) the presence of distinct peaks in the DMS ionogram, (2) the observed effects resulting from altering the ESI(+) solvent system, (3) the observed (13)C NMR chemical shifts arising from altering the solvent system, (4) the observation of distinct MS/MS fragmentation patterns for the two DMS-separated ions, (5) the unique hydrogen-deuterium exchange behavior for these ions, and (6) the fundamental behavior of these two ions within the DMS cell, linked back to the structural differences between the two protonated forms.