Enhancing Biological LC-MS Analyses Using Ion Mobility Spectrometry

Abstract

Liquid chromatography coupled with mass spectrometry (LC-MS) is a very sensitive and selective technique for both unknown identification and compound quantification. However, because of biological sample complexity (e.g., chemical background, isomeric interferences), the use of ion mobility to provide additional separation capabilities is becoming increasingly common. Gas-phase ion mobility devices separate ions based on ion–neutral interactions, and therefore peak capacity for an LC-MS analysis is enhanced by ion mobility since separation is complementary to both LC and MS. Basic principles of common ion mobility techniques used in commercial ion mobility MS instrumentation are presented. Six commercial ion mobility devices are discussed, and these have been broadly classified as either selective or dispersive. The three dispersive instruments described include two time-based and one field-based device, and these relate ion mobility to ion properties such as collision cross section. The use of dispersive ion mobility devices is growing rapidly, especially in nontargeted analysis and within omics workflows, in particular. Conversely, the three selective ion mobility devices that are discussed separate ions based on changes in ion mobility (differential mobility spectrometry, DMS). Since DMS acts as an ion filter, it has been widely used in LC-MS quantification. Although, DMS has been shown to provide a more orthogonal separation to MS compared with conventional ion mobility spectrometry, slower acquisition speeds have inhibited nontargeted applications until recently. This chapter describes differences among these commercial instruments and highlights primary application areas of ion mobility with LC-MS showing select examples for both targeted and nontargeted biological applications.