ABSTRACT
True Mobility ................................................................................................ 107 5.3 Advantages and Limitations of DMAs ......................................................... 108
5.3.1 Resolution versus Transmission ........................................................ 109 5.3.2 Duty Cycle ........................................................................................ 109 5.3.3 Single Ion Monitoring (SIM) ............................................................ 110 5.3.4 Interfacing to API-MS ...................................................................... 110 5.3.5 Atmospheric Pressure Operation ...................................................... 110 5.3.6 Gas versus Liquid Phase Structure ................................................... 112 5.3.7 Mobility Range ................................................................................. 112 5.3.8 Miniaturization ................................................................................. 112 5.3.9 Limits to Resolution.......................................................................... 112 5.3.10 Linear versus Nonlinear Mobility Separation; Tandem DMA ......... 113
5.4 Experience with Tandem DMA-MS ............................................................. 113 5.5 Measurements with Protein Ions .................................................................. 114
5.5.1 Transitions......................................................................................... 116 5.5.2 Ionization Mechanism ...................................................................... 120 5.5.3 Larger Proteins ................................................................................. 120
5.6 Studies with Ionic Liquid Nanodrops ........................................................... 123 5.7 Electrosprayed Polymer Ions ........................................................................ 126
5.7.1 Polymers Soluble in Polar Solvents .................................................. 126 5.7.2 Water-Insoluble Polymers ................................................................. 131
5.8 Conclusions ................................................................................................... 131 Acknowledgments .................................................................................................. 133 References .............................................................................................................. 133
Numerous impressive studies on ion mobility spectrometry (IMS) in tandem with mass spectrometry (MS) have proven beyond any doubt the outstanding ability offered by this combination to (i) widen the range of species identifiable in complex biological mixtures, and (ii) provide structural information on complex ions.(1-5) The great potential impact of IMS-MS is so amply recognized that many laboratories that have followed its development are eager to incorporate IMS into their MS portfolios. This eagerness is particularly evident in the success of the only existing commercial IMS-MS system (Waters Synapt(6)), based on ion separation in a drift gas caused by a succession of travelling electrical waves (T waves). This solution, however, comes at some cost. First, the measured ion drift time is related to mobility in a complex and incompletely understood fashion, which limits the precision and reliability of the structural information obtained.(7) This is due to the fact that the travelling voltage wave pushing ions forward rises in each cycle as much as it falls, so its net effect is zero within the linear approximation. Only nonlinear effects survive on average, whose complex dependence on many details of the waveform and other circumstances is not easy to predict. Hence an extensive calibration effort is required, which is compounded by the lack of calibration standards of fixed mobility in the range of masses and mobilities typical of large biological ions. Second, the mobility resolution of the T-wave system, although extremely useful,(8) has been considerably smaller than that for the best pulsed IMS. This remains the case, although recent developments show T-wave resolving power of 45 for cross section.(9) Third, the capital investment required is high, as an entirely new tandem instrument needs to be acquired, rather than simply adding the mobility dimension to the many existing MS systems. Given the outstanding proven accomplishments of pulsed linear IMS-MS, its continuous development, and the importance of the structural information it unambiguously yields, it is surprising that it has not been successfully commercialized and widely adopted by clinical and research laboratories. This contrast between what the experts and the wider community can do is to a great measure attributable to the difficulty of incorporating the IMS component into the many well-developed existing MS systems.
