Mass Spectrometry
A Multi-Function Cyclic Ion Mobility - Mass Spectrometry System Kevin Giles, Waters Corporation
Interest in ion mobility (IM) separation coupled with mass spectrometry (MS) has grown considerably over the past couple of decades, fi nding utility in a broad range of application areas ranging from the study of small molecules to large protein complexes where either more peak capacity is required or determination of collision cross-section (CCS) values for analyte ion structural elucidation or confi rmation is sought. Key to the resurgent development of IM-MS as an analytical technology has been the pioneering work of a number of academic research groups including Bowers (University of California Santa Barbera), Jarrold (Indiana University), Clemmer (Indiana University) and Hill (Washington State University) whose focus has been towards its application to the study of biological molecules. Another factor fuelling the growth in adoption of IM-MS has been the concomitant development and availability of instruments which provided both improved mobility resolution and higher transmission effi ciency - the latter being pivotal to the analysis of biological samples at analytically relevant levels. The fi rst high-performance commercial IM-MS system was the SYNAPTTM HDMSTM (Waters Corporation) quadrupole (Q)-IM-time-of-fl ight (ToF) instrument which was launched in 2006. This system provided high transmission effi ciency in IM operation through use of ion accumulation and mobility separation in a radially-confi ning ion guide (minimising diffusive losses). This instrument also featured the fi rst travelling wave (TW)-based mobility separator where, rather than the uniform, time invariant, electric fi eld used in classical drift tubes, a repeating series of voltage pulses are continually passed through the device to provide mobility separation.
Over the ensuing years a number of iterations of the SYNAPT instrument, as well as introductions of commercial IM-MS instruments from other MS vendors, but the Q-IM-ToF arrangement remains unique to Waters and provides users with experimental fl exibility to perform IM separation on either precursor and/or fragment ions. The desire to provide analysts and researchers with improved instrumentation, both in terms of raw performance and functionality, has rapidly driven the development of the technology. In 2019 Waters introduced the revolutionary SELECT SERIESTM CyclicTM IMS providing a step change in the performance of commercially available instrumentation with both extremely high mobility resolution and the capability to do multiple stages of IM separation [1, 2].
A schematic of the Cyclic IMS instrument is shown in Figure 1(a). The instrument utilises the Q-IM-ToF geometry and, signifi cantly, as the name suggests, the TW- IMS separator is cyclic rather than linear. The cyclic geometry enables ion mobility separation to occur over one or multiple passes around the device which provides ‘dial- up’ mobility resolving power (R) in a compact form.
(a)
switch function to facilitate the injection of ions into the device and ejection of ions from the device following mobility separation. The array can also be used to eject segments of the mobility separated ions to a pre-array store or a post-array store whilst the rest of the ions are removed, the stored ions are then re-admitted into the IM region for further separation. The stored ions can be activated, if required, on re-entry to the IM region to allow investigations of energy on the conformation of the ions or of the mobilities of fragment ions. The process of separation: isolation: activation: separation can be repeated many times, providing an IMSn function in analogy with the MSn capability of ion trap mass spectrometers.
The ‘dial-up’ resolving power capability of the cyclic IMS device is illustrated in Figure 2 for the separation of two sodiated isomeric trisaccharides; Melezitose and Raffi nose at m/z 527.2.
(b) (c)
Figure 1. (a) Instrument schematic showing the Q-IM-ToF geometry. (b) Graphic showing the orthogonal arrangement of the Cyclic IMS and neighbouring ion optics. (c) Multi-function region (Reproduced with permission from ref [1]. Copyright 2019, Ujma et al.)
Figure 1. (a) Instrument schematic showing the Q-IM-ToF geometry. (b) Graphic showing the orthogonal arrangement of the Cyclic IMS and neighbouring ion optics. (c) Multi-function region (Reproduced with permission from ref [1]. Copyright 2019, Ujma et al.)
Arrival Time (arb units)
The cyclic IMS device has a 98 cm separation pathlength and is arranged orthogonally to the main ion optical axis of the mass spectrometer. It is operated at a pressure of ~2
mBar of N2 and with travelling waves of up to 50 V amplitude and velocities generally in the 300 - 1000 m/s range. The enabling aspect of the design is the multifunction ion entry/separation/exit region of the IM device, consisting of an electrode array (Figure 1(c)). This region appears essentially identical to the main separation channel of the mobility device when separation is occurring (enabling multi-pass operation) but can
The cyclic IMS device has a 98 cm separation pathlength and is arranged orthogonally to the main ion optical axis of the mass spectrometer. It is operated at a pressure of ~2 mBar of N2 and with travelling waves of up to 50 V amplitude and velocities generally in the 300 - 1000 m/s range. The enabling aspect of the design is the multifunction ion entry/separation/exit region of the IM device, consisting of an electrode array (Figure 1(c)). This region appears essentially identical to the main separation channel of the mobility device when separation is occurring (enabling multi-pass operation) but can switch function to facilitate the injection of ions into the device and ejection of ions from the device following mobility separation. The array can also be used to eject segments of the mobility separated ions to a pre-array store or a post-array store whilst the rest of the ions are removed, the stored ions are then re-admitted into the IM region for further separation. The stored ions can be activated, if required, on re-entry to the IM region to allow investigations of energy on the conformation of the ions or of the mobilities of fragment ions. The process of separation: isolation: activation: separation can be repeated many times, providing an IMSn function in analogy with the MSn capability of ion trap mass spectrometers. The ‘dial-up’ resolving power capability of the cyclic IMS device is illustrated in Figure 2 for the separation of two sodiated isomeric trisaccharides; Melezitose and Raffinose at m/z 527.2.
Figure 2. Cyclic IMS separation of two isomeric trisaccharides, Melezitose and Raffi nose as a function of the number of passes (where R is the measured resolving power). The two species are separable because of their differing CCS (Ω) values.
Figure 2. Cyclic IMS separation of two isomeric trisaccharides, Melezitose Raffinose as a function of the number of passes (where R is the measured power). The two species are separable because of their differing CCS (Ω)
It can be seen that R increases with increasing number of passes (n) around the cyclic IMS, and, as expected from theory, the resolution scales as √n. To date, the highest resolving power achieved on the cyclic IMS for singly charged ions is ~750 which
It can be seen that R increases with increasing number of passes (n) aroun cyclic IMS, and, as expected from theory, the resolution scales as Ön. To d highest resolving power achieved on the cyclic IMS for singly charged ions which required 100 passes (98 m separation length) around the device [2].
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