The Road to HPLC2018 Part III: Catching the Next Wave in IMS
Technological advances are putting IMS at the forefront of separation science – so it’s a guaranteed hot topic for HPLC2018.
Richard Smith |
Ion mobility spectrometry (IMS) originated more than a century ago and, to date, has been mainly used for chemical weapon agent detection and airport passenger screening. Though the field has been developing steadily over the years, IMS is only now transitioning to the top tier of analytical separation methods.
In IMS, ions collide with a buffer gas and separate due to their different shape-dependent velocities in an electric field. In high vacuum, without collisions with gas molecules, the result would be a separation based upon the ion’s mass and charge – in other words, mass spectrometry (MS). On the other hand, if the IMS separation were to occur in a liquid (and in the presence of oppositely charged ions) it would be electrophoresis. Since ions attain much higher velocities in gases than in liquids, IMS separations occur much faster than liquid-based separations, with some forms achieving useful separations in milliseconds for compounds that might take minutes to an hour to effectively separate by HPLC.
IMS has become an increasingly popular front-end adjunct to MS. In fact, nearly every major MS vendor now offers an IMS-MS system in its portfolio. As well as faster analysis speeds, the two-dimensional platform provides significantly increased overall peak capacities over MS alone – and even greater increases when combined with more conventional separations; for example, LC-IMS-MS.
Currently, limited IMS path lengths constrain its resolving power (Rp) or peak capacity when compared to MS, or even LC. Achievable Rp increases with path length for both IMS and MS, with maximum path lengths limited by the practical maximum electric field and voltage (for example, in drift-tube IMS), cost of building longer path devices, reasonable platform size, and the increased ion losses incurred with longer ion drift paths. At very low gas pressures, the effects of ion–gas collisions are a minor perturbation to MS, generally causing a broadening and subtle shifting of peaks, which results in some loss of both Rp and mass measurement accuracy. The Rp feasible with IMS is constrained by diffusion in the gas to much smaller values (no more than a few hundred at present and often much less depending on the form of IMS).
But new opportunities are opening up due to the combination of two key advances in technology. One of these developments occurred more than a decade ago – the use of traveling waves (TW) in the Waters Synapt IMS-MS platform. TW IMS combines time and space variation of electric fields to induce the movement of ions along the path of the waves (a 25 cm path in the Synapt 2), with separation based upon the mobility-dependent ability of ions to “keep up” with the TW.
The second, more recent, development was Structures for Lossless Ion Manipulations (SLIM), from my group at PNNL. SLIM are literally constructed from electric fields, using arrays of electrodes patterned on two closely spaced planar surfaces to generate the fields. SLIM represents a dramatic departure in how ions in gases are focused and manipulated, allowing ions to be efficiently transmitted through turns, switched between paths, and stored losslessly over long time periods. The use of TW in SLIM enables the design of long compact serpentine IMS paths. A 13 m SLIM IMS provided over five-times greater Rp than the best drift tube or TW IMS commercially available, allowing baseline separation of structurally similar and previously challenging isomers, for example.
Though these early results are exciting, they are only the start of IMS separation enhancements to come. SLIM multi-level 3D implementations will allow much longer path separations (perhaps kilometers!) and provide the basis for compact IMS designs. SLIM ion switches open the door for multi-pass separations over potentially unlimited path lengths. SLIM also allows the temporal and spatial compression of peaks and even the “squeezing” of whole IMS separations without loss of resolution, as well as the injection and effective use of much larger ion populations for increased S/N.
SLIM IMS is riding a wave to exciting new separation capabilities, and I look forward to sharing more about the possibilities in my plenary talk at HPLC2018!
HPLC 2018 takes place on 29 July to 2 August in Washington, DC.
Richard D. Smith is Battelle Fellow and Chief Scientist, Biological Sciences Division, Pacific Northwest National Laboratory (PNNL), Richland, Washington, USA.
