DOE OSTI2012
Q1. What are your main research activities in ion mobility mass spectrometry (past or present)? My early efforts focused on the structural characterization of atomic (carbon and semiconductor) clusters. After the production of bulk fullerenes, many hoped that other nanoclusters discovered in the gas phase could also coalesce into new materials. As these studies required accurate and robust mobility calculations for any ion geometry, I strived to build the needed theory and implement it in the Mobcal software widely employed today. Since 2004, I have been developing methods and novel applications of differential IMS (FAIMS) at PNNL. The principal achievement has been raising the resolving power by over tenfold (up to ~400 for multiply-charged peptides) using elevated fields, helium and hydrogen-rich buffers, and extended filtering times. This performance broadly allows previously unthinkable separations of very similar species, for example sequence inversions and post-translational modification localization isomers of peptides (including “middle-down” peptides such as histone tails), lipid regioisomers, and even isotopomers. Another major direction is investigating the dipole alignment of larger proteins, which creates an exceptionally strong FAIMS effect that is a potential tool for structural biology. Q2: What have been the most significant instrumentation or applications developments in the history of ion mobility - mass spectrometry? In 1995 when I started graduate research at Northwestern, only two groups worldwide worked with IMS/MS and “the literature” meant papers by Bowers (UCSB). Well-wishers counseled me to “learn something useful like HPLC, as IMS would never have real utility”. This booklet showcases the scale of change since. First, the practical IMS/ToF platforms for complex biological analyses demonstrated by Clemmer have turned IMS/MS from an esoteric physical chemistry technique into a powerful analytical tool. By commercializing the IMS/ToF technology in Synapt instruments, Waters has greatly increased its impact via expanded number and diversity of applications. Concurrently, Guevremont at Canadian NRC has perfected FAIMS coupled to MS, deployed it for real-world bio and environmental analyses, and widely distributed it in the Ionalytics Selectra system (subsequently installed on Thermo MS platforms). The latest breakthrough is ultra-FAIMS by Owlstone, where extreme fields allow numerous qualitatively new separations and operational modes that we just begin to explore. Q3: Where do you see ion mobility - mass spectrometry making the most impact in the next 5 years? Any predictions for where the field will go? Sciences dealing with perturbations in media (such as optics or acoustics) at some point shift from the linear to nonlinear paradigm, where propagation depends on the magnitude of perturbation or its driving force. While the linear part remains industrially important (e.g., eyewear and architectural glass for optics), frontline research moves to nonlinear phenomena. IMS is undergoing that transition now with the rise of FAIMS, which should continue as the fundamental understanding improves, new modalities and applications emerge, and more instrumentation is introduced by vendors. Modifying and augmenting FAIMS separations through vapor dopants that render ion mobilities less linear is becoming routine. I expect this area to advance, extending to more specific interactions and to complexation with solution additives. Another route to higher separation power is integrating FAIMS with conventional IMS; proliferation of both technologies would make such 2-D platforms common. Along with mass spectrometry and conventional IMS, FAIMS will address increasingly large macromolecules, including proteins and their complexes.
Shvartsburg, Alexandre A.↗