IM is a technique that separates gas-phase protein structures based on their orientationally averaged collision cross-section (CCS) and has emerged as a useful technique for the characterization of biological macromolecules². To obtain CCS values, gas-phase protein ions are injected into a drift cell that is filled with an inert gas, e.g. nitrogen or helium.  The ions drift from the entrance to the exit of an ion guide under the influence of a weak electric field. The electric potential forms a gradient that propels the ions towards the exit of the guide. As the ions traverse the guide, they undergo hundreds of thousands of low-energy collisions with the neutral buffer gas. During IM separation, large ions collide more frequently with the buffer gas than those that are smaller, resulting in differences in migration time, or drift time, to the mass spectrometer detector. This drift time can then be converted to a CCS value by using the Mason-Schamp equation, and as such IM separates protein ions in a way that is highly correlated to ion size, shape, and charge (Figure 1)^3,4.

When coupled to MS, drift times from IM-MS experiments can be correlated with ion compositions that reveal the influences on protein structure and conformation as a result of sequence changes^5,6, small molecule conjugation⁷, and post-translational modification on proteins as large as antibody structures^8,9.

We envision that IM-MS would improve the analysis for works of art in two ways. First, it would allow proteinaceous materials higher order structures to be characterized without the need for material intensive separation techniques typically used to “clean” the sample prior to MS analysis. Secondly, it would simultaneously provide separation of small molecules or dyes which often contain structural isomers that are difficult to separate by traditional MS techniques alone.