Flying in the Tube – Ion Mobility Mass Spectrometry (IM-MS) Technique

Imagine a technique that transitions from battlefields to our labs, capable of detecting chemical warfare agents and explosives. Nowadays, IM-MS stands out for its ability to unravel structural details that conventional mass spectrometry might miss. By analyzing the collision cross-section of ions, it reveals their three-dimensional shapes and sizes, offering deeper insights into molecular conformations. And, all of the processes occur while flying in the tube.

The Journey of the Ions
The journey begins with ionization, where the sample is transformed into charged particles. Techniques such as electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) are often employed to ensure the ions are ready for the next phase.

Figure: Schematic representation of the IM-MS working principle (Makinen et al.,2010).

Once ionized, these charged entities embark on their voyage through the ion mobility spectrometer. Here, they traverse a drift region filled with an inert gas under the influence of an electric field. This phase is where the magic of separation happens. The ions are sorted based on their size, shape, and charge—attributes that dictate their speed through the gas. Larger, bulkier ions lag behind, while smaller, more compact ions zip ahead.

Emerging from this initial separation, the ions are then funneled into the mass spectrometer. In this realm, they are separated once again, but this time by their mass-to-charge ratio (m/z). The mass spectrometer, whether it be a time-of-flight (TOF), quadrupole, or Orbitrap, captures and records these values, providing a detailed mass spectrum.

Leading-edge Applications and Emerging Fields
In the realm of proteins, IM-MS serves as a powerful tool for unraveling the intricate architectures of proteins, deciphering their dynamic behaviors, and elucidating complex protein interactions vital to biological processes. Meanwhile, in metabolomics, IM-MS facilitates in-depth analyses of metabolites within biological systems, shedding light on metabolic pathways and disease mechanisms. Its contributions to drug discovery are equally significant, as IM-MS aids in the comprehensive characterization of drug candidates, their binding interactions, and their metabolic fates. The application of IM-MS in biosimilar drug development is highly popular due to its ability to provide detailed comparisons between reference molecules and biosimilar candidates. By precisely analyzing the structural characteristics and compositions of these molecules, IM-MS facilitates the assessment of similarity and helps ensure the quality and efficacy of biosimilar drugs. Moreover, IM-MS plays a crucial role in environmental monitoring, enabling the detection and characterization of pollutants and complex mixtures in environmental samples.

Furthermore, by combining IM-MS with X-ray crystallography, researchers can gain insights into the dynamics of biomolecular systems both in solution and in the crystalline state. Overall, the integration of IM-MS with X-ray crystallography offers a powerful approach for studying biomolecular structure and function. By combining the strengths of both techniques, researchers can overcome limitations and obtain a more complete understanding of complex biological systems.

Reference:
Tatli, O., Oz, Y., Dingiloglu, B., Yalcinkaya, D., Basturk, E., Korkmaz, M., Akbulut, L., Hatipoglu, D., Kirmacoglu, C., Akgun, B., Turk, K., Pinar, O., Sariyar Akbulut, B., Atabay, Z., Tahir Turanli, E., Kazan, D., & Dinler Doganay, G. (2023). A two-step purification platform for efficient removal of Fab-related impurities: A case study for Ranibizumab. Heliyon, 9(11), e21001. https://doi.org/10.1016/j.heliyon.2023.e21001
Mäkinen, M. A., Anttalainen, O. A., & Sillanpää, M. E. (2010). Ion Mobility Spectrometry and its applications in detection of Chemical Warfare Agents. Analytical Chemistry, 82(23), 9594–9600.
Dodds, J. N., & Baker, E. S. (2019). Ion mobility spectrometry: fundamental concepts, instrumentation, applications, and the road ahead. Journal of the American Society for Mass Spectrometry, 30(11), 2185-2195.