An insight into IMS-MS imaging

Author: Emmanuelle Claude 

Chemical imaging gives us the ability to provide direct insight into the localization of molecules within a sample. This is vital for exploring the distribution and complex interactions of biomolecules in living organisms to arrive at a better understanding of the principles of life. Mass Spectrometry (MS) imaging technology has emerged as a powerful answer to the need for robust chemical imaging techniques, bypassing the need for chemical labels. By mapping both the abundance and distribution of molecules in materials, it has quickly developed into a key pillar of imaging studies in a wide array of fields, including medicine, toxicology, plant biology, and ‘omics’ studies. Coupling with ion mobility spectrometry (IMS) has been shown to greatly enhance the discriminating power of MS imaging, and paves the way for more confident identifications in research. [1,2]

IMS-MS for Chemical Imaging 

IMS rapidly separates molecules in the gas phase based on their size, shape and charge. Essentially, IMS provides the capability to rapidly distinguish between structural isomers, isobaric species and remove chemical noise. These advanced separation capabilities allow IMS to quickly clean up spectra and simplify data analysis. [1] It also facilitates identification of multiply-charged species generated in the experiment, which can add a wealth of information. Furthermore, separation of parent molecules based on their drift times in IMS helps to clarify fragmentation patterns.

MS imaging, meanwhile, is commonly undertaken with either matrix assisted laser desorption ionization (MALDI) or desorption electrospray ionization (DESI) technology to desorb and ionize sample molecules directly from the surface of thin sections of tissue. MS then distinguishes the ions based on their mass-to-charge ratio, generating an array of mass spectra linked to co-ordinates on the surface, thus creating chemical maps of the sample. Together, MALDI and DESI cover many research needs and molecular classes. 

MALDI-MS is able to accurately study both large and small molecules, although some sample preparation is required. DESI-MS, on the other hand, requires significantly less sample preparation and yields rich data without accruing sample damage, though it cannot match the spatial resolution of MALDI. Recently, it has been shown that with additional preparation steps, DESI can generate significant quantities of multiply-charged ions allowing intact proteins to be imaged within the sample. [3,4] Due to the complexity of the mass spectrum obtained directly from a tissue section, these multiply-charged protein species would not be seen without the additional separation offered by ion mobility.

Furthermore, as mass spectra acquired by direct sample desorption are inherently complex, it is extremely difficult to pair MS imaging with chromatography. IMS serves to bridge the gap, offering an additional dimension of separation without modification to the desorption/ionization step, and on the same timescale as the imaging experiment. IMS-MS in imaging studies combines the benefits of both IMS and MS imaging to produce critical information about the spatial distribution of molecules in a sample, in addition to their mass, shape, and charge. This paves the way for advanced imaging studies.  [2] 

Contribution to Biomedical Research

The addition of IMS to MS imaging can greatly increase confidence in identification by reducing the background noise. With technological advances allowing direct detection of proteins in tissue without the need to attach labels, IMS-MS offers clear advantages for protein imaging studies. For example, it was found to add significant power to the analysis of proteins in tissue following tryptic digestion. [5]

IMS-MS also has a number of exciting applications across the biomedical field. [2] Its ability to effectively identify chemicals in complex samples makes it an incredibly valuable tool for use in pharmaceutical research. For example, it was used to map the distribution of anti-cancer drug vinblastine in mouse tissue, prior and post-dose. [6] IMS-MS also enables the in situ identification of biomarkers, including those related to pancreatic cancer, and can aid the classification of tumors to help medical professionals comprehensively characterize cancers. [2,7] With the SYNAPT XS, the resolution offered by IMS-MS will become even higher, further advancing biomedical research. [8]

Imaging the Metabolome and Lipidome

IMS-MS can identify metabolites in biological tissue, helping researchers to confirm with confidence alterations to molecules arising from metabolic processes. For example, IMS-MS analyzed the effect of cocaine on neuronal rat metabolomes, enhancing our understanding of the metabolic changes caused by drug abuse. [9]

Furthermore, as lipids ionize easily and often have different isobaric forms, IMS-MS is tremendously useful for elucidating lipid structures. This is significant for the pharmaceutical industry as lipids can be associated with different diseases, and therapeutic compounds can be stored in the body’s adipose tissue. IMS-MS has been successfully used to identify phospholipids in rat brains and to identify noncovalent complexes formed by phospholipids, laying the groundwork for future research. [1, 10-12]

Conclusion and Future Outlook

IMS-MS has an extensive range of exciting chemical imaging applications. The key advantages include high-throughput separation of isomers and isobaric species – which is particularly important as chromatography is unfeasible for MS imaging studies – and ionization techniques that allow for in situ imaging. The latter is especially useful for protein studies, as it removes the need for protein labelling and speeds up identification. IMS-MS applications in biomedical research include lipidome and metabolome profiling, biomarker detection and even cancer diagnosis. With the latest technological advances, the future of IMS-MS imaging looks bright: powerful separation techniques and improved resolution are allowing researchers to see more than ever before.  

 Further reading: 

  1. Current Opinion in Chemical Biology, Volume 42, 2018, Pages 147-159,
  2. Anal Bioanal Chem. 2011 Mar; 399(8): 2623–2634.  doi: 10.1007/s00216-010-4644-1
  3. J. Am. Soc. Mass Spectrom. (2018) 29, 2456.2466 doi: 10.1007/s13361-018-2049-0 DESI Synapt work from Wilmlsow 
  4. Anal Chem. 2018 Jul 3;90(13):7785-7789. doi:10.1021/acs.analchem.8b00967 (ultra) FAIMS work on LTQ-Orbitrap and DESI 
  5. Stauber, J., MacAleese, L., Franck, J. et al. J Am Soc Mass Spectrom (2010) 21: 338.
  6. Anal. Chem.200880228628-8634 Publication Date: October 11, 2008.
  7. Proteome Res.20098104876-4884.
  9. Kaplan, K.A., Chiu, V.M., Lukus, P.A. et al. Anal Bioanal Chem (2013) 405: 1959.
  10. Armenta, S. & Blanco, M. Anal Bioanal Chem (2011) 401: 1935.
  11. Anal. Chem. 20158721137-1144.
  12. Jackson, S.N., Wang, HY.J., Woods, A.S. et al. J Am Soc Mass Spectrom (2005) 16: 133.