SpringerLink
Log in

Integrating ion mobility into comprehensive multidimensional metabolomics workflows: critical considerations

  • Review Article
  • Published:
Metabolomics Aims and scope Submit manuscript

Abstract

Background

Ion mobility (IM) separation capabilities are now widely available to researchers through several commercial vendors and are now being adopted into many metabolomics workflows. The added peak capacity that ion mobility offers with minimal compromise to other analytical figures-of-merit has provided real benefits to sensitivity and structural selectivity and have allowed more specific metabolite annotations to be assigned in untargeted workflows. One of the greatest promises of contemporary IM-enabled instrumentation is the capability of operating multiple analytical dimensions inline with minimal sample volumes, which has the potential to address many grand challenges currently faced in the omics fields. However, comprehensive operation of multidimensional mass spectrometry comes with its own inherent challenges that, beyond operational complexity, may not be immediately obvious to practitioners of these techniques.

Aim of review

In this review, we outline the strengths and considerations for incorporating IM analysis in metabolomics workflows and provide a critical but forward-looking perspective on the contemporary challenges and prospects associated with interpreting IM data into chemical knowledge.

Key scientific concepts of review

We outline a strategy for unifying IM-derived collision cross section (CCS) measurements obtained from different IM techniques and discuss the emerging field of high resolution ion mobility (HRIM) that is poised to address many of the contemporary challenges associated with ion mobility metabolomics. Whereas the LC step limits the throughput of comprehensive LC-IM-MS, the higher peak capacity of HRIM can allow fast LC gradients or rapid sample cleanup via solid-phase extraction (SPE) to be utilized, significantly improving the sample throughput.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

AIF:

All Ions Fragmentation

CCS:

Collision Cross Section

cIM:

Cyclic Ion Mobility

DDA:

Data-Dependent Acquisition

DIA:

Data-Independent Acquisition

DTIMS:

Drift Tube Ion Mobility Spectrometry

FTMS:

Fourier Transform Mass Spectrometry

FWHM:

Full Width at Half Maximum

GC:

Gas Chromatography

HDMS:

High Definition Mass Spectrometry

HRdm:

High Resolution Demultiplexing

HRIM:

High Resolution Ion Mobility

IM:

Ion Mobility

LC:

Liquid Chromatography

m/z:

Mass-to-Charge Ratio

MRT:

Multi-Reflecting Time-of-Flight Mass Spectrometry

MS1:

Single Stage Mass Spectrometry

MS2:

Two-Stage Tandem Mass Spectrometry

MSn :

Multiple-Stage (n > 2) Tandem Mass Spectrometry

PASEF:

Parallel Accumulation–Serial Fragmentation

RT:

Retention Time

SLIM:

Structures for Lossless Ion Manipulations

SPE:

Solid-Phase Extraction

TIMS:

Trapped Ion Mobility Spectrometry

TOFMS:

Time-of-Flight Mass Spectrometry

TWIMS:

Traveling Wave Ion Mobility Spectrometry

TW-SLIM:

Traveling Wave Structures for Lossless Ion Manipulations

References

  • Ali, A., Davidson, S., Fraenkel, E., Gilmore, I., Hankemeier, T., Kirwan, J. A., Lane, A. N., Lanekoff, I., Larion, M., McCall, L. I., Murphy, M., Sweedler, J. V., & Zhu, C. (2022). Single cell metabolism: current and future trends. Metabolomics, 18, 77. https://doi.org/10.1007/s11306-022-01934-3.

    Article  CAS  Google Scholar 

  • Athersuch, T. (2016). Metabolome analyses in exposome studies: profiling methods for a vast chemical space. Archives of biochemistry and biophysics, 589, 177–186. https://doi.org/10.1016/j.abb.2015.10.007.

    Article  CAS  Google Scholar 

  • Breen, J., Hashemihedeshi, M., Amiri, R., Dorman, F. L., & Jobst, K. J. (2022). Unwrap** Wrap-around in gas (or Liquid) Chromatographic Cyclic Ion Mobility–Mass Spectrometry. Analytical Chemistry, 94, 11113–11117. https://doi.org/10.1021/acs.analchem.2c02351.

    Article  CAS  Google Scholar 

  • Causon, T. J., & Hann, S. (2020). Uncertainty estimations for collision cross section determination via uniform field drift tube-ion mobility-mass spectrometry. Journal of the American Society for Mass Spectrometry, 31, 2102–2110. https://doi.org/10.1021/jasms.0c00233.

    Article  CAS  Google Scholar 

  • Causon, T. J., Si-Hung, L., Newton, K., Kurulugama, R. T., Fjeldsted, J., & Hann, S. (2019). Fundamental study of ion trap** and multiplexing using drift tube-ion mobility time-of-flight mass spectrometry for non-targeted metabolomics. Analytical and bioanalytical chemistry, 1–10. https://doi.org/10.1007/s00216-019-02021-8.

  • Chaleckis, R., Meister, I., Zhang, P., & Wheelock, C. E. (2019). Challenges, progress and promises of metabolite annotation for LC–MS-based metabolomics. Current opinion in biotechnology, 55, 44–50. https://doi.org/10.1016/j.copbio.2018.07.010.

    Article  CAS  Google Scholar 

  • Collins, S. L., Koo, I., Peters, J. M., Smith, P. B., & Patterson, A. D. (2021). Current Challenges and recent developments in Mass Spectrometry–Based Metabolomics. Annual Review of Analytical Chemistry, 14, 467–487. https://doi.org/10.1146/annurev-anchem-091620-015205.

    Article  CAS  Google Scholar 

  • Davis, D. E. Jr., Leaptrot, K. L., Koomen, D. C., May, J. C., Cavalcanti, G. A., Padilha, M. C., Pereira, H. M., & McLean, J. A. (2021). Multidimensional separations of Intact Phase II Steroid Metabolites utilizing LC–Ion Mobility–HRMS. Analytical chemistry, 93, 10990–10998. https://doi.org/10.1021/acs.analchem.1c02163.

    Article  CAS  Google Scholar 

  • de Dias, S., Verbaere, A. L., Meudec, A., Deshaies, E., Saucier, S., Cheynier, C., V. and, & Sommerer, N. (2022). Improved analysis of Isomeric Polyphenol Dimers using the 4th dimension of trapped Ion mobility Spectrometry—Mass Spectrometry. Molecules, 27, 4176. https://doi.org/10.3390/molecules27134176.

    Article  CAS  Google Scholar 

  • Delafield, D. G., Lu, G., Kaminsky, C. J., & Li, L. (2022). High-end Ion Mobility Mass Spectrometry: A Current Review of Analytical Capacity in Omics Applications and Structural Investigations. TrAC Trends in Analytical Chemistry, 116761. https://doi.org/10.1016/j.trac.2022.116761.

  • Deng, L., Ibrahim, Y. M., Baker, E. S., Aly, N. A., Hamid, A. M., Zhang, X., Zheng, X., Garimella, S. V., Webb, I. K., & Prost, S. A. (2016). Ion mobility separations of isomers based upon long path length structures for lossless ion manipulations combined with mass spectrometry. ChemistrySelect, 1, 2396–2399. https://doi.org/10.1002/slct.201600460.

    Article  CAS  Google Scholar 

  • Dodds, J. N., May, J. C., & McLean, J. A. (2016). Investigation of the complete suite of the leucine and isoleucine isomers: toward prediction of Ion mobility separation capabilities. Analytical Chemistry, 89, 952–959. https://doi.org/10.1021/acs.analchem.6b04171.

    Article  CAS  Google Scholar 

  • Dodds, J. N., May, J. C., & McLean, J. A. (2017). Correlating resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of separation efficiency in Ion mobility spectrometry. Analytical Chemistry, 89, 12176–12184. https://doi.org/10.1021/acs.analchem.7b02827.

    Article  CAS  Google Scholar 

  • Drakopoulou, S. K., Damalas, D. E., Baessmann, C., & Thomaidis, N. S. (2021). Trapped Ion Mobility Incorporated in LC–HRMS Workflows as an Integral Analytical platform of high sensitivity: targeted and untargeted 4D-Metabolomics in Extra Virgin Olive Oil. Journal of Agricultural and Food Chemistry, 69, 15728–15737. https://doi.org/10.1021/acs.jafc.1c04789.

    Article  CAS  Google Scholar 

  • Feuerstein, M. L., Hernández-Mesa, M., Valadbeigi, Y., Le Bizec, B., Hann, S., Dervilly, G., & Causon, T. (2022). Critical evaluation of the role of external calibration strategies for IM-MS. Analytical and Bioanalytical Chemistry, 414, 7483–7493. https://doi.org/10.1007/s00216-022-04263-5.

    Article  CAS  Google Scholar 

  • Fiehn, O., Barupal, D. K., & Kind, T. (2011). Extending biochemical databases by metabolomic surveys. Journal of Biological Chemistry, 286, 23637–23643. https://doi.org/10.1074/jbc.R110.173617.

    Article  CAS  Google Scholar 

  • Gabelica, V., & Marklund, E. (2018). Fundamentals of ion mobility spectrometry. Current Opinion in Chemical Biology, 42, 51–59. https://doi.org/10.1016/j.cbpa.2017.10.022.

    Article  CAS  Google Scholar 

  • Gabelica, V., Shvartsburg, A. A., Afonso, C., Barran, P., Benesch, J. L., Bleiholder, C., Bowers, M. T., Bilbao, A., Bush, M. F., & Campbell, J. L. et al., (2019). Recommendations for reporting ion mobility Mass Spectrometry measurements. Mass spectrometry reviews, 38, 291–320. https://doi.org/10.1002/mas.21585.

    Article  CAS  Google Scholar 

  • German, J. B., Hammock, B. D., & Watkins, S. M. (2005). Metabolomics: building on a century of biochemistry to guide human health. Metabolomics, 1, 3–9. https://doi.org/10.1007/s11306-005-1102-8.

    Article  CAS  Google Scholar 

  • Giddings, J. C. (1984). Two-dimensional separations: concept and promise. Analytical Chemistry, 56, 1258A–1270. https://doi.org/10.1021/ac00276a003. A.

    Article  CAS  Google Scholar 

  • Giddings, J. C. (1987). Concepts and comparisons in multidimensional separation. Journal of High Resolution Chromatography, 10, 319–323. https://doi.org/10.1002/jhrc.1240100517.

    Article  CAS  Google Scholar 

  • Giles, K., Ujma, J., Wildgoose, J., Pringle, S., Richardson, K., Langridge, D., & Green, M. (2019). A cyclic Ion Mobility-Mass Spectrometry System. Analytical Chemistry, 91, 8564–8573. https://doi.org/10.1021/acs.analchem.9b01838.

    Article  CAS  Google Scholar 

  • Grabarics, M., Lettow, M., Kirk, A. T., von Helden, G., Causon, T. J., & Pagel, K. (2020). Plate-height model of ion mobility-mass spectrometry. The Analyst, 145, 6313–6333. https://doi.org/10.1039/D0AN00433B.

    Article  CAS  Google Scholar 

  • Grabarics, M., Lettow, M., Kirk, A. T., von Helden, G., Causon, T. J., & Pagel, K. (2021). Plate-height model of ion mobility-mass spectrometry: part 2—Peak-to-peak resolution and peak capacity. Journal of Separation Science, 44, 2798–2813. https://doi.org/10.1002/jssc.202100201.

    Article  CAS  Google Scholar 

  • Hernández-Mesa, M., D’atri, V., Barknowitz, G., Fanuel, M., Pezzatti, J., Dreolin, N., Ropartz, D., Monteau, F., Vigneau, E., & Rudaz, S. (2020). Interlaboratory and interplatform study of steroids collision cross section by traveling wave ion mobility spectrometry. Analytical chemistry, 92, 5013–5022. https://doi.org/10.1021/acs.analchem.9b05247.

    Article  CAS  Google Scholar 

  • Hinnenkamp, V., Klein, J., Meckelmann, S. W., Balsaa, P., Schmidt, T. C., & Schmitz, O. J. (2018). Comparison of CCS values determined by traveling wave ion mobility mass spectrometry and drift tube ion mobility mass spectrometry. Analytical chemistry, 90, 12042–12050. https://doi.org/10.1021/acs.analchem.8b02711.

    Article  CAS  Google Scholar 

  • HMDB The Human Metabolome Database, www.hmdb.ca (accessed October 4, 2022).

  • Ibrahim, Y. M., Hamid, A. M., Deng, L., Garimella, S. V. B., Webb, I. K., Baker, E. S., & Smith, R. D. (2017). New frontiers for mass spectrometry based upon structures for lossless ion manipulations. The Analyst, 142, 1010–1021. https://doi.org/10.1039/C7AN00031F.

    Article  CAS  Google Scholar 

  • Ieritano, C., Le Blanc, Y., Schneider, J., Bissonnette, B. B., Haack, J. R., A. and, & Hopkins, W. S. (2022). Protonation-Induced Chirality drives separation by Differential Ion mobility spectrometry. Angewandte Chemie International Edition, 61, e202116794. https://doi.org/10.1002/anie.202116794.

    Article  CAS  Google Scholar 

  • Kaufmann, A., Butcher, P., Maden, K., Walker, S., & Widmer, M. (2020). Does the ion mobility resolving power as provided by commercially available ion mobility quadrupole time-of-flight mass spectrometry instruments permit the unambiguous identification of small molecules in complex matrices? Analytica Chimica Acta, 1107, 113–126. https://doi.org/10.1016/j.aca.2020.02.032.

    Article  CAS  Google Scholar 

  • Kaufmann, A., Butcher, P., Maden, K., Widmer, M., Giles, K., & Uría, D. (2009). Are liquid chromatography/electrospray tandem quadrupole fragmentation ratios unequivocal confirmation criteria? Rapid Communications in Mass Spectrometry, 23, 985–998. https://doi.org/10.1002/rcm.3959.

    Article  CAS  Google Scholar 

  • Krug, S., Kastenmüller, G., Stückler, F., Rist, M. J., Skurk, T., Sailer, M., Raffler, J., Römisch-Margl, W., Adamski, J., & Prehn, C. (2012). The dynamic range of the human metabolome revealed by challenges. The FASEB Journal, 26, 2607–2619. https://doi.org/10.1096/fj.11-198093.

    Article  CAS  Google Scholar 

  • Lalli, P. M., Iglesias, B. A., Toma, H. E., de Sa, G. F., Daroda, R. J., Silva Filho, J. C., Szulejko, J. E., Araki, K., & Eberlin, M. N. (2012). Protomers: formation, separation and characterization via travelling wave ion mobility mass spectrometry. Journal of Mass Spectrometry, 47, 712–719. https://doi.org/10.1002/jms.2999.

    Article  CAS  Google Scholar 

  • Luo, M. D., Zhou, Z. W., & Zhu, Z. J. (2020). The application of ion mobility-mass spectrometry in untargeted metabolomics: from separation to identification. Journal of Analysis and Testing, 4, 163–174. https://doi.org/10.1007/s41664-020-00133-0.

    Article  Google Scholar 

  • Mahieu, N. G., & Patti, G. J. (2017). Systems-Level annotation of a Metabolomics Data Set reduces 25 000 features to fewer than 1000 unique metabolites. Analytical Chemistry, 89, 10397–10406. https://doi.org/10.1021/acs.analchem.7b02380.

    Article  CAS  Google Scholar 

  • May, J. C., Knochenmuss, R., Fjeldsted, J. C., & McLean, J. A. (2020). Resolution of Isomeric Mixtures in Ion mobility using a combined demultiplexing and peak deconvolution technique. Analytical Chemistry, 92, 9482–9492. https://doi.org/10.1021/acs.analchem.9b05718.

    Article  CAS  Google Scholar 

  • May, J. C., Leaptrot, K. L., Rose, B. S., Moser, K. L. W., Deng, L., Maxon, L., DeBord, D., & McLean, J. A. (2021). Resolving power and Collision Cross Section Measurement Accuracy of a Prototype High-Resolution Ion mobility platform incorporating structures for Lossless Ion Manipulation. Journal of the American Society for Mass Spectrometry, 32, 1126–1137. https://doi.org/10.1021/jasms.1c00056.

    Article  CAS  Google Scholar 

  • May, J. C., & McLean, J. A. (2015). Ion Mobility-Mass Spectrometry: Time-Dispersive Instrumentation. Analytical Chemistry, 87, 1422–1436. https://doi.org/10.1021/ac504720m.

    Article  CAS  Google Scholar 

  • May, J. C., & McLean, J. A. (2016). Advanced Multidimensional Separations in Mass Spectrometry: Navigating the Big Data Deluge. Annual Review of Analytical Chemistry9. https://doi.org/10.1146/annurev-anchem-071015-041734

  • May, J. C., Morris, C. B., & McLean, J. A. (2017). Ion mobility Collision Cross Section Compendium. Analytical Chemistry, 89, 1032–1044. https://doi.org/10.1021/acs.analchem.6b04905.

    Article  CAS  Google Scholar 

  • Michelmann, K., Silveira, J. A., Ridgeway, M. E., & Park, M. A. (2015). Fundamentals of Trapped Ion mobility spectrometry. Journal of The American Society for Mass Spectrometry, 26, 14–24. https://doi.org/10.1007/s13361-014-0999-4.

    Article  CAS  Google Scholar 

  • Moser, K. L. W., Van Aken, G., DeBord, D., Hatcher, N. G., Maxon, L., Sherman, M., Yao, L., & Ekroos, K. (2021). High-defined quantitative snapshots of the ganglioside lipidome using high resolution ion mobility SLIM assisted shotgun lipidomics. Analytica Chimica Acta, 1146, 77–87. https://doi.org/10.1016/j.aca.2020.12.022.

    Article  Google Scholar 

  • Nichols, C. M., Dodds, J. N., Rose, B. S., Picache, J. A., Morris, C. B., Codreanu, S. G., May, J. C., Sherrod, S. D., & McLean, J. A. (2018). Untargeted Molecular Discovery in primary metabolism: Collision Cross Section as a Molecular Descriptor in Ion Mobility-Mass Spectrometry. Analytical chemistry, 90, 14484–14492. https://doi.org/10.1021/acs.analchem.8b04322.

    Article  CAS  Google Scholar 

  • Ogata, K., & Ishihama, Y. (2020). Extending the separation space with trapped ion mobility spectrometry improves the accuracy of isobaric tag-based quantitation in proteomic LC/MS/MS. Analytical Chemistry, 92, 8037–8040. https://doi.org/10.1021/acs.analchem.0c01695.

    Article  CAS  Google Scholar 

  • Paglia, G., & Astarita, G. (2017). Metabolomics and lipidomics using traveling-wave ion mobility mass spectrometry. Nature protocols, 12, 797–813. https://doi.org/10.1038/nprot.2017.013.

    Article  CAS  Google Scholar 

  • Paglia, G., Smith, A. J., & Astarita, G. (2022). Ion mobility mass spectrometry in the omics era: Challenges and opportunities for metabolomics and lipidomics. Mass Spectrometry Reviews, 41, 722–765. https://doi.org/10.1002/mas.21686.

    Article  CAS  Google Scholar 

  • Picache, J. A., May, J. C., & McLean, J. A. (2020). Crowd-sourced chemistry: considerations for building a standardized database to improve omic analyses. ACS omega, 5, 980–985. https://doi.org/10.1021/acsomega.9b03708.

    Article  CAS  Google Scholar 

  • Picache, J. A., Rose, B. S., Balinski, A., Leaptrot, K. L., Sherrod, S. D., May, J. C., & McLean, J. A. (2019). Collision Cross Section Compendium to annotate and predict multi-omic compound identities. Chemical Science, 983–993. https://doi.org/10.1039/C8SC04396E.

  • Rappaport, S. M., Barupal, D. K., Wishart, D., Vineis, P., & Scalbert, A. (2014). The blood exposome and its role in discovering causes of disease. Environmental health perspectives, 122, 769–774. https://doi.org/10.1289/ehp.1308015.

    Article  CAS  Google Scholar 

  • Regueiro, J., Negreira, N., & Berntssen, M. H. (2016). Ion-mobility-derived collision cross section as an additional identification point for multiresidue screening of pesticides in fish feed. Analytical chemistry, 88, 11169–11177. https://doi.org/10.1021/acs.analchem.6b03381.

    Article  CAS  Google Scholar 

  • Ridgeway, M. E., Lubeck, M., Jordens, J., Mann, M., & Park, M. A. (2018). Trapped ion mobility spectrometry: a short review. International Journal of Mass Spectrometry, 425, 22–35. https://doi.org/10.1016/j.ijms.2018.01.006.

    Article  CAS  Google Scholar 

  • Rister, A. L., & Dodds, E. D. (2020). Steroid analysis by ion mobility spectrometry. Steroids, 153, 108531. https://doi.org/10.1016/j.steroids.2019.108531.

    Article  CAS  Google Scholar 

  • Rose, B. S., Leaptrot, K. L., Harris, R. A., Sherrod, S. D., May, J. C., & McLean, J. A. (2021). High confidence shotgun lipidomics using structurally selective ion mobility-mass spectrometry, Mass Spectrometry-Based Lipidomics, Springer. pp. 11–37. https://doi.org/10.1007/978-1-0716-1410-5_2

  • Rose, B. S., May, J. C., Picache, J. A., Codreanu, S. G., Sherrod, S. D., & McLean, J. A. (2022). Improving confidence in lipidomic annotations by incorporating empirical ion mobility regression analysis and chemical class prediction. Bioinformatics, 38, 2872–2879. https://doi.org/10.1093/bioinformatics/btac197.

    Article  CAS  Google Scholar 

  • Scalbert, A., Brennan, L., Manach, C., Andres-Lacueva, C., Dragsted, L. O., Draper, J., Rappaport, S. M., van der Hooft, J. J., & Wishart, D. S. (2014). The food metabolome: a window over dietary exposure. The American journal of clinical nutrition, 99, 1286–1308. https://doi.org/10.3945/ajcn.113.076133.

    Article  CAS  Google Scholar 

  • Schmitt-Kopplin, P., Hemmler, D., Moritz, F., Gougeon, R. D., Lucio, M., Meringer, M., Müller, C., Harir, M., & Hertkorn, N. (2019). Systems chemical analytics: introduction to the challenges of chemical complexity analysis. Faraday Discussions, 218, 9–28. https://doi.org/10.1039/C9FD00078J.

    Article  CAS  Google Scholar 

  • Shliaha, P. V., Bond, N. J., Gatto, L., & Lilley, K. S. (2013). Effects of traveling Wave Ion mobility separation on Data Independent Acquisition in Proteomics Studies. Journal of Proteome Research, 12, 2323–2339. https://doi.org/10.1021/pr300775k.

    Article  CAS  Google Scholar 

  • Silveira, J. A., Danielson, W., Ridgeway, M. E., & Park, M. A. (2016). Altering the mobility-time continuum: nonlinear scan functions for targeted high resolution trapped ion mobility-mass spectrometry. International Journal for Ion Mobility Spectrometry, 19, 87–94. https://doi.org/10.1007/s12127-016-0196-1.

    Article  CAS  Google Scholar 

  • Stow, S. M., Causon, T. J., Zheng, X., Kurulugama, R. T., Mairinger, T., May, J. C., Rennie, E. E., Baker, E. S., Smith, R. D., McLean, J. A., Hann, S., & Fjeldsted, J. C. (2017). An interlaboratory evaluation of Drift Tube Ion Mobility-Mass Spectrometry Collision Cross Section measurements. Analytical Chemistry, 89, 9048–9055. https://doi.org/10.1021/acs.analchem.7b01729.

    Article  CAS  Google Scholar 

  • Tejada-Casado, C., Hernández-Mesa, M., Monteau, F., Lara, F. J., del Olmo-Iruela, M., García-Campaña, A. M., Le Bizec, B., & Dervilly-Pinel, G. (2018). Collision cross section (CCS) as a complementary parameter to characterize human and veterinary drugs. Analytica chimica acta, 1043, 52–63. https://doi.org/10.1016/j.aca.2018.09.065.

    Article  CAS  Google Scholar 

  • Uppal, K., Walker, D. I., Liu, K., Li, S., Go, Y. M., & Jones, D. P. (2016). Computational metabolomics: a framework for the million metabolome. Chemical research in toxicology, 29, 1956–1975. https://doi.org/10.1021/acs.chemrestox.6b00179.

    Article  CAS  Google Scholar 

  • Vasilopoulou, C. G., Sulek, K., Brunner, A. D., Meitei, N. S., Schweiger-Hufnagel, U., Meyer, S. W., Barsch, A., Mann, M., & Meier, F. (2020). Trapped ion mobility spectrometry and PASEF enable in-depth lipidomics from minimal sample amounts. Nature communications, 11, 1–11. https://doi.org/10.1038/s41467-019-14044-x.

    Article  CAS  Google Scholar 

  • Wasito, H., Causon, T., & Hann, S. (2022). Alternating in-source fragmentation with single-stage high-resolution mass spectrometry with high annotation confidence in non-targeted metabolomics. Talanta, 236, 122828. https://doi.org/10.1016/j.talanta.2021.122828.

    Article  CAS  Google Scholar 

  • Wu, Q., Wang, J. Y., Han, D. Q., & Yao, Z. P. (2020). Recent advances in differentiation of isomers by ion mobility mass spectrometry. TrAC Trends in Analytical Chemistry, 124, 115801. https://doi.org/10.1016/j.trac.2019.115801.

    Article  CAS  Google Scholar 

  • **a, J., **ao, W., Lin, X., Zhou, Y., Qiu, P., Si, H., Wu, X., Niu, S., Luo, Z., & Yang, X. (2022). Ion mobility-derived collision cross-sections add Extra Capability in distinguishing Isomers and Compounds with similar Retention Times: the case of Aphidicolanes. Marine Drugs, 20, 541. https://doi.org/10.3390/md20090541.

    Article  CAS  Google Scholar 

  • Xu, Z., Li, J., Chen, A., Ma, X., & Yang, S. (2018). A new retrospective, multi-evidence veterinary drug screening method using drift tube ion mobility mass spectrometry. Rapid Communications in Mass Spectrometry, 32, 1141–1148. https://doi.org/10.1002/rcm.8154.

    Article  CAS  Google Scholar 

  • Zenobi, R. (2013). Single-cell metabolomics: analytical and biological perspectives. Science, 342, 1243259. https://doi.org/10.1126/science.1243259.

    Article  CAS  Google Scholar 

  • Zhang, X., Romm, M., Zheng, X., Zink, E. M., Kim, Y. M., Burnum-Johnson, K. E., Orton, D. J., Apffel, A., Ibrahim, Y. M., Monroe, M. E., Moore, R. J., Smith, J. N., Ma, J., Renslow, R. S., Thomas, D. G., Blackwell, A. E., Swinford, G., Sausen, J., Kurulugama, R. T., Eno, N., Darland, E., Stafford, G., Fjeldsted, J., Metz, T. O., Teeguarden, J. G., Smith, R. D., & Baker, E. S. (2016). SPE-IMS-MS: an automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids. Clinical Mass Spectrometry, 2, 1–10. https://doi.org/10.1016/j.clinms.2016.11.002.

    Article  Google Scholar 

  • Zheng, X., Aly, N. A., Zhou, Y., Dupuis, K. T., Bilbao, A., Paurus, V. L., Orton, D. J., Wilson, R., Payne, S. H., & Smith, R. D. (2017). A structural examination and collision cross section database for over 500 metabolites and xenobiotics using drift tube ion mobility spectrometry. Chemical Science, 8, 7724–7736. https://doi.org/10.1039/C7SC03464D.

    Article  CAS  Google Scholar 

  • Valentina, Calabrese Isabelle, Schmitz-Afonso Candice, Prevost Carlos, Afonso Abdelhakim, Elomri (2022) Molecular networking and collision cross section prediction for structural isomer and unknown compound identification in plant metabolomics: a case study applied to Zhanthoxylum heitzii extracts. Analytical and Bioanalytical Chemistry 414(14) 4103-4118 10.1007/s00216-022-04059-7

    Article  CAS  Google Scholar 

  • Zhiwei, Zhou Mingdu, Luo **, Chen Yandong, Yin **n, **ong Ruohong, Wang Zheng-Jiang, Zhu (2020) Ion mobility collision cross-section atlas for known and unknown metabolite annotation in untargeted metabolomics. Nature Communications 11(1) 4334 10.1038/s41467-020-18171-8

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part using the resources of the Center for Innovative Technology (CIT) at Vanderbilt University. Financial support for aspects of this work was provided by the U.S. Environmental Protection Agency (EPA) under grant No. R839504. This work has not been formally reviewed by the EPA and EPA does not endorse any products or commercial services mentioned in this document. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the EPA or the U.S. Government.

Author information

Authors and Affiliations

  1. Center for Innovative Technology, Department of Chemistry, Vanderbilt University, Nashville, TN, USA

    Jody C. May & John A. McLean

Authors
  1. Jody C. May
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John A. McLean
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally to this work.

Corresponding author

Correspondence to John A. McLean.

Ethics declarations

Statements and declarations

The authors acknowledge collaborative agreements with Waters Corporation, Agilent Technologies, and MOBILion Systems, which are manufacturers of ion mobility instrumentation. JAM is a member of the Scientific Advisory Board for MOBILion Systems. The authors certify that their contributions are scientifically objective and are not influenced by these collaborative agreements or SAB participation.

Competing interests

The authors acknowledge collaborative agreements with Waters Corporation, Agilent Technologies, and MOBILion Systems, which are manufacturers of ion mobility instrumentation. JAM is a member of the Scientific Advisory Board for MOBILion Systems. The authors certify that their contributions are scientifically objective and are not influenced by these collaborative agreements or SAB participation.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

May, J.C., McLean, J.A. Integrating ion mobility into comprehensive multidimensional metabolomics workflows: critical considerations. Metabolomics 18, 104 (2022). https://doi.org/10.1007/s11306-022-01961-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11306-022-01961-0

Keywords

Search

Navigation