Department of Energy Scientists Use Mass Spectrometry to Identify Unknown Compounds

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Scientists from the Department of Energy’s Pacific Northwest National Laboratory (PNNL) and GAA Custom Engineering are using high-resolution ion mobility spectrometry-mass spectrometry (HR-IMS-MS) to characterize complex biological mixtures. The work could be a first step in helping to identify unknown compounds, according to the study, which was published in Analytical Chemistry (1).

The research was done as part of the m/q Initiative, which aims to identify unknown chemical compounds that could be used to cure diseases or identify chemical or biological threats, for example.

The researchers, led by PNNL chemist Adam Hollerbach, used a dual-gated ion injection to couple an 11-m pathlength structures for lossless ion manipulations (SLIM) module to an orbital trap MS platform (4). SLIM is a type of ion mobility spectrometer that measures the size and electric charge on an ion. Winding paths within the device create a 42-foot-long track for ions to race around, avoiding known molecules so scientists can record how long it takes for them to complete the course.

“Perhaps the main attraction of this system is that it provides high-resolution ion mobility measurements and high-resolution mass spectrometry measurements at the same time on the same sample,” Hollerbach told LCGC in an email. “This means you’ll get a single data file with all the measurements contained in it, which makes interpreting the data much faster, and thus the overall analysis is more efficient.” One ion gate was placed before the SLIM module while another was put after it, allowing the platform to perform a 11-m SLIM separation, Orbitrap mass analysis using the highest selectable mass resolution setting (up to 140 k), and high-energy collision-induced dissociation (HCD) in ∼25 min over an m/z range of ∼1500 amu. The technique is applicable to ions with positive or negative charges, rendering it easier to control and detect them with mass spectrometry.

The SLIM-orbitral trap MS analysis with fragmentation was performed on mixtures consisting of standard peptides and two reverse peptides (SDGRG1+, GRGDS1+, and RpCCS = 305). The system was also used to analyze a complex lipid mixture and showcase SLIM separations on isobaric lipids.

“While we’ve demonstrated these measurements with biological samples, at its core the MS system we used is an ion mobility-mass spectrometer,” Hollerbach said. “These systems can analyze almost any ion that you put into them, and we aim to expand our capabilities to other research areas that have lots of difficult samples to analyze.”

Scientists from the initiative are using data from Hollerbach’s work to predict an ion’s structure. Some PNNL researchers are working with fentanyl, for example, to better understand the forms of its compound and how it would behave inside a mass spectrometer, according to a press release.

"To be able to predict an unknown compound’s structure, you need to measure as many properties of the compound with as much detail as possible,” Hollerbach said. “This goal certainly can’t be achieved in a single shot; we have several projects underway that contribute different pieces to the puzzle.”


For more information on this study and the m/q Initiative, please refer to the sources listed in the References and Further Reading section (1–5).

References and Further Reading

(1) Hollerbach, A. L.; Ibrahim, Y. M.; Meras, V.; Norheim, R. V.; Huntley, A. P.; Anderson, G. A.; Metz, T. O.; Ewing, R. G.; Smith, R. D. A Dual-Gated Structures for Lossless Ion Manipulations-Ion Mobility Orbitrap Mass Spectrometry Platform for Combined Ultra-High-Resolution Molecular Analysis. Anal. Chem. 2023, 95 (25), 9531-9538. DOI: 10.1021/acs.analchem.3c00881

(2) World Health Organization. Guidance on chemicals and health.WHO 2023. (accessed 2023-07-28)

(3) EurekAlert! Chemists are on the hunt for the other 99 percent. American Association for the Advancement of Science (AAAS) 2023. (accessed 2023-07-28)

(4) Pacific Northwest National Laboratory. Thomas O. Metz. Department of Energy 2023. (accessed 2023-07-28)

(5) Pacific Northwest National Laboratory. Adam Hollerbach. Department of Energy 2023. (accessed 2023-07-28)

About the Author

Aaron Acevedo is the Assistant Editor for LCGC and Spectroscopy. Direct correspondence to: