Imaging Secondary Ion Mass Spectrometry (SIMS)

Secondary ion mass spectrometry (SIMS) fires a focused beam of (primary) ions at the sample that sputter atoms and molecules from a sample surface. Some of the ejected species become charged and it is these (secondary) ions that are detected by the mass spectrometer.

The detection of different chemicals can depend greatly on the type of primary ions that re fired at the sample surface. For many years SIMS analysis was limited to the detection of atoms, very small molecules, or fragments of molecules. We utilize new gas cluster ion beams where each primary ion is a cluster of several thousand gas atoms/molecules for example (CO2)6000.

We have shown that these beams dramatically increase the detection of intact molecules from biological samples and continue to improve on this approach through the use of new types of ion beams such as water cluster ions.

Mass spectrometry imaging offers a route to molecular pathology. Unlike other histological methods imaging MS does not require staining or labelling of the tissue. Thin slices (typically 5-20 µm thick) are analysed in order to elucidate changes in chemistry as a result of disease or injury for example in heart infarction, cancer or neurodegenerative disease. While many chemical types are accessible, we focus on the development of in situ lipidomic analysis where more conventional staining and optical imaging is not possible. We collaborate with clinicians and life science researchers in studies of both human and animal model samples.

Photo: SIMS imaging showing the increase in polyunsaturated fatty acid containing PI-lipids when inflammatory cells are present around a breast cancer tumour. The tumour mass is in the bottom left corner of the 1 x 1 mm2 image and inflammatory cells in the upper right.

The focused ion beam allows single cells to be imaged- sometimes in 3D! The ability to characterize single cells allows population diversity to be assessed and individual cells perhaps expressing a specific phenotype, to be targeted. Cultured single cell analysis is augmented by analysis of tumour models such as spheroids or organoids.

Photo: Single cells selected by fluorescence microscopy then profiled by multivariate analysis of the single cell lipidomics data.

We are part of the centre for antibiotic resistance research (CARe) at the University of Gothenburg where we use the surface sensitivity of the SIMS analysis to probe the chemistry of the bacterial envelope.

SIMS analysis can be extremely surface sensitive, producing signals from the upper few nanometers of a sample. This allows chemistry of the cell membrane to be probed selectively and by gradually eroding the sample using the ion beam changes in the membrane composition can be recorded as a function of depth. We are investigating how changes in the surface chemistry of bacteria can be related bacterial persistence and acquisition multi antibiotic resistance.

The use of gas cluster ion beams have not only increased the number of intact molecules that can be detected from a sample surface but also how many molecules remain intact during the depth profiling process. Historically only elements could be detected, this has gradually expanded through the introduction of C60 ion beams to small molecules and in our most recent work molecules with masses in excess of 2 kDa. were uncovered within the bacterial envelope.

Photo: a.) Gram-negative cell envelope. Adapted from www.memorangapp.com Retrieved: 20180523. b.) Mass spectrometry signals from different chemical species (a PG-lipid, Lipid A, ECACYC) a function of depth into the bacterial envelope.