Biomarker analysis (molecular imaging) of small samples using time-of-flight secondary ion mass spectrometry (ToF-SIMS)

Understanding the spatial distribution of lipid biomarkers at the microscopic scale may afford unprecedented insights into morphology - chemistry relations and contribute to better understanding of geobiological processes and biological sources of organic and inorganic molecules.

However, biomarkers are commonly analysed using extraction-based techniques (GC/MS, LC/MS), which brings about the loss of valuable spatial information during sample workup.

In cooperation with SP Technical Research Institute of Sweden, we use Time of Flight - Secondary Ion Mass Spectrometry (ToF-SIMS) as a means of analysing biomarkers directly on microscopic samples, i.e. without extraction, chromatography, derivatization, or heating. A pulsed primary ion beam is scanned in a raster pattern over the sample surface (Fig. 1). As a result, charged particles from the upper few monolayers are released. From these secondary ions, high-resolution mass spectra are produced. By quasi-continuously collecting a large number of mass spectra, a 'molecular map' of a sample area can be generated for any compound that produces a diagnostic ion in the spectrum.


Fig. 2 shows ToF-SIMS maps of archaeal lipids in a microbial mat retrieved from methane seeps in the Black Sea. On microscopic sections of these mats, individual microbial colonies can be distinguished by their different lipid biomarker fingerprints at a lateral resolution of < 5 µm.


ToF-SIMS is a quasi-non-destructive technique, thus allowing to subsequently examine the studied areas using conventional microscopic techniques. Further experiments are being conducted in order to establish ToF-SIMS as a tool for a wide range of geobiological applications that aim to detect and precisely localize organic compounds in environmental samples.


Selected publications

Leefmann T., Heim C., Kryvenda A., Siljeström S., Sjövall P., Thiel V. (2013): Biomarker imaging of single diatom cells in a microbial mat using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Organic Geochemistry 57, 23-33.


Lindgren J., Uvdal P., Sjövall P., Nilsson D.E., Engdahl A., Schultz B.P., Thiel V. (2012) Molecular preservation of the pigment melanin in fossil melanosomes. Nature Communications 3, 824 (doi:10.1038/ncomms1819). http://www.nature.com/ncomms/journal/v3/n5/abs/ncomms1819.html


Thiel V. and Sjövall, P. (2011) Using time-of-flight secondary ion mass spectrometry to study biomarkers. Annual Review of Earth and Planetary Sciences 39, 125-156. http://www.annualreviews.org/doi/abs/10.1146/annurev-earth-040610-133525


Thiel, V., Heim, C., Arp, G., Hahmann, U., Sjövall, P., Lausmaa, J. (2007): Biomarkers at the microscopic range: ToF-SIMS molecular imaging of Archaea-derived lipids in a microbial mat. Geobiology 5, 413-421. DOI:10.1111/j.1472-4669.2007.00119.x.

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picture: Fig. 1 Principle of ToF-SIMS picture: Fig. 2 Principle of ToF-SIMS