Sample Preparation of Biological Tissues and Cells for the Time-of-Flight Secondary Ion Mass Spectrometry

The review is devoted to the application of time-of-flight secondary ion mass spectrometry (ToF–SIMS) to the analysis of biological tissues and cells. The invention of cluster primary ions significantly improved the sensitivity, especially in the mass range above several hundred of Daltons, which opened up the study of lipids, amino acids, nucleic acids, metabolites, and drugs. As other methods based on the bombardment of sample surface with a particle beam, ToF–SIMS measurements are carried out under ultrahigh vacuum conditions, which makes sample preparation of biological materials a critical stage of the experiment. Several techniques have been developed for preparing single cells, cell cultures, and tissues for the analysis. Most of them are based on conventional techniques used in histology and cytology, including optical, electron, probe microscopy and electron probe microanalysis. However, the analytical features of ToF–SIMS make it necessary to adapt these techniques. A universal solution does not exist, and the main objective of this review was to systematize and compare the developed techniques of the sample preparation for ToF–SIMS. The effect of instrumental factors on the results of the ToF–SIMS analysis of biological samples was also reported.