Sample preparation for 3D SIMS chemical imaging of cells

Abstract

Time-of-fl ight secondary ion mass spectrometry (ToF-SIMS) is an emerging technique for the characterization ofbiological systems. With the development of novel ion sources such as cluster ion beams, ionizationeffi ciency has been increased, allowing for greater amounts of information to be obtained from the sampleof interest. This enables the plotting of the distribution of chemical compounds against position withsubmicrometer resolution, yielding a chemical map of the material. In addition, by combining imagingwith molecular depth profi ling, a complete 3-dimensional rendering of the object is possible. The study ofsingle biological cells presents signifi cant challenges due to the fundamental complexity associated with anybiological material. Sample preparation is of critical importance in controlling this complexity, owing tothe fragile nature of biological cells and to the need to characterize them in their native state, free ofchemical or physical changes. Here, we describe the four most widely used sample preparation methods forcellular imaging using ToF-SIMS, and provide guidance for data collection and analysis procedures.