Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems

Mass spectrometry imaging (MSI) techniques are increasingly being used within many biological fields, including medicine, pathology, and microbial ecology. There are a variety of desorption/ionization methods used in these efforts to generate mass spectra and create ion images of samples of interest 1–4. Each of these MSI methods has their own virtues. Here, we focus on the surface-sensitive technique of secondary ion mass spectrometry (SIMS). Of the MSI methods available, SIMS offers the highest lateral resolution. Moreover, SIMS versatility in the number of different operating modes and types of mass spectrometers available has made it an increasingly popular method for bio-related measurements. Traditionally, SIMS has been most heavily used for inorganic semiconductor research, but with recent technologies it has grown in popularity for analysis of biologically relevant samples. In the SIMS technique, a focused ion beam is used to bombard a sample, ejecting and ionizing molecules from the sample surface that are subsequently analyzed in a mass spectrometer (Figure 1) 5. Currently, SIMS provides micrometer- to nanometer-scale lateral spatial resolution 6. To represent the range of analytical capabilities of SIMS, we focus in this article on three specific types of SIMS instrumentation (Figure 2): Fourier transform ion cyclotron resonance SIMS (FTICR-SIMS), time-of-flight SIMS (ToF-SIMS), and a specialized dynamic SIMS instrument (NanoSIMS), which offers the highest lateral image resolution of any MSI method. These instruments provide information at different dimensional scales that can be matched to the problem of interest.