Gas cluster ion beams (GCIBs) provide new opportunities for bioimaging and molecular depth profiling with secondary ion mass spectrometry (SIMS). These beams, consisting of clusters containing thousands of particles, initiate desorption of target molecules with high yield and minimal fragmentation. This review emphasizes the unique opportunities for implementing these sources, especially for bioimaging applications. Theoretical aspects of the cluster ion/solid interaction are developed to maximize conditions for successful mass spectrometry. In addition, the history of how GCIBs have become practical laboratory tools is reviewed. Special emphasis is placed on the versatility of these sources, as size, kinetic energy, and chemical composition can be varied easily to maximize lateral resolution, hopefully to less than 1 micron, and to maximize ionization efficiency. Recent examples of bioimaging applications are also presented.

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