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Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a rapidly developing technique for the characterization of a wide range of materials. Recently, advances in instrumentation and sample preparation approaches have provided the ability to perform 3D molecular imaging experiments. Polyatomic ion beams, such as C, and gas cluster ion beams, often Ar (n = 500–4000), substantially reduce the subsurface damage accumulation associated with continued bombardment of organic samples with atomic beams. In this review, the capabilities of the technique are discussed and examples of the 3D imaging approach for the analysis of model membrane systems, plant single cell, and tissue samples are presented. Ongoing challenges for 3D ToF-SIMS imaging are also discussed along with recent developments that might offer improved 3D imaging prospects in the near future.


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