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The characterization of solids, surfaces and thin films has represented a great challenge in many fields and it has been faced by several disciplines, such as Material Science, Solid State Physics or Analytical Chemistry, among others. Furthermore, most of the developments achieved in nanotechnology have been inevitably linked to the availability of characterization techniques allowing a deep knowledge of the chemical composition, morphology and interfacial chemistry of multilayered samples in the sub-micron scale. In this context, secondary ion mass spectrometry (SIMS) has been consolidated as one of the most powerful techniques due to its outstanding capabilities in terms of sensitivity, specificity and spatial resolution, both lateral and in-depth resolutions.