Sometimes, for technical reasons (lack of sensitivity), it will be impossible to visualize active deposition and penetration in the skin or other biological tissues using FTIR microscopy, confocal Raman microscopy, or fluorescence microscopy. In these instances, Time of Flight Secondary Ion Mass Spectroscopy (TOF-SIMS) microscopy might offer a suitable alternative. TOF-SIMS microscopy is not reliant on topical actives having distinct IR or Raman absorption bands and doesn’t usually require the attachment of any markers or tags.

TOF-SIMS can be used to perform molecular component analysis as well as elemental analysis at the surface of biomaterials. By sectioning skin sample, the 2D distributions of specific molecular species in the different skin layers can be imaged.