Imaging mass spectrometry for novel insights into contact allergy - a proof-of-concept study on nickel

Background. In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. Objectives. To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. Method. Full-thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type diffusion cells. Biopsies were obtained from nickel-treated samples and control (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating high-resolution images of ion distribution in the epidermis and upper dermis. Results. The skin layers could be discerned from the ToF-SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. Conclusions. This is the first time that ToF-SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general