Tof-SIMS and laser-SNMS are becoming increasingly important tools for analysing the elemental and molecular distribution in biological samples. We have developed the prototype of an in-vacuum cryosectioning instrument directly attached to a ToF-SIMS/laser-SNMS instrument, which allows preparing and analyzing frozen non-dehydrated biological samples. Due to unavoidable effects during the handling, storing, and preparation of frozen samples, even inside the vacuum, it must be ensured that the analyzed surface is from the sample and not a preparation artefact. To this effect, a model structure, similar to the biological samples and with a defined chemical composition, was analyzed under varying thermal treatment before and during analysis, respectively, in order to identify a balance between evaporating and subliming adsorbed materials and the effect of freeze-drying on the measured signal. (c) 2006 Elsevier B.V. All rights reserved.