The interaction of insulin with polymeric coatings, commonly used in devices for insulin storage and administration, is affected by relative humidity (RH). Understanding the effect of RH on adhesion of insulin particles to polymeric surfaces is of particular interest for selecting coating materials and environmental conditions for packaging and storage. A custom humidity control system was constructed for use with the fluid cell cantilever holder for a Nanoscope model II atomic force microscope (AFM). This system was used for controlling the RH with a precision of +/- 1% over a range of similar to 0-100% and for making pull-off force measurements as a function of RH. Pull-off forces were measured between insulin particles attached to the end of an AFM cantilever and acrylonitrile-butadiene-styrene and polypropylene polymers. Two critical transitions indicated by sudden increases in the pull-off force were identified at two RH values. The first transition to higher pull-off force values occurred near 15-25% RH and the second transition occurred near 60 to 65% RH. The increasing adhesion force with increasing RH is mainly attributed to surface roughness effects that facilitate the formation of water bridges between insulin particle and the polymer substrate. (C) Koninklijke Brill NV, Leiden, 2011