Most of the ID vaccination methods described so far involve minimally invasive needle-based methods or non-invasive jet-based methods that actively deposit vaccine within the skin. Another set of approaches involve mostly non-invasive methods that increase skin permeability to enable vaccine transport into the skin in a transiently permeabilized state. The key to success using these approaches is disruption of skin's outer layer, called stratum corneum. Although the stratum corneum is only 10-20 lm thick, it provides a highly effective barrier to the permeation of xenogens, including topically applied vaccine formulations (Scheuplein and Blank 1971) . A number of methods to increase skin permeability have been developed, largely for drug delivery applications, many of which have been tested for vaccination (Mitragotri 2005; Prausnitz and Langer 2008) .