Methods and devices are provided for using high-density arrays of diverse chemical entities. In preferred embodiments, small volumes of multiple liquids are delivered to multiple reaction sites on a single substrate where the liquids are constrained to localized reaction sites. The substrate need not be cut apart prior to being used for analysis. Accordingly, the area of the substrate on which analysis may be performed is maximized. In many embodiments of the present invention, constraining regions hinder the transport of liquids between adjacent reaction sites.