Abstract: Micro-reactors for selective enhancement of ligands by exponential enrichment (ISOS) include a reactant chamber defined in a fluoropolymer. A target exposure aperture controls a surface area, crystal face or orientation and surface features of a target that is exposed to a random mixture of candidate molecules. The surface area of the target can be selected based on number or concentration of candidate species to enhance candidate competition. The target surface can be formed by deposition of a thin film of a target material on a rigid substrate such as a glass plate. Selected exposure areas are typically substantially smaller than a characteristic cross sectional area of a reactant chamber volume and can be at least as small as 0.1 mm2.