an improved microfabricated apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described . the apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions . the apparatus is characterized by discrete and isolated regions that extend through said substrate and terminate on a second surface thereof such that when a test sample is allowed to the substrate , it is capable of penetrating through each such region during the course of said binding reaction . the apparatus is especially useful for sequencing by hybridization of dna molecules .