This paper demonstrates a previously unreported property of deoxyribonucleic acid-the ability of dye-labeled, solid-state DNA dried onto a surface to detect odors delivered in the vapor phase by changes in fluorescence. This property is useful for engineering systems to detect volatiles and provides a way for artificial sensors to emulate the way cross-reactive olfactory receptors respond to and encode single odorous compounds and mixtures. Recent studies show that the vertebrate olfactory receptor repertoire arises from an unusually large gene family and that the receptor types that have been tested so far show variable breadths of response. In designing biomimetic artificial noses, the challenge has been to generate a similarly large sensor repertoire that can be manufactured with exact chemical precision and reproducibility and that has the requisite combinatorial complexity to detect odors in the real world. Here we describe an approach for generating and screening large, diverse libraries of defined sensors using single-stranded, fluorescent dye-labeled DNA that has been dried onto a substrate and pulsed with brief exposures to different odors. These new solid-state DNA-based sensors are sensitive and show differential, sequence-dependent responses. Furthermore, we show that large DNA-based sensor libraries can be rapidly screened for odor response diversity using standard high-throughput microarray methods. These observations describe new properties of DNA and provide a generalized approach for producing explicitly tailored sensor arrays that can be rationally chosen for the detection of target volatiles with different chemical structures that include biologically derived odors, toxic chemicals, and explosives.