Abstract: A multi-tier approach for use in a detecting harmful agents conveyed by the air. In a first tier procedure, the air (in a structure or a predefined area) is continuously automatically screened at a plurality of different predefined locations by air sensors distributed in the area to be monitored. Each air sensor is configured to detect a potentially harmful substance that is carried by the air proximate the predefined location, to determine if a potentially harmful substance might be present, but need not identify a specific harmful substance. When a potentially harmful agent is identified by an air sensor in the first tier screening, a sample of the potential threat is collected, and a second tier procedure is initiated. The second tier procedure uses a manual test, such as a nucleic acid amplification and detection assay to detect any of a plurality of different specific threats in the sample.