After 18 months of extensive testing and evaluation, the US Postal Service has made a decision to deploy automatic bio-threat detection systems in mail sorting facilities throughout the United States. A team, including Northrop Grumman, Cepheid, Smiths Detection, and Sceptor has developed this system called BDS (Bio Detection System). The BDS system will be the first and only automated, nationwide bio-threat detection system approved through rigorous testing of stringent systems requirements. The highest possible detection sensitivity is achieved by using the polymerase chain reaction (PCR), which is increasingly becoming the "gold standard" for biological detection and identification; oftentimes better than culturing. The lowest possible false positivity rate is achieved by extensive internal controls and assay validation procedures. Some aspects of the performance of the BDS system actually exceeds that of the US blood banking system for pathogen detection. Yet, all of this sophisticated, state-of-the-art biological processing is performed completely automatically, in a dusty, industrial environment in about 30 minutes. This presentation will describe the advanced fluidic, biological, chemical, and engineering aspects of this revolutionary technology. We will also discuss how a key sub-system of the BDS, the GeneXpert, is being applied to many other biomedical applications such as the detection of infectious diseases and cancer.