Sensitivity and Specificity ofin SituBacterial Chain Reaction (BCR) in Detecting Sparse Human Tumor Cells in Peripheral Blood

Abstract We report here the development of bacterial chain reaction (BCR), a system using micro organisms as nanodevices to amplify and visualize signals from molecular bioprobes such as antibodies, binding proteins, lectins, and oligonucleotides. Unlike conventional enzyme-linked amplification systems in which the amount of enzyme is a constant parameter, in the BCR an enzyme (penicillinase) is used to trigger a proliferative chain reaction producing an exponential increase in enzyme. The detection limits and specificity of BCR were determined using a model system designed to detect and enumerate MCF-7 (a human breast adenocarcinoma cell line) cells disseminated at extremely low frequency (e.g., one tumor cell per million normal cells) among monocluclear cells (MNCs) of human peripheral blood. Results of testing 83 specimens of peripheral blood from presumably healthy donors showed 97.6% specificity. The system was capable of detecting tumor cells at a frequency of 2 × 10 −7 .