MALDI mass spectrometry for rapid detection and characterization of biological threats

The Chemical/Biological Time-of-Flight (CB-TOF) is an end-to-end mass spectrometry-based system for rapid triage of "white powder" potential biological and chemical threats. CB-TOF utilizes matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) as an analytical tool to detect and characterize intact microorganisms and biotoxins (e.g., Bacillus anthracis spores and ricin, respectively) in less than 35 minutes. The system includes a robotic station for rapid, repeatable sample preparation for MALDI MS, a commercial laser desorption time-of-flight mass spectrometer, and novel detection algorithms, combined with a high-level technician-friendly graphical interface. The algorithms for bio-threat detection and presumptive identification are based on both empirical MS signatures and available proteomic database information. A large number of samples of appropriate bio-threat simulants have been examined, allowing characterization of the CB-TOF system performance, e.g., probabilities of detection and false positive rates, and differentiation of spore near-neighbors in a blind study. Confirmation of initial spore presumptive identification has been achieved through growth and vegetative biomarker detection. The transferability of CB-TOF protocols and database signatures to other laboratories has been evaluated as well.