Recent events showing the willingness of terrorist organizations and rogue states to consider biological weapons of mass destruction have underscored the need for rapid means to identify these agents. In particular, first responders entering a scene where biological agents may have been dispersed must have the tools necessary to characterize bioweapons in aerosols and in complex liquid or solid matrices. Existing rapid methods of bioanalysis relying upon polymerase chain reaction (PCR), gene chips, and protein and antibody arrays require substantial sample preparation to provide consistent results in the face of interferences, contaminants and inhibitors that are present in ambient air and water and samples eluted from solid surfaces. This proposal suggests the use of atmospheric electrospray ionization in conjunction with nanoparticle enhancement of separation efficiency as a means of high-throughput sample preparation. The innovation of the proposed biological sample processing system is the combination of electrospray ionization in the presence of functionalized nanoparticles with downstream magnetic charge-based and mass-based separation to provide selective concentration and purification of biological materials. The Phase I Technical Objectives include design and fabrication of a laboratory electrospray processing system having downstream electrostatic and magnetostatic separation, evaluation of the effect of magnetic and high-charge density nanoparticle additives on the efficiency of biomolecule purification and concentration, and acquisition of families of test data using simulated biological samples for use in optimization of a proof-of-concept prototype system. In Phase II, test procedures will be automated and miniaturized for further development in the Phase III commercialization segment of the program. Successful completion of the Phase I program will result in the demonstration of electrospray techniques for processing biological samples from various matrices. The processing system will find commercial use in biomedical evaluation of infectious diseases, environmental chemical analysis and food processing