Biopraxis proposes to develop its platform mu/SERS TM technology as a high-throughput biochip for screening large populations and large numbers of environmental samples for diverse chemical contaminants, including heavy metals, PCBs, pesticides, antibiotic residues, and naturally occurring toxins. Unlike other biochips, ?SERS TM does not rely on the use of labels to tell when binding takes place. Instead, spectral fingerprints are collected directly from each pixel on the chip, using surface-enhanced Raman scattering (SERS) microscopy. Because these fingerprints contain a rich body of information on the chemistries of the biomolecule and any target bound to it, mu/SERS TM can not only tell whether binding took place, but can tell which targets were bound, produce information on how they were bound (i.e., the binding chemistries involved), and even tell whether the biomolecule could have bound its targets, or had become denatured. Phase l showed that mu/SERS TM can analyze inorganic and organic contaminants, simultaneously, and individually identify cross-reactive sample constituents in complex 'real world' samples, without sample preparation or clean-up steps. In addition, Phase l showed that the program can also lead to a biochip to screen for synergistic interactions between toxic compounds, in vitro, at the molecular level; and to the identification of biomarkers that reflect exposure to mixtures of inorganic and organic contaminants. On Phase l, fingerprints were collected from sub-attomole to low-zeptomole amounts of bound targets. Phase II is designed to optimize key parameters, in order to (a)predict the sensitivity that can be achieved in terms of the amount of sample and target concentration that will be needed; and (b)confirm that mu/SERS TM products will be economical and practical for high-throughput analyses. The studies will also lay the foundation for developing methods to fabricate compact, high-density biochips; explore a new method for producing high affinity biomolecules that can be used with any biomolecule-based assay or sensor; and develop a body of information on a potential mechanism for synergistic toxic interactions, and the factors that can affect it.