For biomedical systems, determining the chemical state (composition, molecular structure, and orientation) and distribution of biological moieties present on a surface is critical. Many important cells and tissue functions depend on the arrangement of molecules at their surfaces. Also, a central goal of modern bioengineering is the development of biomaterial surfaces that direct the biological healing response. These complex, novel surfaces are envisioned to have a well-defined array of recognition sites designed to interact specifically with cells. Thus, it is essential to develop surface analysis techniques capable of providing detailed surface chemical state information at high spatial resolutions. The IONTOF time-of-flight secondary ion mass spectrometry (ToF-SIMS) system requested in this application will provide essential, new capabilities for these studies. In the past 10 years instrumentation manufacturers have made significant advances in all areas of ToF-SIMS instrument performance that will benefit NIH-funded biomedical research. The specific improvements over our current ToF-SIMS systems that will be provided by the new IONTOF TOF.SIMS5 system with Bi and Ceo cluster ion beam sources are: 1) >10x increase in secondary ion yield for most samples; 2) >30% improvement in mass resolution; 3) molecular depth profiling for some organic and biological samples (not currently possible with the existing instruments); 4) increased sensitivity providing lower detection limits and shorter data acquisition times; 5) more efficient and easier to use charge neutralization system; 6) computer controlled sample stage; 7) latest software (data acquisition, data analysis, and spectral library with search engine) and 8) decreased instrument downtime. In the imaging mode ToF-SIMS provides detailed information about the molecular surface structure at a spatial resolutions of < 2 microns (high mass resolution mode) and <200 nm (low mass resolution mode). This information is essential for determining the structure-function relationship of a biomaterial surface to its biological activity. Relevant applications for ToF-SIMS analysis include biocompatibility of implants, biomolecule separations, cell culture, biosensors, bacterial-induced corrosion, ELISA assays, and DNA manipulations. Combining the new capabilities of the proposed ToF-SIMS system with the existing the University of Washington imaging electron spectroscopy for chemical analysis (ESCA) and scanning probe microscopy (SPM) systems will provide a powerful set of complementary biomedical surface analysis techniques that will make a significant contribution to NIH- funded biomedical research projects. Knowledge of the nature of biomedical implant surfaces and an understanding of how these surfaces direct biological processes is needed to permit the rational design of biomedical implants. The proposed ToF-SIMS instrument will help achieve this goal. ? ?