We are developing reference test methods in collaboration with NIOSH, FDA and NCI for quantifying the physical, chemical and biological properties of nanoparticles (used for therapeutics, diagnosis and imaging) in synthetic and natural biofluidic environments such as lung fluid. X-ray, light scattering, MALDI, and XPS are the key measurement tools being developed for the complex task of solution characterization of nanoparticles in biofluids where nanoparticles can interact with macromolecules like proteins and lipids. To measure nanoparticle interactions in a biomimetic environment of oil and water, we have developed a platform known as Fossilized Liquid Assembly. We are also developing quantitative measures of cellular uptake of nanoparticles and methods to assess the cytotoxicity pathways that ultimately destroy cellular mechanisms. Nanoparticles being investigated include Quantum Dots, Gold, TiO2, SWCNT and Iron Oxide. NIST Gold nanoparticle Reference Material (RM) are currently available and SWCNT is being developed in this NIST wide effort.