Next generation nanomedicine will consist of nanoparticle-based therapies that target specific cell populations. Nanoparticle-based therapies have the potential to reduce the dangerous side effects of chemotherapy drugs (by targeted destruction of cancer cells) and combat diseases such as cystic fibrosis (by targeted delivery of genes to lung cells). Investigating how engineered particles interact with, are internalized, and/or are trafficked through, biological cells is critical to the success of these ventures. To detect nanoparticles inside statistically relevant populations of individual cells, we are developing an approach that builds on focused ion beam tomography, which can mill specific cells within complex cultures to reveal internalized metal nanoparticles. We are particularly interested in strategies that create cellular contrast in the scanning electron microscope, but maintain nanoparticle contrast. Proposals could also be application focused; one example is designing particles that accumulate in different cellular compartments. A variety of optical and electron microscopes are available for this research.