The long-term goal of this research is to establish the chain of molecular events associated with (1) neurotransmitter release at the single cell and subcellular level and (2) with cell differentiation and reprogramming. These are incredibly important goals for which there are few analytical chemistry methods that are available and useful. The immediate goal therefore includes development of three chemical methodologies at the cutting edge of analytical chemistry: 1) the development of arrays of nanometer electrodes that can be used to spatially measure the release of easily oxidized substances across the cell surface; 2) to improve the combination of MALDI and cluster SIMS ion sources on an orthogonal QStar instrument to enable protein and glycoprotein analysis at the single whole cell level, lipid domain analysis at the subcellular level, and importantly, depth profiling; and 3) the application of information discovered at single cells and of the methods developed in goals 1 and 2 to an in vitro model of cell-to-cell communication and regeneration. I intend to build on my expertise in both electrochemistry and SIMS imaging to develop these approaches. The work described here constitutes two new directions of research in my group as well as new analytical chemistry, and, if successful, will lead to researchers being able to gather incredibly important new data about cell-to-cell communication and cell differentiation and reprogramming as well as to a better understanding the role of lipids in exocytosis and endocytosis.