IDBR: Development of an x-ray flow cytometer for single cell metal analysis

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Trace elements (those present at the parts-per-million level) play a critical role in virtually all biological processes; they are essential to life but can also be toxic if present at the wrong concentration. Consequently, the trace element levels within cells tend to be tightly regulated, with a complex set of machinery to control the "inorganic physiology" of cells, that is, the regulation, uptake, storage, and efflux of trace elements. Although there have been many studies of trace elements in biology, virtually all have relied on bulk analyses (e.g., how much metal is present on average in an ensemble of cells; and how does this change as a function of chemical and/or biological treatment?). The new instrument that will be developed will permit the direct determination of the concentrations of trace elements in intact individual cells. The instrument will allow, for the first time, facile determination of the inorganic composition of individual cells, thereby providing direct insight into the distribution of compositions within the population, and permitting studies aimed at correlating other cellular properties with chemical composition. By permitting determination of not only average concentrations but also the cell-to-cell variations in individual concentrations, and by allowing these data to be correlated with conventional measures of cell status, this will provide a transformative capability, opening the possibility of dissecting the cellular roles of both essential and toxic trace elements with an unprecedented level