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

微量元素(以百万分之几的水平存在)在几乎所有的生物过程中都发挥着关键作用；它们对生命是必不可少的，但如果存在的浓度不合适，也可能是有毒的。因此，细胞内的微量元素水平往往受到严格的调控，有一套复杂的机制来控制细胞的“无机生理”，即微量元素的调节、吸收、储存和外流。虽然有许多关于生物学中的微量元素的研究，但几乎所有的研究都依赖于批量分析(例如，在一组细胞中平均存在多少金属；以及这种变化是如何作为化学和/或生物处理的函数的？)。即将开发的新仪器将允许直接测定完好的单个细胞中的微量元素浓度。该仪器将首次方便地确定单个细胞的无机成分，从而提供对种群内成分分布的直接洞察，并允许进行旨在将其他细胞属性与化学成分相关联的研究。通过不仅可以测定平均浓度，而且还可以测定单个浓度中细胞间的变化，并允许这些数据与细胞状态的常规测量相关联，这将提供一种转变能力，打开了以前所未有的水平剖析必需和有毒微量元素的细胞作用的可能性。

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