Desorption Electrospray Ionization (DESI) for Mass Spectrometry Based Imaging

我们身体的每个组织几乎每一个过程都会产生代谢物。目前测量这些代谢物的技术很粗糙，因为它们只允许研究人员知道特定组织中的量。这样做的问题是，组织本身是复杂的，因为它们包含许多不同类型的细胞，每种细胞都有不同的用途。我们要求将一台名为DESI源的复杂设备添加到我们实验室现有的质谱仪中。DESI源和质谱仪的结合将使多名研究人员能够可视化各种代谢物、脂质和神经递质在组织中的具体位置，这将使我们能够更多地了解这些代谢物在我们身体的各种组织中的作用。这是对目前技术的重大进步，因为我们将能够几乎研究我们所有主要器官正常运作期间产生的数千种代谢物中的任何一种。 这一基础设施将对许多研究项目有用。主要申请者研究体内的不同代谢物，以及它们如何调节身体处理(代谢和消除)药物的方式。人体处理药物的方式很重要，因为它在人群中存在很大差异。这导致一些人具有药物预期的有益效果，而另一些人则经历了不想要的毒副作用。基础设施将促进研究，使我们能够确定人体内任何器官的特定区域是如何受到代谢物水平相对于同一器官另一区域的影响的。这将有助于阐明为什么人群对药物的反应有很大差异的原因。 许多其他研究项目也将受益于所要求的基础设施。我们所要求的新的代谢物可视化工具将帮助我们了解当大脑随着时间的推移退化时会发生什么。它还将帮助我们了解母亲暴露在有毒化合物中对胎儿发育的影响，运动对代谢的特定有益影响，脊柱的代谢变化，以及多种代谢物水平如何随着细胞的生长而变化。

Metabolites are produced from nearly every process, in every tissue in our body. Current techniques to measure these metabolites are crude in that they allow researchers to know only the amount in a specific tissue. The problem with this is that tissues themselves are complex in that they contain many different cell types each with a different purpose. We are requesting a sophisticated piece of equipment called a DESI source to be added to a mass spectrometer that already exists in our lab. The combination of the DESI source and the mass spectrometer will allow multiple researchers to visualize the specific location of various metabolites, lipids and neurotransmitters in tissues which will allow us to learn more about what these metabolites are doing in various tissues in our body. This represents a major advance from current technologies as we will be able to investigate practically any of the thousands of metabolites produced during the normal functioning of all of our major organs. This infrastructure will be useful to many research programs. The principal applicant studies different metabolites in the body and how they regulate the way that the body handles (metabolizes and eliminates) drugs. The way the body handles drugs is important because it varies substantially amongst the population. This results in some people that have the intended beneficial effect of the drug while others experience unwanted toxic side effects. The infrastructure will facilitate studies that allow us determine how a particular area of any organ in the body is impacted by changes in metabolite levels compared to another area of the same organ. This will help elucidate the reasons why the population varies substantially in their response to medications. Many other research programs will benefit from the requested infrastructure as well. The new metabolite visualization tool we are requesting will help us learn what happens to the brain when it degenerates over time. It will also help us learn the impact of maternal exposure to toxic compounds on fetal development, the specific metabolic beneficial effects of exercise, metabolic changes in the spine, and how multiple levels of metabolites change as cells grow.