TR&D Project 2: Tissue and cellular elemental distribution, and image correlation

项目摘要-研发项目2 组织和细胞元素分布与图像相关性 该技术研发项目将发展扫描X射线荧光显微技术 (SFXM)，用于定量查看细胞和组织中的微量元素分布。它将使用低温样品 制备和成像条件作为化学和结构保存的金标准以及 抗辐射损伤。我们将开发低温SXFM功能，使可访问性增加100倍 阿贡国家实验室先进光子源(APS)光束线8-BM的样本区，以及 为其运作提供支持。这将使APS低温SXFM的可用实验时间增加一倍， 通过免费、同行评审的通用用户在我们的BTRR和其他生物医学研究人员之间进行划分 向APS提交的建议。 我们还将介绍低温样品与NIH的纳米级SFXM能力的交叉兼容性- 在APS购买了BionanoProbe，激光消融电感耦合等离子体质谱(LA-ICP-MS) 西北大学的MS；研发1)，西北大学的光声显微镜(PAM；研发2)，以及相关 APS的低温共聚焦显微镜(C3LM)。 我们将开发并提供PyElements，这是一个软件平台，可提供集成和跨 所有这些医疗设备的定量图像的注册视图。我们将在PyElements中整合 修正较厚样品中x射线荧光自吸收的数值优化方法，因此 人们甚至可以从更厚的3D样品中获得定量信息。所有这些发展都将 在我们推动生物医学项目的背景下进行，特别是大面积低温SXFM 主题A(大脑功能中的金属稳态或失调)、主题C(金属熔剂控制)的重要性 生殖和发育)和主题D(代谢病理学中的金属失衡)。

PROJECT SUMMARY - TR&D PROJECT 2 Tissue and Cellular Elemental Distribution, and Image Correlation This Technology Research and Development Project will develop Scanning X-Ray Fluorescence Microscopy (SFXM) for quantitative views of trace element distributions in cells and tissues. It will use cryogenic specimen preparation and imaging conditions as a gold standard for chemical and structural preservation as well as radiation damage resistance. We will develop a cryo SXFM capability with a hundredfold increase in accessible specimen area for beamline 8-BM of the Advanced Photon Source (APS) at Argonne National Laboratory, and provide support for its operation. This will double the accessible experimental time in cryo SXFM at the APS, divided between our BTRR and other biomedical researchers via no-cost, peer-reviewed General User Proposals to the APS. We will also introduce cryo specimen cross-compatibility with the nanoscale SFXM capabilities of the NIH- purchased Bionanoprobe at the APS, laser-ablation inductively coupled plasma mass spectrometry (LA-ICP- MS; TR&D 1) at Northwestern, photoacoustic microscopy (PAM; TR&D 2) at Northwestern, and correlative cryogenic confocal light microscope (C3LM) at the APS. We will develop and make available PyElements, a software platform to provide an integrated and cross- registered view of quantitative images from all of these modalities. We will incorporate into PyElements a numerical optimization approach to correcting for self-absorption of x-ray fluorescence in thicker specimens, so that one can obtain quantitative information even from thicker specimens in 3D. All of these developments will take place in the context of our Driving Biomedical Projects, with large-area cryo SXFM being of particular importance to Theme A (Metal homeostasis or dysregulation in brain function), Theme C (Metal fluxes controlling reproduction and development), and Theme D (Metal imbalances in metabolic pathology).