Bright and Fast Sensors for Radioluminescence Microscopy of Single Living Cells

 描述(申请人提供)：放射发光显微镜(RLM)是一种新开发的活体单细胞放射性核素摄取成像方法。目前的放射性示踪剂成像方法仅限于测量大细胞群中的平均放射性示踪剂摄取量，因此缺乏量化细胞间差异的能力。然而，使用新的射线发光显微镜技术，可以在荧光显微镜环境中可视化单个细胞内的放射性示踪剂摄取。该项目的目标是对这项技术中使用的关键部件进行革命性的创新。放射发光显微镜成像系统中的这个关键部分是闪烁体，它将电离的贝塔辐射转化为光学光子，并用ccd相机成像。在这项工作中，将开发一种改进的闪烁体，专门用于放射发光显微镜系统，该系统将提供前所未有的灵敏度和空间分辨率。这种技术进步有可能在研究和医院中广泛使用，提供了一种手段来表征个别细胞特有的属性(如基因表达、细胞周期、细胞损伤和细胞形态)如何影响放射性示踪剂的摄取和保留。更高的空间分辨率将允许在致密的组织切片中原位探测单个细胞，并将显著提高仪器的吞吐量，允许同时对数千个细胞进行成像。这些新能力对于帮助研究人员更好地了解干细胞或耐药细胞等稀有单细胞的行为至关重要。第一阶段的工作成功地展示了一种新的高密度透明闪烁体--Eu激活的氧化钚(Lu2O3：Eu)薄膜对RLM性能的显著改善。这种材料具有已知闪烁体中最高的密度(9.5g/cm3)、高有效原子序数(67.3)、出色的光输出以及硅传感器具有非常高量子效率的发射波长(610 Nm)。闪烁体样品被集成到放射发光显微镜中，展示了改进的性能和我们方法的可行性。我们的最终目标是将这项技术商业化，使其成为一种具有放射发光功能的成像碟片，它将具有标准的外形系数，但将包括一层薄薄的Lu2O3：Eu闪烁体涂层 在底部。因此，这项技术创新将为研究人员提供一个有价值的新工具，使放射性示踪剂摄取前所未有的本地化，一直延伸到单个活细胞。这项新的创新技术将作为目前使用的荧光显微镜仪器的补充而得到广泛使用，因此将具有巨大的商业潜力。

 DESCRIPTION (provided by applicant): Radioluminescence microscopy (RLM) is a newly developed method for imaging radionuclide uptake in live single cells. Current methods of radiotracer imaging are limited to measuring the average radiotracer uptake in large cell populations and, as a result, lack the ability to quantify cell-to-cell variations. With the new raio- luminescence microscopy technique, however, it is possible to visualize radiotracer uptake within individual cells in a fluorescence microscope environment. The goal of this project is to develop a revolutionary innovation in a key component used in this technique. This key part in the radioluminescence microscopy imaging system is the scintillator that converts ionizing beta radiation into optical photons that are imaged with a CCD camera. In this work, an improved scintillator will be developed, specifically for use in a radioluminescence microscopy system that will offer unprecedented sensitivity and spatial resolution. Such a technological advance has the potential for widespread use in research and in hospitals, providing a means to characterize how properties specific to individual cells (e.g. gene expression, cell cycle, cell damage, and cel morphology) affect the uptake and retention of radiotracers. Higher spatial resolution will allow single cells to be probed in situ, in dense tissue sections, and will dramatically improve the throughput of the instruments, allowing thousands of cells to be imaged at once. These new capabilities will be critical to help researchers better understand the behavior of rare single cels such as stem cells or drug-resistant cells. The work during Phase I was successful in demonstrating the significant RLM performance improvements with thin films of a new highly dense transparent scintillator, europium-activated lutetium oxide (Lu2O3:Eu). This material has the highest density (9.5 g/cm3) of any known scintillator, high effective atomic number (67.3), excellent light output, and an emission wavelength (610 nm) for which Si sensors have a very high quantum efficiency. Scintillator specimens were integrated into a radioluminescence microscope demonstrating improved performance and the feasibility of our approach. Our ultimate goal is to commercialize this technology as a radioluminescence-enabled imaging dish, which will have a standard form factor but will include a thin coating of the Lu2O3:Eu scintillator at the bottom. As such, the technological innovation will provide a valuable new tool to researchers allowing unprecedented localization of radiotracer uptake down to single living cells. This new innovative technology will have widespread use as an addition to current fluorescence microscope instruments in use today and thus will have great commercial potential.