Bright and Fast Sensors for Radioluminescence Microscopy of Single Living Cells

用于单个活细胞放射发光显微镜的明亮且快速的传感器

基本信息

批准号：
9267506
负责人：
STUART R MILLER
金额：
$ 72.3万
依托单位：
RADIATION MONITORING DEVICES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9267506
关键词：
ADME Study Address Affect Avidity Basic Science Behavior Beta Particle Biological Biological Sciences Cancer Biology Cell Culture Techniques Cell Cycle Cells Cellular Morphology Characteristics Chemicals Clinical Coupled Data Deposition Detection Development Disease Disease Pathway Drug resistance Electrons Environment Europium Evaluation Evolution Failure Feasibility Studies Feedback Film Gene Expression Goals Head and Neck Surgery Hematology Heterogeneity Hospitals Image Image Enhancement Immune In Situ Individual Institutional Review Boards Interphase Cell Ions Laboratories Light Lutetium Malignant Neoplasms Malignant neoplasm of thyroid Measurement Measures Methods Microscope Microscopy Molecular Morphology Noise Optics Otolaryngology Output Oxides Performance Pharmaceutical Preparations Phase Photons Play Population Positron-Emission Tomography Process Product Approvals Property Protocols documentation Radioactive Radioactive Iodine Radioisotopes Radiolabeled Radionuclide Imaging Radiopharmaceuticals Research Research Personnel Resistance Resolution Roentgen Rays Role Safety Sampling Sensitivity and Specificity Signal Transduction Specimen Spectrum Analysis Stable Isotope Labeling Standardization Stem cells Surface System Techniques Technology Testing Therapeutic Thick Thinness Tissues Transport Process Universities Variant Work X ray diffraction analysis X-Ray Diffraction absorption analog behavioral study biomaterial compatibility cancer stem cell cell injury cellular imaging charge coupled device camera clinical diagnostics cost density design evaporation experimental study fluorescence microscope fluorodeoxyglucose imaging modality imaging system improved innovation innovative technologies instrument ionization luminescence medical schools microscopic imaging mid-career faculty molecular imaging neoplastic cell next generation nuclear imaging oncology public health relevance quantum radiotracer reconstruction remediation response sensor small molecule success technological innovation thyroid neoplasm tool tumor uptake usability

项目摘要

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.

描述（由申请人提供）：放射发光显微镜（RLM）是一种新开发的用于对活单细胞中放射性核素摄取进行成像的方法，目前的放射性示踪剂成像方法仅限于测量大细胞群体中的平均放射性示踪剂摄取，因此缺乏。然而，利用新的放射发光显微镜技术，可以在荧光显微镜中可视化单个细胞内放射性示踪剂的吸收。该项目的目标是对该技术中使用的关键部件进行革命性创新，该关键部件是将电离 β 辐射转换为 CCD 相机成像的光学光子的闪烁体。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。提供一种表征单个细胞特有特性（例如基因表达、细胞周期、细胞损伤和细胞形态）如何影响放射性示踪剂的吸收和保留的方法更高的空间分辨率将允许在致密组织中原位探测单个细胞。切片，并将显着提高仪器的吞吐量，允许同时对数千个细胞进行成像，这些新功能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。在第一阶段是成功地证明了新型高密度透明闪烁体薄膜——铕激活氧化镥（Lu2O3:Eu）对 RLM 性能的显着改进。这种材料具有所有已知闪烁体中最高的密度（9.5 g/cm3），高效原子。数量（67.3）、出色的光输出和发射波长（610 nm），使硅传感器具有非常高的量子效率。放射发光显微镜提高了我们方法的性能和可行性，我们的最终目标是将这项技术作为放射发光成像皿商业化，该成像皿将具有标准的外形尺寸，但将包括 Lu2O3:Eu 闪烁体的薄涂层。因此，这项技术创新将为研究人员提供一种有价值的新工具，使放射性示踪剂的摄取能够前所未有地定位到单个活细胞，这种新的创新技术将作为当前使用的荧光显微镜仪器的补充得到广泛应用。因而将具有巨大的商业潜力。