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：
9135873
负责人：
STUART R MILLER
金额：
$ 75.32万
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 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9135873
关键词：
ADME Study Address Affect Avidity Basic Science Behavior Beta Particle Biological Sciences Cancer Biology Cell Culture Techniques Cell Cycle Cells Cellular Morphology Characteristics Chemicals Clinical Coupled Data Deposition Detection Development Diagnostic Disease Disease Pathway Drug resistance Electrons Environment Equilibrium Europium Evaluation Evolution Failure Feasibility Studies Feedback Film Gene Expression Goals Head and Neck Surgery Hematology Heterogeneity Hospitals Image Immune In Situ Individual Institutional Review Boards Interphase Cell Label Laboratories Life Light Lutetium Malignant Neoplasms Malignant neoplasm of thyroid Measurement Measures Methods Microscope Microscopy Molecular Morphology Noise Nuclear 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 Stem cells Surface System Techniques Technology Testing Therapeutic Thick 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 cost density design evaporation fluorescence microscope fluorodeoxyglucose imaging modality imaging system improved innovation innovative technologies instrument ionization luminescence medical schools meetings microscopic imaging mid-career faculty molecular imaging neoplastic cell next generation oncology public health relevance quantum radiotracer reconstruction remediation research study 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（由适用提供）：放射发光显微镜（RLM）是一种新开发的方法，用于对活单细胞中的放射性摄取进行成像。当前的放射性示意剂成像方法仅限于测量大细胞群体中的平均放射性示意剂摄取，因此缺乏量化细胞间变化的能力。但是，使用新的发光显微镜技术，可以在荧光显微镜环境中可视化单个细胞内的放射性示意剂的吸收。该项目的目的是在此技术中使用的关键组件中开发革命性的创新。辐射发光显微镜成像系统中的这个关键部分是将电离β辐射转换为使用CCD摄像机成像的光学照片的闪光灯。在这项工作中，将开发改进的闪光灯，专门用于用于辐射发光显微镜系统，该系统将提供前所未有的灵敏度和空间分辨率。这种技术进步具有在研究和医院中使用宽度的潜力，提供了一种表征对单个细胞特异性特定的特异性（例如基因表达，细胞周期，细胞损伤和CEL形态）如何影响放射性示踪剂的摄取和保留的方法。较高的空间分辨率将允许在密集的组织切片中原位探测单个细胞，并将显着改善仪器的吞吐量，从而立即将数千个细胞成像。这些新功能对于帮助研究人员更好地了解罕见的单个CELS（例如干细胞或耐药细胞）的行为至关重要。 I期间的工作成功地证明了新型高度致密透明闪烁体的薄膜，Europium激活的氧化lutetium（Lu2O3：eu）的薄膜显着改善。该材料的密度最高（9.5 g/cm3）的任何已知闪光灯，高效原子数（67.3），出色的光输出和发射波长（610 nm），SI传感器具有很高的量子效率。将闪烁体的标本集成到辐射显微镜中，表明性能的提高和方法的可行性。我们的最终目标是将这项技术作为启用放射性发光的成像菜进行商业化，该菜肴将具有标准的外形，但将包括Lu2O3的薄涂层：EU Scintillator 在底部。因此，技术创新将为研究人员提供一个有价值的新工具，从而使放射性示意剂摄取的前所未有的定位降低到单个活细胞。这项新的创新技术将在当今使用的当前荧光显微镜仪器中使用宽度，因此具有巨大的商业潜力。