Bright and Fast Sensors for Radioluminescence Microscopy of Single Living Cells

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 Lu O Eu This material has the highest density g cm of any known scintillator high effective atomic number excellent light output and an emission wavelength 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 Lu O 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 PUBLIC HEALTH RELEVANCE The goal of the proposed research is to develop a very high performance radioluminescence microscope for imaging radionuclide uptake in live single cells Among other benefits this 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 cell morphology affect the uptake and retention of radiotracers Because of the prominent role played by PET in oncology radioluminescence microscopy may also become a routine technique in cancer biology for instance to study the behavior of distinct cell subpopulations within a tumor such as the cancer stem cells or drug resistant cells In hematology the microscope could be used to characterize the properties of single immune cells Last this new technique will benefit the development of new imaging and therapeutic radiopharmaceuticals since it will allow researchers to more precisely measure the uptake of a radiopharmaceutical in single cells