The capability to analyze cellular uptake of physiological and pharmacological compounds with increasing sensitivity and temporal resolution plays a critical role in understanding the underlying molecular pathways involved in human diseases and disorders. Among the most challenging analytes are those present at very low concentrations with high temporal variability, and small molecules lacking moieties amenable for optical and/or electrochemical detection. Radioisotopes (RI) facilitate highly sensitive detection of these analytes, with minimal perturbation of analyte mass and structure, compared to fluorescent labels and other molecular tags. β-particle emitters, including 32P, 33P, 35S, and 3H are commonly used as biological tracers due to the prevalence of these atoms in biological molecules. Despite the advent of new molecular analysis approaches, RI remain the gold standard in a wide range of quantitative biological, chemical and environmental studies. RI labels have played a critical role in the investigation of biological systems, for almost a century. Though new analytical approaches, including mass spectrometry, now allow sensitive detection of label-free mixtures, the high mass sensitivity of radioassays is unparalleled, making radioassays indispensable for a range of biochemical and biomedical studies. Furthermore, improved detection capabilities that enable a broader application of RI detection to new biomedical research questions should prove transformational in high sensitivity biomolecular analyses. In this SBIR application, we propose to continue development of proprietary, IP-protected, innovative core-shell nanomaterials capable of real-time, and in some cases, molecularly selective, detection of low energy RIs directly in aqueous samples. These nanomaterials be demonstrated for intracellular measurement of low energy RI- labeled analytes. Such measurements would seed new research investigations and would position Scintillation Nanotechnologies INC as the only commercial entity providing products that perform such measurements.