Transient Metabolite Detection for Single-Cell Metabolomics and Diagnostics

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DESCRIPTION (Provided by the applicant) Abstract: This work will develop the capability to spatially detect a wide range of metabolites quantitatively and in real- time within a single cell. Few techniques are available to measure metabolite concentrations, although they are a key indicator of a cell's genomic expression, and the capability of metabolite flux measurements, resolved spatially and transiently, is heretofore unrealized. This project will provide these abilities to benefit several fields, including metabolomics, functional genomics, toxicology, cancer biology, metabolic engineering, and clinical diagnostics. The sensors will consist of single-walled carbon nanotubes which emit photostable near-infrared fluorescence which is highly environmentally sensitive. The nanotubes will be functionalized with ligands which bind to important metabolites and the binding event will be transduced by spectral shifts in the nanotube's emission. The investigator's group will introduce these nanotube sensors into live cells in order to answer important questions relevant to cancer biology and cell metabolism. Concomitantly, the team will work towards the rapid and real-time detection of clinically-relevant metabolites for early cancer diagnosis and the benchmarking of metastasis. We will also re-construct multiplexed metabolite data in order to conduct single- cell metabolomic fingerprinting. Public Health Relevance: Metabolites are small molecules produced in the body which may be used in the future to detect cancer at earlier stages, better understand the biology of cancer, and improve the development of important drugs. This project develops sensors using nanomaterials to detect many classes of metabolites within single cells and in human tissues.