High Throughput, High Sensitivity NMR

This proposal is to purchase equipment to convert an existing Nuclear Magnetic Resonance (NMR) spectrometer at the University of Manchester (UoM) so that it can be used for high-throughput (HTP) NMR with high sensitivity detection.The Manchester Institute of Biotechnology (MIB), where the instrument is housed, has a robotic liquid-handling Facility, necessary for the reproducible sample preparation required for HTP studies. NMR spectra can be used as a molecular fingerprint that is defined precisely by the structure of a chemical. Use of NMR to study mixtures of molecules is compromised partly by sensitivity, and also by (for 1H NMR) resolution. State of the art methodology developed in Manchester can solve some or all of these limitations. HTP studies of complex mixtures using sophisticated NMR techniques to increase sensitivity, resolution and/or specificity will allow definition of changes in chemical composition due to metabolism (in higher eukaryotes, media, water, or soil) or specific biocatalysts, or to screen small molecules for their effects on target proteins, either as drug-like molecules, or excipients. In addition, we will continue to use the equipment for structural and functional biomolecular NMR, to study proteins in solution. The research will impact on environmental and industrial biotechnology, enabling the transition to "net zero" carbon emissions and developing sustainable agriculture, and on biochemical research, enabling pharmaceutical development and consequently life-long health.

This proposal is to purchase equipment to convert an existing 800 MHz NMR spectrometer at the University of Manchester (UoM) so that it can be used for high-throughput (HTP) NMR with high sensitivity 1H, 19F and 13C detection. The necessary components are a helium-cooled 5mm TCI-H&F CryoProbe and a SampleJet autosampler, which allows the loading of SBS (Society for Biological Screening) standard footprint sample racks. The 800MHz NMR spectrometer is the highest field spectrometer at UoM and, as the highest resolution and sensitivity instrument, is the most suited for HTP work. In addition, the Manchester Institute of Biotechnology (MIB), where the instrument is housed, has a robotic liquid-handling Facility, necessary for the reproducible sample preparation required for HTP studies. HTP studies of complex mixtures using sophisticated NMR techniques to increase sensitivity, resolution and/or specificity will allow definition of changes in chemical composition due to metabolism (in higher eukaryotes, media, water, or soil) or specific biocatalysts, or to screen small molecules for their effects on target proteins, either as drug-like molecules, or excipients. In addition, we will continue to use the equipment for structural and functional biomolecular NMR, to study proteins in solution. The research will impact on environmental and industrial biotechnology, enabling the transition to "net zero" carbon emissions and developing sustainable agriculture, and on biochemical research, enabling pharmaceutical development and consequently life-long health.