Development of a Narrow Bore Cryogenic MAS NMR Probe and EPR spectrometer for DNP Enhanced MAS NMR

Project SummarySolid state Nuclear Magnetic ResonancessNMRis a provenpowerful tool for discerning structural features of macromolecular complexes important in a wide array of human disease statesThe method has contributed to advances in our understanding of Alzheimerandapos sParkinsonandapos sand prion diseasesand the molecular basis of bacterial antibiotic resistanceIn the past decade the use of dynamic nuclear polarizationDNPto enhance the sensitivity of these experiments byfoldand thus increase throughput byorders of magnitude has resulted in a revolution in the range of biological questions that can be addressed with this methodAt present DNP enhanced ssNMR requires a wide bore NMR magneta cryogenic ssNMR probe for magic angle spinningMASand a high power gyrotron microwave sourceThis represents a capital investment in laboratory space and equipment not accessible to most institutionsnot to mention the high operating costs for cryogenic MAS probesIn this development program we will realize an implementation of DNP enhanced MAS NMR instrumentation in which the cost of ownership is so significantly reduced as to be accessible to single investigator laboratoriesThe system to be demonstrated for commercialization will replace the wide bore NMR magnet with a ubiquitous and less expensive standard bore magnetand employ a frequency agile diode based mm wave source less thanthe cost of a gyrotronIt will also reduce helium cryogen operating costs by recovering the helium used via adaptation to a standard NMR laboratory helium recovery systemInnovations in quasioptical microwave power delivery in combination with smaller MAS rotors will provide the same DNP performance as current gyrotron based systems by more effectively focusing the available power to a similar power density and delivering this to the sampleBy increasing the accessibility of DNP enhanced MAS NMR these innovations are expected to accelerate research into the molecular structural basis of a wide array of human disease states Project NarrativeA number of the most important challenges in human health ranging from Alzheimerandapos s disease to bacterial antibiotic resistance require structural characterization of complex macromolecular assemblies in order to understand the molecular basis of causationand thereby strategies for curative treatmentsSolid state magnetic resonance is especially effective in obtaining such dataand the recent addition of dynamic nuclear polarization can accelerate thistofoldThis project will develop a new class of instrumentation that by virtue of an order magnitude lower acquisition and operating cost will result in more widespread applicationand thereby greatly accelerate the research aimed at solving these important problems in human health and disease