Powerful Solid-State Sources to Enable Advanced EPR and DNP-NMR Measurements

VDI Project Summary AbstractThe NIH Division of Cell Biology and Biophysics supports studies of the biological macromolecules that affect the function and structure of living cellsand often play a role in diseaseWithin the realm of biophysicsone of the most important tools to study the structure and interactions of these molecules is nuclear magnetic resonanceNMRFor exampleNMR has been used to study the oligomeric forms of amyloidthat are that are critical to understanding the development of Alzheimerandapos s diseaseAlsoNMR allows study of the structure of membrane proteins for use as potential pharmaceutical targetsClearyNMR is an extremely powerful scientific toolhoweverthe technique is not simple and the measurements can be expensive and time consumingThis is primarily because the NMR signal is weak and requires sensitive receivers and long integration times for reliable detectionWithin the field of NMRdynamic nuclear polarizationDNPis a well known technique to greatly increase the signal strengthMost DNP systems rely on a Gyrotron to generate the required microwave powerAlthough Gyrotrons generate sufficient powerthey are incapable of generating the short pulses and modulated signals desired for advanced DNP systemsAlsotheir cost is prohibitive for all but the most well funded laboratoriesThe key focus of this project is to advance solid stateSSsource technology to the point where it can begin to replace the Gyrotrons for a significant proportion of DNP NMR measurementsthereby lowering the barriers to entry into this field and accelerating the pace of scientific discoveryThe Phase I effort is focused on demonstrating that recent technological innovations can be used to significantly increase the power and functionality of the SS sources for DNPThe first objective is to demonstrate an innovative frequency doubler design that is expected to generate greater thanmW atGHzThis is a significant milestone not only because it will increase the range of measurements possible with a SS sourcebut also because it is sufficient to fully pump the emerging traveling wave tubeTWTamplifierswhich can increase the power to the several wattsThe second objective is to generate short pulses and complex waveforms with accurate phase and frequency modulationThis is an important milestone because such control of the microwave signal can significantly increase the NMR signal without requiring increased powerThe final Phase I objective is to develop the general research plan for Phase II that will lead to watt level power atGHzextension of the technology to other frequencies of interestand the implementation of the pulse and modulation controls into a system optimized for DNPNMR research VDI Project NarrativeThe purpose of this research is to develop a solid state source technology that will enableadvanced DNP NMR and pulsed EPR systems with higher operating frequencies and improvedmodulation schemeswhile also reducing the cost and complexity of the systemsPulsed EPRand DNP NMR systems are being used to gain greater knowledge of the atomic level structuraldetail of biological moleculesand particularly proteinsat a speed that has not previously beenpossibleThusthis effort will facilitate the mission of the Division of Cell Biology and Biophysicstobetter understand the basic structures and processes in living cellsand lay the foundationfor ways to preventtreat and cure diseases that result from disturbed or abnormal cellularactivity