The proposed research is focused on innovative instrumentation that will enable fundamental advances in the field of Dynamic Nuclear Polarization (DNP) NMR at high magnetic fields, making this powerful technique far more readily available and useful to the national and international biomedical research communities. In DNP NMR, a high frequency microwave source is used to irradiate electron - nuclear transitions, thereby transferring the high spin polarization in the electron spin reservoir to the nuclear spin system through hyperfine and dipolar interactions. The resulting enhancements in NMR signals dramatically reduce data acquisition times, and thus DNP NMR is now considered a major advance in NMR spectroscopy. Recently, new biological insights were obtained using DNP on highly complex systems like HIV-1 capsid proteins, needle-like structures from bacterial secretion systems or in-cell proteins. In DNP experiments at the high magnetic fields where contemporary NMR research is conducted, the required microwave frequency is in the terahertz (THz) regime: 460 GHz, 527 GHz and 593 GHz for g=2 electrons at 700 MHz, 800 MHz and 900 MHz 1H NMR frequencies respectively. However, the enhancement in the DNP NMR signal falls off rapidly with increasing magnetic field and correspondingly increasing microwave frequency. Time domain DNP techniques such as Nuclear Orientation via Electron Spin Locking (NOVEL), Time Optimized (TOP) DNP and the Integrated Solid Effect (ISE) do not fall off with increasing magnetic field and are thus very attractive at high magnetic fields. However, these techniques are currently limited to low magnetic field NMR spectrometers due to the lack of the high power, pulsed THz sources and instrumentation required to perform pulsed DNP experiments at high magnetic field. NOVEL requires large Rabi frequencies (>10 MHz) in pulses of a few nanoseconds. The required power levels are in the kilowatt range and are further exacerbated by the poor electromagnetic field coupling into the sample in the present-day magic angle spinning (MAS) sample holders. Our pioneering research will provide the instrumentation needed for high magnetic field DNP NMR by developing pulsed gyrotron oscillators capable of generating > 5 kW output power at 460 GHz and higher. We will also develop a laser driven semiconductor switch that will be used to form the nanosecond scale pulses needed for NOVEL experiments. For TOP DNP, we will use reflection of the gyrotron output to produce the required train of nanosecond scale pulses. We will demonstrate a frequency swept gyrotron source by using fast voltage control of the gyrotron’s electron gun to meet the requirements of ISE experiments. The proposed research will use available gyrotron magnets, power supplies and a 460 GHz DNP NMR spectrometer to speed up the research and reduce costs. The efficacy of these techniques will be demonstrated in DNP NMR experiments at 460 GHz using an available spectrometer. Collectiv...