Document text
Principal Investigator: RICHARD J TEMKIN
Organization: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Fiscal Year: 2024
Award: $518,992
Funding agency: National Institute of Biomedical Imaging and Bioengineering
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. Collectively, these advances will help
make DNP/NMR at high magnetic field a far more accessible and useful tool in modern biochemistry research.
Terms: <Amyloid><Amyloid Proteins><Amyloid Substance><Biochemistry><Biological><Biological Chemistry><Biomedical Research><Blood Plasma><Capsid Proteins><Cell Communication and Signaling><Cell Signaling><Coat Proteins><Communities><Complex><Coupled><Coupling><Devices><Electromagnetic Fields><Electromagnetic Fields Radiation><Electron Transport><Electrons><Frequencies><Generations><Guns><HIV-1><HIV-I><HIV1><Human Immunodeficiency Virus Type 1><Human immunodeficiency virus 1><International><Intracellular Communication and Signaling><Laser Electromagnetic><Laser Radiation><Lasers><Magic><Mediating><Membrane><Membrane Biology><Microwave Electromagnetic><Microwaves><Modernization><NMR Spectrometer><NMR Spectroscopy><Needles><Negative Beta Particle><Negatrons><Noise><Nuclear><Output><Phase><Physiologic pulse><Plasma><Plasma Serum><Power Sources><Power Supplies><Proteins><Pulse><RF coil><Research><Reticuloendothelial System, Serum, Plasma><Sampling><Semiconductors><Signal Transduction><Signal Transduction Systems><Signaling><Solid><Source><Speed><Structure><Surface><System><Techniques><Technology><Testing><Time><Training><Transmission><Viral Coat Proteins><Viral Outer Coat Protein><biologic><biological signal transduction><cost><data acquisition><data acquisitions><design><designing><electric field><electron transfer><experience><experiment><experimental research><experimental study><experiments><fabrication><falls><gun><improved><innovate><innovation><innovative><insight><instrumentation><magnetic field><membrane structure><microwave electromagnetic radiation><microwave radiation><millimeter><nano switch><nanosecond><nanoswitch><novel><nuclear magnetic resonance spectroscopy><programs><structural biology><time interval><tissue wound><tool><transmission process><voltage><wound><wounding><wounds>