For over three decades, High-Resolution (HR) Nuclear Magnetic Resonance (NMR) has been a leading analytical technique for structure and function elucidation of molecules of all types, large and small, in homogeneous systems. More recently, Magic Angle Spinning (MAS) has been combined with high-field HR-NMR to extend the technique to inhomogeneous systems, such as human and animal tissues. The 1H HR-MAS spectrum of malignant breast cancer tissue shows dramatically increased levels of phosphocholine compared to nonmalignant breast tissue, and it appears likely that other unambiguous markers can be identified for many other pathologies if the signal to noise ratio (SNR) of the HR-MAS probe can be increased sufficiently. MAS is also utilized by thousands of NMR researchers in fields such as macromolecule structure determination, organo-metallo-complexes, and membrane proteins. HR NMR probes for liquids have become available with cryogenically cooled sample coils that are revolutionizing the field of NMR owing to their factor-of-four improvement in SNR. Greater improvements in SNR appear likely in HR-MAS. Our work thus far demonstrated a factor-of-three improvement in SNR in room temperature MAS experiments by cryogenically cooling the sample coil and tuning elements to 25 K while using a standard preamp with noise figure (NF) of 1.0. Another factor-of-two increase in SNR is expected by developing a cryogenically cooled low noise preamp with noise figure below 0.3 and other improvements. The rotating-frame field strength (B1) produced in the sample was severely limited by the poor high-voltage breakdown characteristics of capacitors used in the circuit. We present here, the basis for increasing the B1 field strength from 30 kHz to over 70 kHz on all channels by developing ultra-high Q ceramic disc capacitors that will handle peak voltages in excess of 3.5 kV. Substantial improvements in spinning at temperatures below 90 K will also be developed, which gives further gains in S/N in many systems and improved information on molecular dynamics.
Nuclear magnetic resonance (NMR) has been one of the most effective analytical tools for determining the structure of complex molecules in biology, chemistry, and medicine, but the NMR technique has had limited success for the very large molecules that are not soluble in suitable liquids. The instrument development proposed herein, called a CryoMAS NMR probe, if successful, will reduce the amount of time needed on very expensive NMR spectrometers by a factor of 30 to 100 (from months to days or hours) and thus make it practical to determine the structures of hundreds of thousands of biologically and chemically important macro-molecules for which structures are currently unknown. This is important to drug developments, catalysts, and enzymes, to name but a few.
