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 HRNMR to extend the technique to inhomogeneous systems, such as human and animal tissues. The 1H HRMAS 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 recently become available with cryogenically cooled sample coils that are revolutionizing the field of NMR owing to their factor-of-four improvement in SNR. Similar improvements in SNR may be possible in HR-MAS. The engineering challenges of developing a cryo-coil HR-MAS probe are enormous, but not insurmountable. Detailed circuit analysis, full-wave electromagnetic coil analysis, computational fluid dynamics (CFD), thermal simulations, and MAS experiments show that a combination of (1) a novel approach to quad-resonance MAS (IH/13C/2H/15N) with all of the critical circuit elements maintained near 25K, (2) integrating a ceramic dewar into a novel sample spinner system, and (3) cryogenic preamps offers the potential for a factor-of-four increase in SNR in a cryo-coil HR-MAS probe at fields at least up to 14T (600 MHz). The Phase I has demonstrated technical feasibility of a bewared MAS spinner design with a high-efficiency quad-resonance cryogenic circuit for more than an order-of-magnitude reduction in signal acquisition time. Phase II will complete the developments necessary for quad-resonance cryo-coil HR-MAS with pulsed-field gradients at fields up to 14T. Initial field-testing at the University of Georgia is expected midway through the Phase II. Subsequent work following this Phase II is expected to extend the technology to 800 MHz.
