Fiscal Year:
2001
Title:
A 50 kHz MAS Probe for 1H High-Resolution NMR
Agency:
HHS
Contract:
N/A
Award Amount:
$128,356.00
Abstract:
DESCRIPTION: (provided by applicant) Available methods for molecular structure
determination, based primarily on x-ray crystallography and Nuclear Magnetic
Resonance (NMR) solution methods, have had very limited success on the
insoluble helical transmembrane proteins that are critical to biological
function. Various techniques are under development to enhance the effectiveness
of solids NMR, where high-speed Magic Angle sample Spinning (MAS) has been most
fruitful for low-gamma nuclides. To date, MAS has not been effectively applied
to proton (1H) NMR of macromolecules for a combination of instrumentation
reasons that will be systematically addressed in the proposed research.
Preliminary simulations using advanced Computational Fluid Dynamics (CFD)
software show that a combination of (1) novel supersonic microturbine blade
designs, (2) novel supersonic surface cooling techniques, and (3) advanced
silicon-nitride micro-machining techniques offers the potential for a factor of
4 increase in practical spinning speed (from 12 kHz to 50 kHz) for proton NMR
on temperature-sensitive, dilute, biological systems. Experiments have
confirmed that pressurized rf sample coils offer the potential for a factor of
four increase in i-f pulse power handling and thus improved performance of
advanced line-narrowing techniques such as frequency-switched and
phase-modulated Lee-Goldberg homonuclear decoupling. This Phase I project will
demonstrate feasibility of supersonic surface speeds in MAS rotors with a
factor of five reduction in frictional heating in both a 4 mm and a 2 mm sample
rotor at 7 T. Phase II will complete the developments necessary for 1H
inverse-detection in triple-resonance MAS with pulsed-field gradient at fields
up to 18.8 1 (800 MHz) in narrow-bore magnets. Initial field testing at an
outside institution is expected by the end of the first year in Phase II.
PROPOSED COMMERCIAL APPLICATION:
There are more than 3,000 high-field NMR systems installed world-wide, and annual NMR
equipment sales are currently approximately $300M. There is strong medical and scientific
interest in determining the structures of approximately 20,000 membrane proteins over the
10-15 years, though suitable methods are currently not available. The proposed MAS
probe development could enable thousands of NMR researchers to contribute to this effort
at the relatively modest system upgrade cost of $35,000-$50,000, depending on field and
interests. Total upgrade market potential over the decade following completion of the
Phase II exceeds $40M.
Principal Investigator:
F. D. Doty
Small Business Information at Submission:
DOTY SCIENTIFIC, INC.
700 CLEMSON RD COLUMBIA, SC 29229
EIN/Tax ID:
570736944
DUNS:
N/A
Number of Employees:
N/A
Woman-Owned:
No
Minority-Owned:
No
HUBZone-Owned:
No