MIT researchers have developed a way to dramatically enhance the sensitivity of nuclear magnetic resonance spectroscopy (NMR), a technique used to study the structure and composition of many kinds of molecules, including proteins linked to Alzheimer's and other diseases.
Using this new method, scientists should be able to analyze in mere minutes structures that would previously have taken years to decipher, says Robert Griffin, the Arthur Amos Noyes Professor of Chemistry. The new approach, which relies on short pulses of microwave power, could allow researchers to determine structures for many complex proteins that have been difficult to study until now.
"This technique should open extensive new areas of chemical, biological, materials, and medical science which are presently inaccessible," says Griffin, the senior author of the study.
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MIT postdoc Kong Ooi Tan is the lead author of the paper, which appears in Sciences Advances on Jan. 18. Former MIT postdocs Chen Yang and Guinevere Mathies, and Ralph Weber of Bruker BioSpin Corporation, are also authors of the paper.
Enhanced sensitivity
Traditional NMR uses the magnetic properties of atomic nuclei to reveal the structures of the molecules containing those nuclei. By using a strong magnetic field that interacts with the nuclear spins of hydrogen and other isotopically labelled atoms such as carbon or nitrogen, NMR measures a trait known as chemical shift for these nuclei. Those shifts are unique for each atom and thus serve as fingerprints, which can be further exploited to reveal how those atoms are connected.
The sensitivity of NMR depends on the atoms' polarization -- a measurement of the difference between the population of "up" and "down" nuclear spins in each spin ensemble. The greater the polarization, the greater sensitivity that can be achieved. Typically, researchers try to increase the polarization of their samples by applying a stronger magnetic field, up to 35 tesla.
Another approach, which Griffin and Richard Temkin of MIT's Plasma Science and Fusion Center have been developing over the past 25 years, further enhances the polarization using a technique called dynamic nuclear polarization (DNP). This technique involves transferring polarization from the unpaired electrons of free radicals to hydrogen, carbon, nitrogen, or phosphorus nuclei in the sample being studied. This increases the polarization and makes it easier to discover the molecule's structural features.
