Jumping on the NMR Pulse Train

Nobody has the time or inclination to wait over a century for nuclear magnetic resonance (NMR) results. In the past, such a delay would understandably have hampered analysis of complex structures – but now, Kong Ooi Tan, a postdoctoral researcher at the Massachusetts Institute of Technology (MIT), and his colleagues have developed a novel way of improving the sensitivity of NMR spectroscopy to massively reduce the time needed to study the structures of intricate molecules (1). Using the new approach, scientists should be able to analyze complicated molecular structures, such as that of the amyloid beta (Aβ) protein linked to Alzheimer’s disease, in just one day – a fantastic improvement over the 110 years previous techniques would have required.

The polarization of an atom affects the sensitivity of NMR and can be increased to enhance sensitivity – for example, by using a stronger magnetic field. Dynamic nuclear polarization (DNP), an alternative technique developed by co-author Robert Griffin and colleague Richard Temkin (Associate Director of the Plasma Science and Fusion Center, MIT) over the past 25 years, boosts the polarization of NMR-active nuclei by transferring it from unpaired electrons of free radicals in the sample undergoing analysis. Traditional DNP can make NMR 100-fold more sensitive by continuously irradiating samples with high-frequency microwaves using a gyrotron. Unfortunately, it’s a power-hungry method that falls down at higher magnetic field strengths.

Using magic-angle spinning (MAS) NMR recoupling sequences as inspiration, Tan’s team decided to apply a train of microwave pulses separated by delays instead of continuously blasting the sample with microwaves. Carefully selecting the pulse length, power, and delay enhanced the polarization by a factor of up to 200 – similar to “traditional” DNP’s capabilities, but requiring only 7 percent of the power. Moreover, the new technique can be used at higher magnetic field strengths, offering further sensitivity enhancements. In their paper, the researchers emphasized that the efficiency of their sequence “is primarily determined by the timing of the pulses and delays rather than the microwave power.” Crucially, the timing can be controlled more reliably than the power, which can vary across a sample.

At the moment, the new technique has only been applied to standard test molecules in DNP juice (a glycerol/water mixture), but there are plans to study a range of low-abundance biological proteins, including Aβ, ion channels, and rhodopsin.