Magnet-free NMR: low-cost analysis on the horizon

NMR, free, at last

US researchers have demonstrated magnet-free nuclear magnetic resonance, opening up the possibility of low-cost, portable chemical analysis. Writing in the journal Nature Physics, the team says that it is just the beginning for the development of zero-field NMR although the team has already demonstrated that it is possible to get, clear, highly specific spectra.

Back in 2005, we reported in the original NMR Resonants column on SpectroscopyNOW how German researchers had found that the earth's magnetic field is strong enough to carry out NMR spectroscopy without an additional magnetic field. At the time, I suggested that the discovery might lead to a highly sensitive way to measure the magnetic fields around living creatures, sample the Earth's magnetic field, or test the composition of mineral oils in wells. Conventional NMR requires an homogeneous magnetic field of at least 1 Tesla if it is to be of high enough resolution to be useful in most analytical studies, such field strengths usually require expensive and immobile superconducting magnets. The Earth's magnetic field, by contrast, is 5 x 10^-5 T.

In the same, year, the team, which includes Bernhard Blümich of the Institute for Technical Chemistry and Macromolecular Chemistry in Aachen, Germany, and Alexander Pines of the US Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab), the University of California at Berkeley, and Carlos Meriles, a physicist at City College of New York, figured out how pulses of radio waves can compensate for the inhomogeneities in the magnetic fields of an NMR machine and so preclude the need for superconducting magnets in high-resolution spectroscopy.

Pining for the fields

Now, Pines' team working with Dmitry Budker of Berkeley Lab's Nuclear Science Division have finally eradicated external magnetic fields entirely. Readers will be well aware that conventional NMR requires a strong external magnetic field to be applied to align atomic nuclei because the net spin up, as opposed to spin down is just a few parts in a million. "Conventional wisdom holds that trying to do NMR in weak or zero magnetic fields is a bad idea," explains Budker, "because the polarization is tiny, and the ability to detect signals is proportional to the strength of the applied field." He adds that "Low- or zero-field NMR starts with three strikes against it: small polarization, low detection efficiency, and no chemical-shift signature," Budker says. However, getting rid of the large, expensive magnets would cut costs and make NMR and possibly its medical cousin magnetic resonance imaging (MRI) portable. "The hope is to be able to do chemical analyses in the field - underwater, down drill holes, up in balloons - and maybe even medical diagnoses, far from well-equipped medical centres," Budker team member Micah Ledbetter adds.

Hyperpolarisation can be used to increase net spin orientation by exploiting the differences between parahydrogen and orthohydrogen. There are also methods for boosting low-detection efficiency but by bringing the various techniques for addressing polarisation and inefficiency together it could be possible to address the missing chemical shifts in zero-field NMR too. Parahydrogen can be enhanced to 50% or even 100% at very low temperatures, although this requires the addition of a catalyst to reduce conversion times from days or weeks to something more reasonable. The net polarisation can then be transferred to a molecule of interest by hydrogenation. "With a high proportion of parahydrogen you get a terrific degree of polarization," explains Ledbetter. "The catch is, it's spin zero. It doesn't have a magnetic moment, so it doesn't give you a signal! But all is not lost."

This is where techniques for increasing detection efficiency are coupled to the polarisation process. In early low-field experiments, SQUID magnetometers were used but like the superconducting magnets, they inconveniently require cryogenic cooling to function. Optical-atomic magnetometers in contrast operate on a different principle in which an external magnetic field is measured by measuring the spin of the atoms inside the magnetometer's vapour cell, typically a thin gas of an alkali metal such as potassium or rubidium. Their spin is influenced by polarizing the atoms with laser light; if there's even a weak external field, they begin to precess. A second laser beam probes how much they are precessing and thus determines the external magnetic field strength; it's almost akin to NMR in reverse.

In the 2005 work, the Budker and Pines groups extended relaxation time and used optical-atomic magnetometry to image the flow of water using only the Earth's magnetic field or no field at all and to detect hyperpolarized xenon gas. In their current work they have managed to carry out a chemical analysis using zero-field NMR.

Sensitive sensors

"No matter how sensitive your detector or how polarized your samples, you can't detect chemical shifts in a zero field," Budker explains. "But there has always been another signal in NMR that can be used for chemical analysis - it's just that it is usually so weak compared to chemical shifts, it has been the poor relative in the NMR family. It's called J-coupling."

J-coupling was discovered in 1950 by NMR pioneer Erwin Hahn and his student, Donald Maxwell. It reveals how nuclear spins interact and how their associated electrons affect this interaction producing characteristic features in the spectrum that reveal bond angles and lengths. J-coupling is present regardless of whether an external magnetic field is present or not.

To demonstrate proof of principle, the team hydrogenated styrene with parahydrogen to form ethylbenzene. J-coupling determined with no external magnetic field using a specially built magnetometer, about the size of a football, revealed the position and orientation of the hydrogen atoms and the carbon-13 atoms to which they bond. They also measured J-coupling on a series of hydrocarbons derived from the hydrogenated styrene, including hexane and hexene, phenylpropene, and dimethyl maleate. These are all important starting materials for plastics, petrochemicals, perfumes and other products of the chemical industry.

Ledbetter's measurements produced signatures in the spectra which unmistakably identified chemical species and exactly where the polarized protons had been taken up. When styrene was hydrogenated to form ethylbenzene, for example, two atoms from a parahydrogen molecule bound to different atoms of carbon-13. J-coupling signatures are completely different for otherwise identical molecules in which carbon-13 atoms reside in different locations. All of this is seen directly in the results, says Budker. The team is already working to reduce the size of the magnetometer to make it even more portable.

It is still too early to say how well zero-field NMR might compete with the more conventional high-field NMR, but the development could ultimately herald the advent of a new approach to NMR that side-steps the ever-increasing demands for more powerful magnets with their ever-increasing costs.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.