Nuclear magnetic resonance (NMR), a scientific technique associated with outsized, very low-temperature, superconducting magnets, is one of the principal tools in the chemist’s arsenal, used to study everything from alcohols to proteins to such frontiers as quantum computing. In hospitals the machinery of NMR’s cousin, magnetic resonance imaging (MRI), is as loud as it is big, but nevertheless a mainstay of diagnosis for a wide range of medical conditions.

It sounds like magic, but now two groups of scientists at Berkeley Lab and UC Berkeley, one expert in chemistry and the other in atomic physics, long working together as a multidisciplinary team, have shown that chemical analysis with NMR is practical without using any magnets at all.

Dmitry Budker of Berkeley Lab’s Nuclear Science Division, a professor of physics at UC Berkeley, is a protean experimenter who leads a group with interests ranging as far afield as tests of the fundamental theorems of quantum mechanics, biomagnetism in plants, and violations of basic symmetry relations in atomic nuclei.

Alex Pines, of the Lab’s Materials Sciences Division and UCB’s Department of Chemistry, is a modern master of NMR and MRI. He guides the work of a talented, ever-changing cadre of postdocs and grad students known as the “Pinenuts” – not only in doing basic research in NMR but in increasing its practical applications. Together the groups have extended the reach of NMR by eliminating the use of magnetic fields at different stages of NMR measurements, and have finally done away with external magnetic fields entirely.

Spinning the information

NMR and MRI depend on the fact that many atomic nuclei possess spin (not classical rotation but a quantum number) and – like miniature planet Earths with north and south magnetic poles – have their own dipolar magnetic fields. In conventional NMR these nuclei are lined up by a strong external magnetic field, then knocked off axis by a burst of radio waves. The rate at which each kind of nucleus then “wobbles” (precesses) is unique and identifies the element; for example a hydrogen-1 nucleus, a lone proton, precesses four times faster than a carbon-13 nucleus having six protons and seven neutrons.

Spectroscopy with conventional nuclear magnetic resonance (NMR) requires large, expensive, superconducting magnets cooled by liquid helium, like the one in the background. The Pines and Budker groups have demonstrated NMR spectroscopy with a device only a few centimeters high, using no magnets at all (foreground). A chemical sample in the test tube (green) is polarized by introducing hydrogen gas in the parahydrogen form. The sample’s NMR is measured with an optical-atomic magnetometer, at center; laser beams crossing at right angles pump and probe the atoms in the microfabricated vapor cell. (Click on image for best resolution.)

Being able to detect these signals depends first of all on being able to detect net spin; if the sample were to have as many spin-up nuclei as spin-down nuclei it would have zero polarization, and signals would cancel. But since the spin-up orientation requires slightly less energy, a population of atomic nuclei usually has a slight excess of spin ups, if only by a few score in a million.

“Conventional wisdom holds that trying to do NMR in weak or zero magnetic fields is a bad idea,” says Budker, “because the polarization is tiny, and the ability to detect signals is proportional to the strength of the applied field.”

The lines in a typical NMR spectrum reveal more than just different elements. Electrons near precessing nuclei alter their precession frequencies and cause a “chemical shift” — moving the signal or splitting it into separate lines in the NMR spectrum. This is the principal goal of conventional NMR, because chemical shifts point to particular chemical species; for example, even when two hydrocarbons contain the same number of hydrogen, carbon, or other atoms, their signatures differ markedly according to how the atoms are arranged. But without a strong magnetic field, chemical shifts are insignificant.

A molecule of parahydrogen hydrogenates a styrene molecule to form ethylbenzene. J-coupling reveals the position and orientation of the hydrogen atoms and the carbon-13 atoms to which they bond. The upper panel shows a simulated spectrum, in blue, of coupling between a hydrogen and a carbon in the methyl position. The actual experimental data are in white. The lower panel shows simulation of coupling in the methylene position, in green, with actual data in white. Simulation and experiment are in close agreement, indicating the promise of the zero-field technique for chemical fingerprinting.

“Low- or zero-field NMR starts with three strikes against it: small polarization, low detection efficiency, and no chemical-shift signature,” Budker says.

“So why do it?” asks Micah Ledbetter of Budker’s group. It’s a rhetorical question. “The main thing is getting rid of the big, expensive magnets needed for conventional NMR. If you can do that, you can make NMR portable and reduce the costs, including the operating costs. 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 centers.”