A way to acquire chemical information with magnetic fields a million times weaker than those used in typical nuclear magnetic resonance (NMR) spectroscopy has been developed by a team led by John Clarke and Alexander Pines. Clarke is a professor of physics and Pines a professor of chemistry at UC Berkeley, and both are members of Berkeley Lab's Materials Sciences Division.

NMR and its near relative, magnetic resonance imaging (MRI), are essential tools of scientific research and medical diagnosis. Yet NMR is often limited to samples that can be placed inside the bore of a big, high-field magnet. Because very strong magnetic fields of a tesla or more (a tesla is some 20,000 times the Earth's magnetic field strength) must be exquisitely adjusted to reduce variations in intensity, NMR apparatus is expensive and cumbersome.

The secret of low-field success, says Robert McDermott, a graduate student in Clarke's laboratory and an author of a recent paper in Science describing the method, is to use a superconducting quantum interference device, or SQUID, the most sensitive magnetic field detector ever devised, along with a technique called prepolarization that aligns spinning nuclei.

Pushing the state of the art

SQUIDs have been used in NMR measurements since the 1980s, but mostly for solid samples at extremely low temperatures. To analyze liquids at room temperature, the Clarke-Pines team heated their samples in an insulated chamber surrounded by the SQUID's pick-up coils. The SQUID itself — a tiny loop of superconductor interrupted at two points by weak links, called Josephson junctions — operated in a bath of liquid helium.

A superconducting quantum interference device, or SQUID, is a tiny loop of superconducting material interrupted by narrow gaps called Josephson junctions.

Other recent SQUID experiments done at room temperature have employed magnetic fields of several thousandths of a tesla (milliteslas). The Clarke-Pines team's measurement field was less than two millionths of a tesla (microteslas), a small fraction of the Earth's magnetic field strength.

All NMR depends on the fact that some kinds of spinning nuclei generate their own magnetic fields. These can be lined up by an external magnetic field, then knocked off axis by a burst of radio waves. The rate at which each kind "wobbles" (precesses) is unique; for example, a hydrogen nucleus precesses four times faster than a carbon-13 nucleus. A detector can pinpoint the type of element by tuning to its precession frequency, known as the Larmor frequency.

Lines in an NMR spectrum reveal more than just different elements. Nearby electrons can alter precession frequency, causing a "chemical shift" — moving the signal or splitting it into separate lines in an NMR spectrum. Chemical shifts point to particular compounds, as in the arrangement of hydrogen and carbon atoms in alcohols.

"Chemical shift grows linearly with field strength," says Andreas Trabesinger, a postgraduate fellow in the Pines laboratory and another of the Science paper's authors, explaining another reason why NMR uses strong magnets. "The higher the field, the higher the Larmor frequency, and the stronger the signal."

Detectors tuned to Larmor frequencies are not the only way to distinguish nuclear magnetic signals. Such detectors report the frequency of change in magnetic flux (the number of magnetic field lines through a surface), while SQUIDs can detect magnetic flux directly, sensing the magnetic field generated by even a slowly precessing nucleus. The resulting signal is weak but extremely sharp: the lower the magnetic field, the narrower the NMR line, yielding a signal-to-noise ratio far superior to that of high-field NMR.

"SQUIDs are frequency-independent," says McDermott. "To achieve low-field NMR, we realized we could play this trick of operating with an untuned detector."

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