Diagnostic Devices Could Gain from Cutting NMR Spectroscopy Down to Size

Author: 
Bob Michaels

Scientists familiar with nuclear magnetic resonance (NMR) spectroscopy know that such systems have very large footprints, limiting their suitability for portable medical device applications. But thanks to the efforts of researchers at the University of California at Berkeley, a new method for performing zero-magnetic-field NMR spectroscopy could reduce the technology down to approximately the size of a shoebox. As a result, the technology could eventually find its way into patient-monitoring, imaging, and diagnostic devices.

Because NMR spectroscopy technology developed at UC Berkeley does not rely on large magnetic fields, it could eventually be incorporated into portable or handheld diagnostic devices.

“Traditional NMR spectroscopy relies on very large magnetic fields,” remarks Micah Ledbetter, an atomic physicist in UC Berkeley’s physics department. “The role of such magnetic fields is twofold: They create a high nuclear spin polarization so that a relatively large fraction of the nuclear spins are aligned with the magnetic field, and they also help to detect these nuclear spins.” However, for portable medical device applications, the problem with large-magnetic-field NMR spectroscopy systems is that they require large magnets.

The UC Berkeley NMR technology, in contrast, has replaced the requirement for a large magnetic field by generating a different kind of polarization using a technique known as parahydrogen-induced polarization. It also uses an atomic magnetometer to detect nuclear spins, eliminating the need for a very high precession frequency to determine the change in the orientation of rotating molecules in a sample. “Those are the two basic things that differentiate our technology from traditional NMR spectroscopy,” Ledbetter says. “Our system can actually detect nuclear spins in a zero magnetic field.”

Used in a range of applications, NMR spectroscopy analyzes and differentiates among molecules in a sample, according to Thomas Theis, a chemistry graduate student at UC Berkeley and one of Ledbetter’s collaborators. For example, in biochemical applications, it is traditionally employed to identify compounds and metabolites in the body. In conventional NMR, one of the most important signatures used for identifying a compound is that the same nuclei—protons in hydrogen, for instance—that are located at different sites on a molecule have different magnetic resonance frequencies, a phenomenon known as chemical shift. Instead of relying on chemical shifts to determine the molecular composition of a sample, the new technology relies on another feature of NMR spectroscopy: J-coupling.

This phenomenon, Ledbetter explains, is an interaction not between the nuclei and the magnetic field but between two different nuclei in a molecule. “The typical view of NMR is that nuclei spin around the magnetic field. Thus, you might think that in a zero-field system, there would be no signal,” he says. “But it turns out that you still have J-couplings, and they provide quite a lot of information about molecular structure.”

When people think of NMR in the medical device context, Ledbetter notes, MRI often comes to mind. MRI is based on NMR spectroscopy with the addition of certain kinds of gradients to encode spatial information, resulting in 2- and 3-D images of a subject. For example, parahydrogen-induced polarization is employed in high-field MRI to perform angiography, an imaging technique that maps the circulatory system. After a parahydrogen-polarized substance is injected into a vein, it can be detected using NMR spectroscopy. The Berkeley researchers’ results may enable clinicians to perform this type of imaging without having to use a large magnet.

“If one looks ahead, one might be able to apply what we’ve done to develop almost magnet-free imaging-type techniques,” Ledbetter adds. “People use high magnetic fields to do that now, but it’s possible that one could use our technology and do the same thing in a very low magnetic field, leading to the development of smaller MRI machines.

Devices for analyzing urine or blood samples are additional examples of portable or handheld diagnostic technologies that could eventually benefit from the UC Berkeley researchers’ zero-magnetic-field NMR system. “Currently performed in high-magnetic-field systems, such applications could possibly be reproduced in magnet-free devices,” Theis says. “However, perfecting such systems will require a lot of development.”