Nuclear magnetic resonance (NMR) spectroscopy could be about to go mobile, thanks to a team of researchers in the US that has shrunk the electronic components needed for the spectroscopic technique down to fit on an integrated circuit the size of a grain of sand. The team’s chip, combined with compact, state-of-the-art magnets, could lead to portable devices that can help identify chemicals in lab reactions and on industrial production lines.
NMR spectroscopy, a technology that has helped visualize the chemical structures of countless compounds, allows scientists to gather information from the spins – the inherent magnetic moments – of atomic nuclei. When compounds with certain nuclei, like those of hydrogen or the isotope carbon-13, are placed in a strong magnetic field, the nuclear spins align with or against the magnetic field. If the nuclei are then bombarded with electromagnetic radiation at a frequency determined by the magnetic-field strength, the directions of the nuclear spins will precess. It is then possible to measure the precession frequencies of the spins of nuclei in a sample to determine how a molecule’s atoms are arranged.
While scientists have used NMR spectroscopy since the 1950s, the necessary hardware has typically been bulky, requiring superconducting magnets larger than a person and electronics the size of a kitchen cabinet. Recently, smaller permanent magnets that are good enough for NMR have come on to the market and some of the electronic components have been integrated onto semiconductor chips, which has enabled table-top systems that can probe small molecules. But a miniaturized integrated system with a full range of NMR spectroscopy capabilities had not been developed.
Now, though, a team based at Harvard University has done just that. The researchers placed a radio-frequency (RF) transmitter and receiver along with a component known as an “arbitrary pulse sequencer” onto a silicon chip with a surface area of 4 mm2. The scientists then combined their chip with a cube-shaped magnet around the size of a large grapefruit and were able to analyse a variety of compounds. To do the analyses, samples are placed inside a small hole in the centre of the magnet.
The key advance was miniaturizing and integrating the pulse sequencer, which controls the timing, shapes and amplitudes of the RF pulses directed at the sample being measured, says Donhee Ham, the Harvard physicist who led the research. “The arbitrary pulse sequencer is the brain of the entire chip,” he says.
The electronics the team developed are an improvement on those of previous portable systems, which have so far only implemented simplified NMR techniques that cannot fully resolve complex molecular structures, says Ham. The more sophisticated technique of “multidimensional” NMR spectroscopy can be extremely useful when trying to probe structures beyond the most basic molecules. With the new integrated pulse sequencer, the researchers can “control the RF transmitter in any way we desire, so the transmitter can produce any RF pulse sequence”, according to Ham – a requirement for multidimensional NMR spectroscopy.
In addition to enabling portable spectroscopy, the team’s miniaturized electronics could be coupled with larger magnets to greatly speed up the NMR process. By incorporating dozens of the chips into a large superconducting magnet, researchers could scan many samples at once rather than one at a time, which can be a laborious process. Such a “high throughput” spectroscopy scheme could accelerate drug discovery, Ham says.
The team’s work “represents a further step towards the complete miniaturization of an NMR spectrometer”, says Giovanni Boero of the Swiss Federal Institute of Technology in Lausanne. But Boero says that the integration of the pulse sequencer is a technical advance rather than a game changer. “It is not a revolutionary paper, but it is an important work in the frame of the worldwide effort towards the goal of performing NMR spectroscopy using a low-cost, highly portable system.”
The work is published in the Proceedings of the National Academy of Sciences.