Experts design portable NMR spectrometer

A team of engineers at the Harvard School of Engineering and Applied Sciences (HSEAS), alongside collaborators from the University of Texas, have created a two-by-two millimetre spectrometer designed for the multidimensional analysis of molecules.

A paper demonstrating the use of this technology has been published in the journal Proceedings of the National Academy of Sciences.

NMR spectroscopy is designed to unsettle protons within a molecule to help gain important information about its structure.

“One year of testing could be completed in a few days. We have already started investigating this angle

Lead engineer Donhee Ham

Its application in research can help identify unknown substances detect very slight variations in chemical composition, and measure how molecules interact, making it an essential tool in organic chemistry, structural biology, and drug discovery, as well as for quality control in many industries, the HSEAS said.

Engineers, led by HSEAS professor Donhee Ham, have developed techniques to dramatically reduce the size of the electronic spectrometer components, fitting them on a silicon chip smaller than a sesame seed.

Used in combination with a compact permanent magnet, the HSEAS team says this minuscule spectrometer represents the smallest device that can presently perform multidimensional NMR spectroscopy.

Having reduced the overall size and cost of such a device, Ham and his team has suggested it could be used at remote sites for online, on-demand applications or simply to laboratories where large, state-of-the-art systems would be prohibitively expensive.

“State-of-the-art NMR systems use very large superconducting magnets, and they are indeed necessary for probing the structure of complex molecules like proteins,” said Ham.

“But in many circumstances – for example, many experiments in biochemistry or organic chemistry, quality control in production lines, or chemical reaction monitoring – you’re doing NMR on smaller molecules, and for those applications the big superconducting magnets may be avoided.”

Utilising permanent magnets which have been dramatically reduced in size, Ham’s team set about miniaturising the electronic components of a spectrometer.

According to an HSEAS statement, those components include the transmitter and receiver for radio-frequency signals that orchestrate complex proton motions and monitor the ’tell-tale’ responses that reveal the quantum-mechanical details of molecular structure.

However, one of the key issues associated with using smaller permanent magnets, as opposed to superconducting magnets, is their stability - as their magnetic fields tend to fluctuate and drift.

Ham’s research student Dongwan Ha, however, was able to overcome this issue.

“Not only did Dongwan design the chip, but he also came up with a way to use statistical distance minimisation and entropy minimisation to estimate the magnetic field drift and calibrate out its effect,” explained Ham.

“This signal-processing method obviates the need for physical thermal regulation for the permanent magnet, which would have added hardware and increased the power consumption. That would have defeated our aim of achieving portability.”

Expanding the research, Ham suggests the silicon chips could potentially be assembled into a massively parallel array in a superconducting magnet bore to tremendously accelerate analysis of complex molecules by performing many NMR spectroscopy experiments at once.

“An individual NMR spectroscopy experiment is inherently slow, taking several minutes to hours,” said Ham.

“Using a hundred of these cheap and small spectrometer chips in parallel within a superconducting magnet bore could counter the intrinsic slowness of NMR spectroscopy, enabling a high-throughput paradigm for pharmaceutical screening and structural biology.

“One year of testing could be completed in a few days. We have already started investigating this angle.”