Engineers at the Harvard School of Engineering and Applied Sciences (SEAS) have taken part in the development of a portable device for nuclear magnetic resonance (NMR) spectroscopy.
NMR spectroscopy disturbs protons within a molecule to ascertain important clues about its structure. It can 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, drug discovery, and industrial quality control.
Led by Donhee Ham, Gordon McKay Professor of Electrical Engineering and Applied Physics at SEAS, and his student Dongwan Ha, Ph.D., the team – including colleagues from the Schlumberger-Doll Research Center in Cambridge, Massachusetts, and the University of Texas, Austin – says it has shrunk the electronic spectrometer components, fitting them on a silicon chip smaller than a sesame seed. Combined with a compact permanent magnet, this spectrometer is said to represent the smallest device that can presently perform multidimensional NMR spectroscopy.
Significantly reducing the size and cost of the device – while also preserving the broad functionality of much larger spectroscopy setups – now enables the development of portable NMR spectrometers that could travel to remote sites for online, on-demand applications or to laboratories where larger systems would be prohibitively expensive. The chips can also operate accurately over a wide temperature range.
A paper demonstrating the use of this silicon-based chip with a compact permanent magnet will be published in Proceedings of the National Academy of Sciences (PNAS).
‘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,’ Ham said in a statement. ‘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.’
Permanent magnets are weaker than superconducting magnets but still adequate to resolve small-to-medium size hydrocarbons, drug compounds, and biomolecules such as metabolites and amino acids. The advent of these smaller magnets motivated Ham’s team to try to miniaturise the electronic components of the spectrometer. Those components include the transmitter and receiver for radio-frequency signals that coordinate complex proton motions and monitor the signifying responses that reveal the quantum-mechanical details of molecular structure.
In comparison to superconducting magnets, however, permanent magnets are far less stable. With slight changes in temperature, the magnetic field fluctuates and drifts – a challenge that accompanies the system miniaturisation. Ha, who is the main architect of the silicon spectrometer chip and lead author of the paper in PNAS, overcame the thermal problem.
‘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,’ Ham said. ‘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.’
While Ham and Ha demonstrated the tiny spectrometer chips for portable applications with the permanent magnet, they also see potential for a completely different application in conjunction with a larger superconducting magnet. The chips, they said, could one day be assembled into a massively parallel array in a superconducting magnet bore to accelerate analysis of complex molecules by performing many NMR spectroscopy experiments at once.
The research team has filed for a provisional patent on the miniature NMR spectrometer.