Detecting the molecular structure of a tiny protein using nuclear magnetic resonance (NMR) currently requires two things: a million-dollar machine the size of a massive SUV, and a large sample of the protein under study.
Now, researchers from MIT‘s Center for Bits and Atoms have developed a radically different approach to NMR. Their new highly sensitive technique, which makes use of a microscopic detector, decreases by several orders of magnitude the amount of protein needed to measure molecular structure.
The new technology could ultimately lead to the proliferation of tabletop NMR devices in every research laboratory and medical office. Among other things, such devices could prove invaluable in diagnosing a variety of diseases.
The research team, led by Yael Maguire, reported their work in the online and print editions of the Proceedings of the National Academy of Sciences.
‘It’s revolutionary,’ said Shuguang Zhang, one of the authors and associate director of MIT’s Center for Biological Engineering. ‘It’s not just incremental progress.’
The new approach starts with technology similar to the Wi-Fi antennas found in laptop computers. These antennas consist of a flat strip of metal. Using a laser, the MIT team made a microscopic defect (a slot) in such a conducting structure, known as a strip line. In that location a little bit of the magnetic field leaks out of the line, creating a uniform, concentrated magnetic field. That field allows the slot to be used as an NMR probe, in place of a coil.
The detector described in the PNAS paper is a plastic card about one-third the size of a credit card and is easy and inexpensive to produce. To get structural information, the new detector must still be placed in a massive machine housing a superconducting magnet, just as the coil probes are. However, the MIT researchers anticipate that the microslot’s small sample volume will allow much smaller tabletop spectrometers to be developed.
Zhang said such NMR devices could prove especially valuable in diagnosing diseases caused by misfolded proteins, such as Alzheimer’s and Huntington’s, or prion diseases like Creutzfeld-Jakob disease. It could also allow early detection of glaucoma and cataracts, which could be diagnosed by testing a single teardrop. ‘You could detect it so early it will become treatable,’ Zhang said.
The new technology could dramatically improve the rate of biomedical research, because it can take up to a year to obtain enough material for an NMR study using the coil probes, said co-author Professor Neil Gershenfeld, director of MIT’s Center for Bits and Atoms. That is ‘a major limiting step in drug discovery and studying biological pathways,’ he said.
The probes could also be used to make portable devices for diagnostics or soil analysis. And because the smaller devices are cheaper to make, they should be affordable even in developing countries where NMR machines are now rare, said Zhang.
The research was funded by the National Science Foundation.