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 report the development of a radically different approach to NMR. The 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.
"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 research team reports the work in the online and print editions of the Proceedings of the National Academy of Sciences the week of May 14. Lead author Yael Maguire, a former MIT graduate student who earned his Ph.D. for this work, will give a talk on it May 16 at the VII European Protein Symposium in Stockholm.
NMR, along with X-ray crystallography, is commonly used to determine the structure of proteins and other molecules. NMR probes normally consist of a coil that surrounds the sample being studied. The coil creates a magnetic field that interacts with the nuclear spin of atoms in the sample, and those interactions reveal how the atoms are connected.
Instead, research originally aimed at improving quantum computing led the MIT researchers to a completely different approach based on guiding waves.
"We were trying to get away from coils and see if we could find a new way to look at it," said Maguire, now a visiting researcher at MIT and chief technology officer of Cambridge-based ThingMagic.
How it works
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 Cruetzfeld-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.
Asking big questions
Maguire got the idea for the project after talking to Zhang and asking him what kind of new device would make the biggest impact in biology. For Zhang, the answer was immediate: improving NMR.
Elucidating structure is critically important for biologists because structure determines function, said Zhang. The goal for the project was to create an NMR detector sensitive enough to detect structural information using the amount of protein in a spot on a two-dimensional gel used for electrophoresis (about 1014 molecules).
The task was daunting. "Nobody in their right mind would try to take one spot from that gel and get a molecular structure from it," said Zhang.
However, Zhang said that he believes in the sentiment expressed by Francis Crick, the legendary biologist who determined the double helix structure of DNA along with James Watson: You need to ask big questions in order to get big answers.
Zhang adds that the project probably never would have happened without interdisciplinary collaboration: "Biologists would never have thought of this type of machine, but a physicist would never have asked the question," he said.Before starting this project, Maguire and Gershenfeld, with co-author Isaac Chuang, had already used NMR to create early quantum computers.
Their effort to improve the computing capabilities turned out to be surprisingly relevant to detecting molecular structures, an "unexpected spinoff," said Gershenfeld."We were not at all thinking about biology, but this turned out to be exactly what was needed to improve biological sensitivity,"
The research was funded by the National Science Foundation.
Anne Trafton | MIT News Office
Wireless power can drive tiny electronic devices in the GI tract
28.04.2017 | Brigham and Women's Hospital
Artificial intelligence may help diagnose tuberculosis in remote areas
25.04.2017 | Radiological Society of North America
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences