13:15 08 July 2008
The revolutionary scanner is many times smaller than conventional NMR spectroscopy machines, which require huge magnets to create the powerful magnetic fields necessary to make them work.
Nuclear magnetic resonance spectroscopy works by lining up nuclei in a sample using a powerful magnetic field and then zapping them with radio waves that cause them to wobble, or precess.
This precession induces currents in a nearby coil which can be used to determine the chemical structure of the molecules that contain the nuclei. The same process is used in magnetic resonance imaging machines to make non-invasive images of human bodies. The new device does not produce images, however.
In conventional NMR spectroscopy machines, powerful fields are necessary to line up individual nuclei.
However, Ralph Weissleder at Harvard Medical School in Cambridge, Massachusetts, US, and colleagues have found that magnetic nanoparticles generate a much larger signal than single nuclei, and can thus be detected using the weaker fields from small permanent magnets.
The trick that Weissleder and colleagues have perfected is to coat these nanoparticles with molecules that bind to specific biomolecules, or bacteria and viruses.
This binding process causes the nanoparticles to clump together, producing a measurable change in the signal they produce. In this way, the team says it can identify a large variety of biological targets.
The team has squeezed the electronics that detect and interpret the signals onto a chip just 2 millimetres square (pdf format).
Small and sensitive
What's more, the researchers have also designed a microfluidics network that shuttles the samples around and concentrates them in volumes of just five millionths of a litre (5 microlitres) – some 60 times less than conventional systems.
"The smaller the system, the better the sensitivity in terms of absolute amount of sample that can be detected," says Hakho Lee, lead author on the research.
The prototype device has eight tiny coils, each of which can monitor nanoparticles sensitive to different biomolecules. Future devices could employ many more such coils.
The result is a prototype machine that is 800 times more sensitive than standard NMR scanners used in many laboratories, says Weissleder.
The team put the prototype through its paces, showing that it is sensitive enough to detect just 10 bacteria in a given sample. By loading each of the eight microcoils with different nanoparticles, the system could distinguish between simulated blood samples representing healthy individuals, those with cancer, and those with diabetes, by looking for eight different biomarker molecules.
"The biggest advantage is that we don't need sample preparation or purification steps," Lee says. The nanoparticles are simply added to whatever samples are present. "This method could provide an easy and fast way to diagnose almost any kind of disease, such as bacterial infection or cancers in point-of-care settings – right next to the patient or in developing countries."
The device could also be used to test for water purity or even applied to gaseous samples, to search for airborne pathogens or pollutants.
Other researchers are impressed with the work. "If you came to my lab you would see that our spectrometers occupy whole rooms, and we are always struggling with sensitivity in NMR experiments," says Dusan Uhrin, an NMR spectroscopist at the University of Edinburgh.
"They have been able to improve the sensitivity such that they can detect just a few bacteria. It's quite remarkable that they can detect down to that limit," he says.
Weissleder has filed a patent for the design and started a company called T2 Biosystems to market the devices.
Journal reference: Nature Medicine (DOI: 10.1038/nm.1711)T2 Biosystems
United States Patent Application 20060269965