Like a minuscule bathroom scale, a tiny vibrating gizmo can weigh individual molecules, a team of physicists reports. The new device could open up new realms of mass spectroscopy, the science of measuring molecules' masses to help identify them. However, opinions vary on the ultimate utility of the technique.
"How applicable this will be to generalized mass spectroscopy, time will tell," says John Kasianowicz, a biophysicist at the National Institute of Standards and Technology in Gaithersburg, Maryland, who was not involved with the new study. "But I think this is a major advance."
Traditional mass spectroscopy uses a magnetic field to bend the path of electrically charged molecules. How much their path is bent reveals their mass. But this technique isn’t ideal for jumbo biomolecules that weigh roughly a million times as much as a proton. These hefty molecules move so slowly, for example, that they don't trigger the conventional particle detectors that sit on the other side of the magnetic field.
So scientists are exploring alternatives. For more than a decade, Michael Roukes and his team at the California Institute of Technology (Caltech) in Pasadena have been experimenting with tiny vibrating beams that they carve out of materials such as silicon. Weighing about a trillionth of a gram, such a beam generally spans a gap, like a bridge suspended over a valley, and can be made to vibrate from side to side at millions of cycles per second.
In principle, such a device can measure the mass of a molecule: When a molecule sticks to such a beam (through a process called physisorption), the added mass causes the beam to vibrate at a lower frequency. So to measure the molecule's mass, researchers need only measure that frequency shift.
There is a hitch, however. The frequency shift also depends on where on the beam the molecule lands, so that a lighter molecule landing in the middle of the beam could produce the same frequency shift as a heavier molecule landing closer to one end.
Now, Roukes, his postdoc Mehmet Selim Hanay, and colleagues at Caltech and the French Atomic Energy Commission in Grenoble have found a way around that ambiguity. The key is to shake the bridge simultaneously at two different frequencies, the researchers report this month in Nature Nanotechnology.
Like a guitar string, a bridge can vibrate in distinct patterns of motion, or modes, each of which has its own distinct frequency. In the lowest frequency mode, the whole beam bows side to side. (See figure, upper right inset.) In the next higher-frequency mode, the two halves of the bridge bow in opposite directions while the point in the center remains stationary. (See figure, lower left inset.) In fact, the beam can vibrate in both of these modes at once. When a molecule sticks to the bridge, it will lower the frequency of both modes by different amounts. From those two frequency shifts, the scientists can deduce both the molecule's position on the beam and its mass.
To prove it, they measured the masses of gold nanoparticles as they latched onto a vibrating silicon beam. In a second proof-of-principle demonstration, they measured the masses of molecules of the antibody human immunoglobulin M landing on a similar bridge 10 micrometers long, 300 nanometers wide, and 160 nanometers thick. The molecules generally clump together to form multiunit complexes, and the researchers resolved the number of units in each complex.
There aren't a lot of other techniques that can measure individual molecules, Kasianowicz says. For example, he and colleagues have developed a method in which individual molecules get stuck in nanometer-sized pores. But compared with his own method, the vibrating beam may have more applications, he says, especially if many beams can be put on a single chip. "This has the opportunity to be the Gillette razor of mass spectroscopy," he says. "You use a chip three or four times and then throw it away."
Roukes thinks the vibrating-beam technique can even go toe-to-toe with traditional mass spectrometry, which after a century of work has become a high art. For example, he envisions using an array of the sensors to identify every protein in human blood serum, the so-called plasma proteome.
That suggestion raises some eyebrows. "We do a lot of plasma proteome work and that [idea] is really stretching it," says John McLean, an analytic chemist at Vanderbilt University in Nashville. Roukes's technique measures only mass and doesn’t chemically identify any molecule, McLean says, so it may not be helpful in sorting out the mishmash in the plasma proteome.
Still, McLean says, the new technique seems ideal for studying molecules with mass between 1 million and 10 million times that of the proton, a range too heavy for traditional mass spectroscopy and too light for other techniques such as electron microscopy: "I think there's a really good niche for it in this no-man's land of mass."