Caltech-led team creates device to weigh molecules


Scientists have created a tiny measuring scale 300 times smaller than the width of a human hair that can weigh a single molecule at a time. The device may one day help doctors diagnose disease and illuminate the complex inner machinery of cells, its makers say.

An international team led by Caltech researchers built the device to measure the mass of large molecules that are difficult to analyze through conventional mass spectrometry methods. The scale features a long, bridge-like structure that vibrates at a specific frequency. When molecules are fired at the bridge in succession, they alter the frequency according to their weight.

“Think of it as a violin or a guitar string,” senior author Michael Roukes said of the bridge-like resonator. “If you put a little blob of solder on it, the weight would make the frequency change, ever so slightly.... That’s what we’re measuring.”


Roukes, an experimental physicist, explained that electrostatic forces are used to “strum” the resonator as molecules are flung at it. The resulting dips in the frequency are recorded in hertz, or vibrations per second, on a computer.

The scientists described their invention in last Sunday’s issue of the journal Nature Nanotechnology and showed it could accurately weigh immunoglobulin M — an antibody produced by immune cells in the blood — and 5-nanometer gold particles. (A nanometer is one-billionth of a meter in length.)

The device, called a nanomechanical system (NEMS) resonator, fills a gap in what Roukes calls a no man’s land in molecular measurement. The accuracy of conventional mass spectrometry begins to fade with larger, albeit still tiny, objects. The NEMS resonator can weigh those heftier items, which include proteins, air pollution particles and viruses with masses more than 500 kilodaltons — equivalent to half a million hydrogen atoms.

“There is certainly research that could be better addressed if we could get better measurements in that range,” said Allis Chien, director of Stanford University’s mass spectrometry laboratory, who was not involved in the study. “On the surface, it certainly sounds great, but I’d like to find out how accurate those measurements are. A lot depends on how much material you need and how difficult it is to prepare samples for it.”

The device, co-developed with researchers in France and India, represents roughly 12 years of research and is still being refined. Roukes estimated that within five years the system would be able to weigh extremely light objects in addition to heavier ones.

“When that happens, we think that this will supplant existing techniques for doing mass spectrometry,” he said.


The researchers expect that the device will be most useful in the study of protein molecules, the workhorses of living cells. It could help analyze the vast array of proteins within a human — the so-called proteome. And since the line-up of proteins in a cell reflects its health, the device may one day be used as a diagnostic tool.

“If you want to get an instantaneous snapshot of what your physiological state is, your proteome tells you that,” Roukes said. “This technology is perhaps the first to offer a realistic prospect of being able to do a personalized proteome in a reasonable period of time.”

Such analysis would require hundreds — or tens of thousands — of scales working in parallel. Roukes said that because the device is constructed of silicon, it can be mass-produced the way computer chips are.