Weighing Device Achieves Zeptogram-Level Sensitivity

By Ernie Tretkoff

The most sensitive mass measurements so far have been made using a new nanomechanical device, opening the door to weighing single molecules one at a time. The tiny new scale can weigh molecules with zeptogram (10^-21g) sensitivity, reported Michael Roukes of Caltech and his colleagues at the APS March Meeting in Los Angeles.

The researchers have used the device to detect in real time a cluster of about 30 xenon atoms, which weighs 7zg, about the same as a single protein molecule. With further improvements, the device could be used to distinguish different biomarkers of cancer, and could lead to better, cheaper, and faster instruments for molecular identification and proteomics, said Roukes.

The device is a nanomechanical resonator, consisting of a tiny silicon carbide beam, about a micron long and about 100 nm wide. The beam is clamped at both ends, and set oscillating at over 100MHz.

To introduce the molecules or atoms to be weighed, the researchers open a shutter, allowing a brief spray of molecules–in this case a gas of xenon atoms or nitrogen molecules–to enter the chamber and condense onto the oscillating bar. The added mass lowers the beam’s resonant frequency by a precise amount, which the sensitive electronic circuitry detects, allowing the researchers to determine the weight of the added molecules. The device is currently sensitive to a few zeptograms.

Several years ago the Caltech research group achieved attogram (10^-18g) sensitivity with a similar, slightly larger, device made of silicon instead of silicon carbide. The new device works in essentially the same way as the previous version, but its smaller size and higher resonant frequency gives it a greater sensitively to added mass. The group hopes they can improve the design further to achieve sensitivity in the yoctogram (10^-24g) range–about the mass of a single hydrogen atom.

With the current zeptogram sensitivity the technique can detect a single protein molecule, but in order to distinguish between different proteins with similar masses, yoctogram-level sensitivity would be necessary, said Roukes. The goal of single biological molecule mass sensing is actually within reach, he said. "We believe we have the tools to do this."

The technology could eventually lead to the creation of microchips containing arrays of miniature mass spectrometers, which would be much cheaper and more convenient than the huge conventional mass spectrometers now in use in proteomics laboratories.

If they can improve the technology to achieve yoctogram sensitivity, the system could be used to detect the individual proteins secreted by cancer cells. "We hope to transform this chip-based technology into systems that are useful for picking out and identifying specific molecules one by one–for example, certain types of proteins secreted in the very early stages of cancer," said Roukes.