California Institute of Technology (Caltech) scientists managed to create the first mass spectrometer at the nanoscale in the world. The device is able to measure the mass of single molecules in real-time, combining the action of components several billionths of a millimeter in size. The new method is a significant break-off from the traditionally complex process of large-scale mass spectrometry, which is incredibly  cumbersome to perform. Details of the accomplishment appear in the latest issue of the journal Nature Nanotechnology.

In regular mass spectrometry, samples containing several tens of hundreds of molecules are ionized, a process that results in electrically charged atoms called ions. These components are then directed into an electrical field, where the way they move around is analyzed. The movement patterns are generated by their masses and energies, which allows physicists to extract their mass-to-charge ratio. Ultimately, this knowledge can be used to obtain the actual mass of the targeted molecules.

In the new nanoscale method devised at Caltech, this cumbersome procedure is significantly simplified. The spectrometer is basically made up of two nanoelectromechanical system (NEMS) resonators, tiny, bridge-like structures, two micrometers long and 100 nanometers wide. These resonators vibrate energetically against each other, essentially creating a “scale” on which the mass of the molecule is measured.

“The frequency at which the resonator vibrates is directly proportional to its mass. When a protein lands on the resonator, it causes a decrease in the frequency at which the resonator vibrates and the frequency shift is proportional to the mass of the protein,” Askshay Naik, the first author of the journal paper, and a research physicist at the institute, explains the basic operating mechanism. The entire work was made possible through the decade-long efforts of Caltech Professor of Physics, Applied Physics, and Bioengineering Michael L. Roukes, the co-director of the Kavli Nanoscience Institute.

“The next generation of instrumentation for the life sciences – especially those for systems biology, which allows us to reverse-engineer biological systems – must enable proteomic analysis with very high throughput. The potential power of our approach is that it is based on semiconductor microelectronics fabrication, which has allowed creation of perhaps mankind's most complex technology,” Roukes says.

In the future, the new system will be able to record mass differences equivalent to the weight of a single hydrogen atom, but those accomplishments are now impossible on account of the fact that the technologies used to pick up the NEMS resonator signals are too “noisy”. With nanowire-based circuitry in place, the number of applications for nanoscale mass spectrometry will increase considerably.