Caltech physicists have created a mass spectrometer capable of measuring individual molecules in real time. Current mass spectrometers require specific concentrations of molecules that are larger in size, and today’s devices take up considerably more room than the 2 micrometers long by 100 nanometers wide resonators in the new spectrometer.
The bridge-like resonators, which are 2 micrometers long and 100 nanometers wide, vibrate at a high frequency and effectively serve as the “scale” of the mass spectrometer.
“The frequency at which the resonator vibrates is directly proportional to its mass,” explains research physicist Askshay Naik, the first author of a paper about the work that appears in the latest issue of the journal Nature Nanotechnology. Changes in the vibration frequency, then, correspond to changes in 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,” Naik says.
As described in the paper, the researchers used the instrument to test a sample of the protein bovine serum albumin (BSA), which is known to have a mass of 66 kilodaltons (kDa; a dalton is a unit of mass used to describe atomic and molecular masses, with one dalton approximately equal to the mass of one hydrogen atom).
The BSA protein ions are produced in vapor form using an electrospray ionization (ESI) system.The ions are then sprayed on to the NEMS resonator, which vibrates at a frequency of 450 megahertz. “The flux of proteins reaching the NEMS is such that only one to two protein lands on the resonator in a minute,” Naik says.
When the BSA protein molecule is dropped onto the resonator, the resonator’s vibration frequency decreases by as much as 1.2 kiloHertz-a small, but readily detectable, change. In contrast, the beta-amylase protein molecule, which has a mass of about 200 kDa, or three times that of BSA, causes a maximum frequency shift of about 3.6 kHz.
Because the location where the protein lands on the resonator also affects the frequency shift-falling onto the center of the resonator causes a larger change than landing on the end or toward the sides, for example-“we can’t tell the mass with a single measurement, but needed about 500 frequency jumps in the published work,” Naik says. In future, the researchers will decouple measurements of the mass and the landing position of the molecules being sampled. This technique, which they have already prototyped, will soon enable mass spectra for complicated mixtures to be built up, molecule-by molecule.
Press release: Caltech Physicists Create First Nanoscale Mass Spectrometer…
Image: Progressively magnified scanning electron micrographs showing one of the doubly-clamped beam NEMS devices used in these experiments. It is embedded in a nanofabricated three-terminal UHF bridge circuit.