Hanay, M.S., et al. Nat. Nanotechnol. 7, 602–608 (2012).

Mass spectrometry is the workhorse of the proteomics field, but it is not a single-molecule technique. However, a fundamentally different technology, in the form of nanoelectromechanical systems (NEMS) resonators, is being developed as a kind of single-molecule mass spectrometer. NEMS resonators detect molecular mass with extremely high sensitivity, as the adsorption of a molecule to the resonator causes a jump in the resonant frequency that is proportional to the mass of the molecule. Hanay et al. now show that the NEMS technology can detect the mass of arriving molecules, including gold nanoparticles and human IgM antibodies, in real time as they adsorb to the NEMS resonator. The ability to detect single proteins in real time may eventually open up the possibility of single-cell proteome profiling.