Technology.am (July 23, 2009) — Physicists at the California Institute of Technology have developed a technique to determine the mass of a single molecule, in real time by using devices millionths of a meter in size.
The mass of molecules is traditionally measured using mass spectrometry, in which samples consisting of tens of thousands of molecules are ionized, to produce charged versions of the molecules, or ions. Those ions are then directed into an electric field, where their motion, which is choreographed by both their mass and their charge, allows the determination of their so-called mass-to-charge ratio. From this, their mass can ultimately be ascertained.
The new technique simplifies and miniaturizes the process through the use of very tiny nanoelectromechanical system (NEMS) resonators. 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, 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.
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.
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.
The NEMS mass spectrometers, which could determine the masses of hundreds of thousands of molecules “in an instant.