‘Neutral Mass Spectrometry’ Fills Gap In Existing Weighing Technologies

 GRENOBLE, France – Nov. 22, 2018 –

A team of LETI and EDyP researchers, in collaboration with CNRS I2BC, has demonstrated a new mass-spectrometry technology based on nanomechanical resonators that measures the mass of particles previously beyond the reach of current commercial technology, and which they used to measure the mass of a whole bacteriophage virus capsid. The system is described in an article published in Science Magazine in November 2018, “Neutral Mass Spectrometry of Virus Capsids Above 100 Megadaltons with Nanomechanical Resonators”.

Just like guitar strings, nanomechanical resonators “ring” at a specific tone or frequency. Like a guitar player placing his or her finger on a string for a particular tune, a particle landing on the surface of a resonator will change the resonator’s frequency. The mass of the landed particle can then be inferred from this frequency change.

Previous attempts to realize nanomechanical mass spectrometers used electromagnetic fields to transport ionized analytes to the resonator, resulting in poor efficiency. Departing from conventional wisdom, the team found solutions to circumvent ionization altogether:

  • First, they use surface acoustic waves to nebulize nanoparticles in solution into a mist of small droplets, which are then aspirated into a vacuum system.
  • Second, particles are transported and guided towards the nanomechanical detector using a flow of carrier gas that propels and focuses the particles into a narrow beam.
  • As a nanomechanical resonator is still much smaller than the particle beam, the team used not one, but an array of 20 nanomechanical resonators to detect the incoming particles.

In the targeted mass range, particles weigh the equivalent of 1 million to 1 billion hydrogen atoms. It is an intriguing realm, where some particles, just like objects of everyday life, are constituted of an unspecific number of atoms, while others are known to contain specific numbers of atoms of defined masses: like small molecules, they have a defined molecular mass. This is the case, for example, of the bacteriophage T5 virus capsid that the team analyzed. This turned out to be the highest molecular mass ever determined by mass spectrometry.

Bacteriophages (etymologically “bacteria eaters”) are viruses affecting bacteria. These natural predators of bacteria are of high interest to researchers, because the number of antibiotic-resistant bacteria strains has increased at an alarming rate in the past decade, while the number of new antibiotics molecules introduced on the market has decreased. Bacteriophages are considered promising alternatives to standard antibiotherapies, as they can be engineered to target specific pathogenic bacteria. However, they have not reached their full potential yet, partly because of a lack of characterization techniques for those viruses, which cannot be analyzed in their native form by conventional mass spectrometers. The system demonstrated by our team opens prospects to characterize a broad diversity of nanoparticles of biomedical interest.