Nanosystem-based Mass Spectrometry for ultra-high mass biological agents – NEMS-MS

Gravimetric devices permit mass measurements in the macro-world (kilograms to nanograms), whereas mass spectrometers perform mass-to-charge ratio measurements on the infinitesimal scale (attograms to yoctograms). In between these two regimes, lies the “meso-world” where viruses, spores, fungi, bacteria, and cellular organelles lurk. Owing to a lack of appropriate technology, these species have escaped mass measurement until now. NanoElectroMechanical Systems (NEMS) are extremely sensitive to inertial mass of both neutral and ionized individual particles accreting upon their surface, and have unprecedented resolving power in the aforementioned mass range. While proofs of concept of the NEMS-MS principle have been demonstrated, they were performed with cumbersome and low efficiency interfaces that preclude the efficient utilization of these devices to systematically explore the mass range of interest. This proposal presents a plan to develop new delivery vehicles for NEMS, the only devices capable of performing mass measurements in the meso-world regime. The short term goals are to develop Charge Detection Mass Spectrometry-NEMS as well as Surface Acoustic Wave Nebulization-NEMS that will enable the analysis of large, macromolecular systems that are too large to be reliably measured by conventional mass spectrometry. Neither of these approaches has ever been implemented before. Both will target single particle detection, bearing in mind the problem of the small capture cross section for individual bio-nanoparticles. To overcome this and other challenges, a strong consortium has been built between LETI, EDyP and the UPMC. This team has combined expertise in nanosystems, physics, biology and MS instrumentation development. The long term goal of this research is to develop the capability to directly measure with a portable device, the masses of large macromolecular pathogens that pose a bioterrorism threat.