Single Particle Mass Spectrometry and Inertial Imaging with Nanomechanical Systems

Citation

Kelber, Scott Ian (2013) Single Particle Mass Spectrometry and Inertial Imaging with Nanomechanical Systems. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9PN93MP. https://resolver.caltech.edu/CaltechTHESIS:06122013-133415217

Abstract

This thesis work describes the development of a new technology for mass spectrometry using nanoelectromechanical systems (NEMS-MS). Mass spectrometry is a technique used to identify molecules through mass measurement. Nanoelectromechanical systems (NEMS) feature low cost, scalable on-chip compatibility, and are highly sensitivity to the mass of accreted species. Using NEMS devices, we perform NEMS-MS where the inertial mass of individual molecules is directly measured. This contrasts with traditional MS techniques utilizing electromagnetic fields to measure the average mass-to-charge ratio of many molecules.

Initially, an ultra-high-vacuum apparatus is constructed to perform NEMS-MS using laser desorption techniques for molecule delivery. An existing technique, matrix assisted laser desorption ionization (MALDI), is implemented without the usual ion optics system in order to permit detection of neutral and ionized particles. This, however, is found to be incompatible with NEMS-MS due to the matrix background. The MALDI-NEMS-MS system is then used to measure gold nanoparticles that simultaneously act as the matrix and analyte. These experiments are combined with measurements of IgM antibodies using an ESI (electrospray ionization)-NEMS-MS system to demonstrate single-particle nanomechanical mass spectrometry in real time.

Then, the laser desorption-based NEMS-MS system is upgraded to implement laser induced acoustic desorption (LIAD) for particle delivery. LIAD is a matrix-free technique in the mass spectrometry community for desorbing nonvolatile, thermally labile molecules. The LIAD-NEMS-MS system is used for the direct mass measurement of several different types of proteins and protein-complexes with single-protein quantification. Additionally, experimental data is presented that suggests the movement of surface-adsorbed particles along the device surface due to the vibration of the resonant device modes; this remains to be confirmed.

Finally, a new methodology, inertial imaging theory, is presented, which enables measurement of the mass and shape of adsorbed particles on a NEMS device. The shifts induced by particle adsorption in the modal frequencies of a resonant device are used to calculate the spatial moments of mass distribution of individual adsorbates, one-by-one, as they adsorb It is shown that the ultimate resolution in particle size of this technique is limited only by fundamental noise processes in the device and not wavelength-dependent diffraction effects. Indeed, atomic resolution is possible using existing NEMS devices.

Thesis Files