The Development and Characterization of Ion Detectors and Levitated Ion Sources for Time-of-Flight Mass Spectrometry

Mass spectrometry (MS) plays an important role in the analysis of complex protein samples, which is performed primarily with two strategies: the bottom-up and top-down approaches. The latter has the advantage of preserving the crucial protein-level information by directly analyzing the intact proteins. Time-of-flight (TOF) mass spectrometry is heavily employed in intact protein detection due to its compatibility with the high m/z range of singly charged proteins produced by matrix-assisted laser desorption/ionization (MALDI). However, a significant challenge in TOF-MS is the limited efficiency of detecting large and slow-moving protein ions. Part of the reason lies in the TOF detectors. Conventional detectors, i.e. electron multipliers and microchannel plate (MCP) detectors, are based upon the generation of secondary electrons at ion collision, which is well known to have a decreasing efficiency as the ion velocity decreases. This relationship between ion mass and ion detection efficiency is characterized in detail. The response of an MCP detector as a function of ion mass and acceleration voltage was characterized, for singly charged peptide/protein ions ranging from 1 to 290 kDa in mass, and for acceleration voltages from 5 to 25 kV.;New types of detectors are under development to overcome the detection limit for large molecules. We are developing a novel nanomembrane detector, which contains a freestanding nanomembrane that responds to ion collisions with field emission current changes. The detection efficiencies and mechanisms of different nanomembranes for 9 peptide/protein samples at various acceleration voltages were explored in a MALDI-TOF instrument.;Atmospheric aerosols have serious influences on our climate and health. Understanding of their formation is important but difficult with current research tools. We are developing a novel experimental approach that combines optical tweezers for droplet levitation with control of gas-phase composition and droplet analysis using TOF mass spectrometry. MS analysis of a levitated droplet in a Bessel beam optical tweezers was performed using electrospray ionization and mass spectra of the analyte in the droplet were obtained.