Development of a Single Particle Analyzer of Mass and Mobility

Mass spectrometry (MS) is an important analytical tool for obtaining information about the identity, structure and function of molecules over a wide range of sizes, from small molecules up to large protein complexes. Conventional MS techniques work by measuring the mass to charge ratio (m/z) of an ensemble of ions, then using the spacing between different m/z peaks to find the ion charge states so that the masses can be determined. This approach can be difficult to use for samples with a molecular mass beyond ~1 MDa or made up of a heterogeneous mixture of molecules with similar masses, which are typically detected as a single broad, unresolved m/z peak for which the charge cannot be obtained. These samples can instead be weighed with single ion MS, in which the m/z and charge of each ion is measured individually, so other ions do not interfere with the mass measurement. The work described in this dissertation is focused on developing a new instrument for single ion MS that uses charge detection mass spectrometry (CDMS) to better analyze samples that are difficult to measure with conventional MS. New instrumentation and data analysis techniques to improve the precision of CDMS mass measurements and use CDMS for new types of measurements are demonstrated. In CDMS, ions are detected by the charge they induce as they fly through a conducting tube. A new type of CDMS detector with four detector tubes inside an ion trap is used to increase the number of measurements of each ion and reduce the uncertainty in the m/z and charge by signal averaging. A method to measure the ion energy during the trapping time from the signal pattern the ion produces was also developed. This enables the energy and mass of the ion to be determined after collisions with the background gas and after fragmentation events, as in tandem MS. The energy lost to collisions can be used to obtain information about the collision rate and size of the ions, as in ion mobility spectrometry. Monitoring the ion energy also makes it possible to normalize charge measurements for the effect of energy, improving the precision of mass measurements in CDMS