| The work detailed in this dissertation can be broken up into three categories: (1) the development and characterization of novel ion activation techniques, (2) the implementation of various ion activation techniques on a hybrid QLT-oribtrap mass spectrometer, and (3) the application of novel mass spectrometry instrumentation towards large-scale LC-MS/MS based proteome analysis.;In chapter one I provide a brief introduction into the areas of hybrid mass spectrometry and mass spectrometer based ion activation. In chapters two through four I describe our efforts to implement electron transfer dissociation on a hybrid QLT-orbitrap mass spectrometer. The resulting ETD enabled QLT-orbitrap has proven to be a boon for molecular biologist---selling over 150 instruments worldwide.;In chapter five I compare the utility of QLT and orbitrap m/z analysis of tandem MS product ions. In chapters six and seven I detail two novel ion activation strategies (i.e., ion attachment and electron transfer with supplemental CAD---EtcaD). Finally, in chapter eight I present an original LC-MS/MS method that is based around a decision tree algorithm. This algorithm uses information in the MS1 analysis to make real-time, unsupervised, data-dependent decisions concerning what dissociation method to employ. |
