MANIPULATION AND ANALYSIS OF INTACT PROTEIN IONS USING A PURELY DUTY CYCLE – BASED, DIGITALLY OPERATED QUADRUPOLE MASS FILTER (DQMF) AND ACCELERATION QUADRUPOLE TIME-OF-FLIGHT (Q-TOF) MASS SPECTROMETER
MetadataShow full item record
Mass spectrometry is one of the most widely used analytical tools for analysis of proteins and other biological molecules. It provides information like mass, quantity and structure and it can readily be coupled with other analytical methods. However, the traditional mass spectrometry systems do have limitations regarding handling, resolving, and accurately determining the mass of large, intact, low charge biomolecules. Digital quadrupole mass spectrometers have demonstrated the ability of improved resolving power at high mass. Additionally, digital waveform generation technology has advanced enough to provide first comparator-based, duty-cycle controlled quadrupole mass filter. This instrument relays on precise control of frequency and duty cycle instead of voltage, which means there is no theoretical upper mass limit that can be measured. It provides new methods of mass analysis, which are inherently challenging for sinusoidally driven systems. Chapter one introduces the concept and the abilities of the digital waveform technology. It provides a background on a digital mass filter and compares it to the traditional operating modes. Chapter two discusses new approaches that maximize ion transport efficiency while minimizing solvent clustering at the same time. It examines the conditions and methods for optimal digital waveform operation of a mass filter to minimize solvent clustering. Chapter three continues to explore digital waveform capabilities of a mass filter. The measured response of the ion distribution as a function of axial ejection conditions is a focus of this study. The energy imparted to the ion by the duty cycle based ejection, is essentially equivalent going to and out of the axial potential well. Chapter four further explores digital waveform abilities. It is presented as a tutorial on digital waveforms, stability diagrams and pseudopotential well plots. The experimental results in stability zones A and B are presented along with advantages of mass filter operation without any DC potential between the electrodes. The final chapter experimentally demonstrates collision-induced dissociation of ions in a digital linear ion trap. The isolation of a target ion is achieved in two steps followed by excitation by changing the duty cycle and/or frequency of the trap.