STRATEGIES TO ENHANCE SENSITIVITY AND ENABLE TANDEM MASS ANALYSIS OF BIOMOLECULES USING DIGITAL WAVE TECHNOLOGY

Fatima Olayemi Obe

doi:10.7273/000007442

Digital wave technology (DWT) is an emerging and promising technique in mass spectrometry (MS) instrumentation, which has been alluded to as “the future of mass spectrometry.” The DWT discriminates charged ions for mass filtering using a rectangular waveform rather than a sine wave used in traditional mass filters. The unique advantages presented by the DWT, which include limitless mass range, low voltage requirement, and handling flexibility, have positioned it as a potential alternative to sinewave-driven systems. This work takes advantage of the flexibility of the digital waveform duty cycle variations of the DWT to improve the mass resolution of the digital waveform systems with a major goal of converting the so-called “low resolution” quadrupole instruments into a medium-high resolution mass filter. Hence, this work covers the development and application of a digital tandem quadrupole mass filter (DTMF) in analyzing biomolecules. A DTMF uses two low-resolution quadrupole mass filters aligned in series to create a new stability mass window whose width corresponds to the resolution of the isolated ion. This stability window can be narrowed by adjusting the duty cycle of the digital waveforms applied to the quadrupole rods to improve mass resolution. Chapter one of this work introduces the background of the quadrupole mass filters, the digital wave systems with attractive features and capabilities, and the digital tandem mass filters. A new technique that helps to improve ion transmission into the higher Mathieu stability zones – the digital pre-filter was also introduced. Chapter two focuses on developing the DTMF instrumentation and the initial testing of its applicability in analyzing low-mass molecules. This chapter covers the experimental evaluation of the DTMF principles and optimization of the operational parameters. Chapter three explored the application of the DTMF in analyzing peptides and proteins using a soft ionization technique. This chapter investigates the compatibilities of the DTMF with the native analysis of proteins and its potential in the analysis of large biomolecules. Chapter four covers the studies of the digital pre-filter (DPF), a new technique enabled by the DWT. This work presents the operational principles, performance optimization, and the experimental evaluation of the DPF. Overall, this project accomplished the use of digital wave technology to improve the mass resolution of a quadrupole mass filter through the development of a digital tandem quadrupole instrument, thereby increasing the boundary of the quadrupole instrument usage, examined a native quadrupole MS analysis of proteins with the digital wave system to enable biomolecule analysis, and developed a new method of sensitivity improvement for higher stability zones accessibility.

STRATEGIES TO ENHANCE SENSITIVITY AND ENABLE TANDEM MASS ANALYSIS OF BIOMOLECULES USING DIGITAL WAVE TECHNOLOGY

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