Development of an Electrostatic Linear Ion Trap as a Standalone Tandem Mass Spectrometer.pdf

In mass spectrometry, analyte molecules are ionized by various mechanisms, such that they can be manipulated by electric and magnetic fields. By performing such manipulations, the mass to charge (m/z) ratio of the analyte molecules can be measured. Many methods for ion manipulation that allow for such m/z determination have been developed in the form of different mass analyzers. These include but are not limited to magnetic/electric sector instruments, time-of-flight (TOF) mass analyzers, 3D quadrupole ion traps, quadrupole mass filters, linear quadrupole ion traps (LITs), Fourier-transform ion cyclotron resonance (FT-ICR) instruments, Orbitrap mass analyzers, and electrostatic linear ion traps (ELITs). Each of these mass analyzers has unique advantages and disadvantages resulting from its specific mechanism of operation, allowing each of these to find a niche in mass spectrometry applications. The ELIT is a mass analyzer composed of two opposing ion mirrors, which cause trapped high energy ions to oscillate along a linear axial trajectory. The oscillation period of ions in the ELIT is dependent on injection energy, the potential energy and electrode geometry of the ELIT, and the ion m/z ratio. As such, mass spectra can be measured by measuring the frequency of ion packets in the ELIT in Fourier-transform (FT) operation mode, or by or by allowing ions to separate spatially in an m/z dependent manner before detection via a microchannel plate (MCP) in multiple-reflection time-of-flight (MR-TOF) mode of operation. The ability to perform two orthogonal mass analysis techniques in a single mass analyzer is one key advantage of the ELIT. Both FT-MS, and MR-TOF mode of operation are high-resolution techniques, making the ELIT unique in its excellent performance characteristics despite low complexity and manufacturing cost. Additionally, the ELIT can be used to perform high-resolution ion isolations, which makes it especially attractive for tandem-MS.

In chapter 1, the operating principles for MR-TOF and FT-MS modes of operation in an ELIT are discussed. In chapter 2 and 3, the performance, limitations, and applications of the mirror-switching isolation technique in the ELIT are discussed. Given the high-resolution performance of the ELIT for both mass analysis and ion isolation, it is clear that the ELIT has great potential for tandem-MS applications which require high-resolution in either the precursor selection, mass analysis step, or both. In chapters 4, 5, and 6, the implementation and development of infrared multi-photon dissociation, and surface-induced dissociation techniques in the ELIT are discussed, and it is shown that the ELIT can be used to as a standalone tandem mass spectrometer. While not performed on the ELIT instrument, the charge-based valet parking technique discussed in chapter 7 applies to tandem-MS as a whole, as it is shown to improve fragment yield in ETD. Finally, in chapter 8, the future directions of development for the ELIT mass analyzer are discussed.