Development of an Electrostatic Linear Ion Trap for Tandem Mass Spectrometry
The electrostatic line ion trap (ELIT) is a relatively new type of mass analyzer in which ions are axially confined between two opposing ion mirrors. Image charge induced on a central pick-up electrode can be digitized, mass analyzed, and calibrated to produce a mass spectrum. Recent improvements to the ELIT and the development of a novel high resolution, high efficiency ion isolation method have given new life to the use of the ELIT as high-performance tandem mass spectrometer. This dissertation outlines advancements in all areas of tandem mass spectrometry (ion isolation, probing ions, and mass analysis) using an electrostatic linear ion trap.
An introduction to the ELIT and the analytical techniques associated with the device is discussed in Chapter 1. Next, Chapters 2 and 3 discuss innovations in the realm of mass analysis using an ELIT. Following discussion of the mass analyzer, Chapter 4 discusses a novel high resolution, high efficiency method for ion isolation. Chapter 5 then discusses an extension of the fore-mentioned ion isolation method in which multiple ions can be isolated simultaneously. Finally, Chapter 6 discusses tandem mass spectrometry experiments that have been done with the current iteration of the ELIT.
In Chapter 2, the ELIT was configured to allow for the simultaneous acquisition of mass spectra via Fourier transform (FT) techniques (frequency measurement) and via time-of-flight (TOF; time measurement). In the former case, the time-domain image charge derived from a pick-up electrode in the field free region of the ELIT is converted to frequency-domain data via Fourier transform (FT-ELIT MS). The ELIT geometry facilitates the acquisition of both types of data simultaneously because the detection schemes are independent and do not preclude one another. The two MS approaches exhibit a degree of complementarity. Resolution increases much faster with time with the MR-TOF approach, for example, but the closed-path nature of executing the MR-TOF in an ELIT limits both the m/z range and the peak capacity. For this reason, the FT-ELIT MS approach is most appropriate for wide m/z range applications, whereas MR-TOF can provide advantages in a “zoom-in’ mode in which moderate resolution (M/ΔMfwhm≈ 10,000) at short analysis time (10 ms) is desirable.
In Chapter 3, the mass resolution of the FT-ELIT experiment is increased by reducing the axial length of the ELIT. Mass resolution increases linearly with frequency. For an equivalent transient length, which implies an equivalent path length, resolution is higher in a shorter ELIT. Relative changes in the m/z range were also explored. When trapping ions using mirror switching, the m/z range is determined by the time required for fast ions to enter and exit the trap (one reflection), and the time it takes slow ions to enter the trap. By reducing the length of the FT-ELIT mass spectrometer while maintaining a constant distance from the point ions are initially accelerated to the first ion mirror, only the low m/z limit is affected for a given mirror switching time. Both a 2.625” and a 5.25” trap will be examined and compared.
In Chapter 4, ion isolation was achieved via selective pulsing of the entrance and exit ion mirrors in an electrostatic linear ion trap mass spectrometer. In addition to ion capture, mirror switching can also be used as a method for ion isolation of successively narrower ranges of mass-to-charge (m/z) ratio. By taking advantage of the spatial separation of ions in an ELIT device, pulsing of the entrance and/or exit mirrors can release unwanted ions while continuing to store ions of interest. Furthermore, mirror switching can be repeated multiple times to isolate ions of very similar m/z values with minimal loss of the stored ions. As isolation is accomplished due to the spatial/temporal separation of ion packets within the ELIT, multiple MR-TOF spectra are shown to demonstrate separation in the ELIT at the time of isolation. An isolation resolution of greater than 36,000 is demonstrated here using a 5.25” ELIT. This resolution corresponds to the fwhm resolution necessary to reduce contaminate overlap of an equally abundant adjacent ion to 1% or less of the isolated ion intensity.
In Chapter 5, advantage is taken of the ion overlapping phenomenon in an ELIT to enable the simultaneous isolation of ions of disparate m/z ratios using mirror switching. This process is demonstrated with minimal ion loss using the isotopologues of three carborane compounds ranging in m/z from 320 to 1020. Simultaneous isolation is demonstrated with the isolation of two and three peaks in separate isotopic distributions as well as with isolation of alternating isotopologues within the same distribution. Such simultaneous isolation experiments are particularly useful when conducting experiments in which a mass calibrant is needed or when multiplexing in a tandem MS workflow.
Chapter 6 discusses the use of the current ELIT as a tandem mass spectrometer. Tandem mass spectrometry (MS/MS or MSn) is the sequential mass spectrometric analysis of analyte ions. Product ions are often informative and can provide information about the structure and identity of the precursor ion. The use of the electrostatic linear ion trap as both a tandem-in-space and tandem-in-time mass spectrometer is demonstrated. The quadrupole linear ion trap (QLIT) located colinear to the ELIT can be used for apex isolation, collision induced dissociation (CID), and ion acceleration for mass analysis in the ELIT. As a tandem-in-space device, isolation and CID are accomplished in the QLIT prior to product ion analysis in the ELIT. When operated as a tandem-in-time mass spectrometer, mirror switching can be used for high resolution, high efficiency isolation. Post-isolation, ions are subjected to surface induced dissociation using a gold disk placed directly behind plate 8. Ions still within the kinetic energy focusing range of the ELIT after fragmentation are re-trapped for product ion analysis.
- Doctor of Philosophy
- West Lafayette