10.25394/PGS.12015783.v1
Joshua T Johnson
Joshua T
Johnson
Development of an Electrostatic Linear Ion Trap for Tandem Mass Spectrometry
Purdue University Graduate School
2020
mass spectrometry instrumentation
Electrostatic Linear Ion Trap
Tandem Mass Spectometry
Ion Isolation
mass spectrometry approaches
Analytical Chemistry not elsewhere classified
Analytical Spectrometry
2020-03-23 11:52:52
Thesis
https://hammer.purdue.edu/articles/thesis/Development_of_an_Electrostatic_Linear_Ion_Trap_for_Tandem_Mass_Spectrometry/12015783
<p>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.</p>
<p>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.</p>
<p>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 <i>m/z</i> range and
the peak capacity. For this reason, the FT-ELIT MS approach is most appropriate
for wide <i>m/z</i> range applications,
whereas MR-TOF can provide advantages in a “zoom-in’ mode in which moderate
resolution (M/ΔM<sub>fwhm</sub>≈ 10,000) at short
analysis time (10 ms) is desirable.</p>
<p>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 <i>m/z</i> range were also explored. When
trapping ions using mirror switching, the <i>m/z</i>
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 <i>m/z</i> limit is affected
for a given mirror switching time. Both a 2.625” and a 5.25” trap will be
examined and compared.</p>
<p>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 (<i>m/z</i>) 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 <i>m/z</i> 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.</p>
<p>In Chapter 5,
advantage is taken of the ion overlapping phenomenon in an ELIT to enable the simultaneous
isolation of ions of disparate <i>m/z</i>
ratios using mirror switching. This process is demonstrated with minimal ion
loss using the isotopologues of three carborane compounds ranging in <i>m/z</i> 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.</p>
<p>Chapter 6
discusses the use of the current ELIT as a tandem mass spectrometer. Tandem
mass spectrometry (MS/MS or MS<sup>n</sup>) 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.</p>
<br>