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. 2023 Aug 2;34(8):1731-1740.
doi: 10.1021/jasms.3c00177. Epub 2023 Jul 19.

Electrostatic Linear Ion Trap Optimization Strategy for High Resolution Charge Detection Mass Spectrometry

Daniel Y Botamanenko  1   2 , David W Reitenbach  1 , Lohra M Miller  1 , Martin F Jarrold  1
Affiliations

Electrostatic Linear Ion Trap Optimization Strategy for High Resolution Charge Detection Mass Spectrometry

Daniel Y Botamanenko et al. J Am Soc Mass Spectrom. .

Abstract

Single ion mass measurements allow mass distributions to be recorded for heterogeneous samples that cannot be analyzed by conventional mass spectrometry. In charge detection mass spectrometry (CD-MS), ions are detected using a conducting cylinder coupled to a charge sensitive amplifier. For optimum performance, the detection cylinder is embedded in an electrostatic linear ion trap (ELIT) where trapped ions oscillate between end-caps that act as opposing ion mirrors. The oscillating ions generate a periodic signal that is analyzed by fast Fourier transforms. The frequency yields the m/z, and the magnitude provides the charge. With a charge precision of 0.2 elementary charges, ions can be assigned to their correct charge states with a low error rate, and the m/z resolving power determines the mass resolving power. Previously, the best mass resolving power achieved with CD-MS was 300. We have recently increased the mass resolving power to 700, through the better optimization of the end-cap potentials. To make a more dramatic improvement in the m/z resolving power, it is necessary to find an ELIT geometry and end-cap potentials that can simultaneously make the ion oscillation frequency independent of both the ion energy and ion trajectory (angular divergence and radial offset) of the entering ion. We describe an optimization strategy that allows these conditions to be met while also adjusting the signal duty cycle to 50% to maximize the signal-to-noise ratio for the charge measurement. The optimized ELIT provides an m/z resolving power of over 300 000 in simulations. Coupled with the high precision charge determination available with CD-MS, this will yield a mass resolving power of 300 000. Such a high mass resolving power will be transformative for the analysis of heterogeneous samples.

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Conflict of interest statement

The authors declare the following competing financial interest(s): Two of the authors (D.Y.B. and M.F.J.) are shareholders in Megadalton Solutions, a company that is engaged in commercializing CD-MS. D.Y.B. is an employee of Megadalton Solutions, and M.F.J. is a consultant for Waters.

Figures

Figure 1.
Figure 1.
High resolution measurements with the Gen6 trap. (a) SIMION model of the Gen6 trap. (b) m/z spectrum measured for ubiquitin using the high resolution Gen6 potentials. Insets show Gaussian fits to the two most intense peaks. (c) Mass distribution measured for HBV T = 4 capsids.
Figure 2.
Figure 2.
Simple model of an electrostatic linear ion trap with two opposing ion mirrors separated by a grounded FFR. Potentials are applied to the outermost electrodes which generate a reflecting field. An oscillating ion (shown in red) travels a distance x1 in time t1 through the FFR and a distance x2 in time t2 in the mirror. The FFR has grids to ensure a uniform electric field in the mirror.
Figure 3.
Figure 3.
Identifying regions of trajectory and energy independence for the simplex optimized ion trap. The m/z percent deviation for each trajectory is plotted against the ion energy. The color of each point represents the angular divergence of the ion at the beginning of the trajectory (see text). The color code is shown in the inset. The ions have an m/z of 25 704.58 Da.
Figure 4.
Figure 4.
Achieving energy independence by adjusting the FFR length. Percent m/z deviation plotted against percent energy deviation from the nominal value of 130 eV/z for FFR lengths of (a) 6.604 cm and (b) 9.144 cm. (c) Plot of the slope, %Δ(m/z)/%ΔE, versus FFR length to find the length that minimizes the m/z dependence on the ion energy.
Figure 5.
Figure 5.
m/z percent deviation for each trajectory plotted against the ion energy for an optimized ion trap where the energy- and trajectory-independent points coincide at an ion energy of 130 eV/z. The color of each point represents the angular divergence of the ion at the beginning of the trajectory (see text). The color code is shown in the inset.
Figure 6.
Figure 6.
m/z spectrum determined from 5000 simulated single ion trapping events with the optimized ion trap.
Figure 7.
Figure 7.
Determination of the optimum detection cylinder length. (a) The average charge determined from the simulated signal and (b) the charge RMSD for 5000 simulated single ion trapping events are plotted against the detection cylinder length.
Figure 8.
Figure 8.
Simulated mass spectra for trapping events containing one to eight 5 MDa ions. The mass resolving power decreases linearly from around 300 000 for one ion to 75 000 for eight ions.
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