Dual source ion mobility-mass spectrometer for direct comparison of electrospray ionization and MALDI collision cross section measurements

Abstract

In this report, we describe a dual ionization source ion mobility-mass spectrometer (IM-MS) instrument platform for investigations that critically compare ion mobility collision cross section (CCS) measurements obtained from different ionization methods. The instrument incorporates both matrix-assisted laser desorption ionization (MALDI) and nanoelectrospray ionization (nESI) sources. The nESI source incorporates a keyhole geometry ion funnel design which facilitates axial ion focusing, accumulation, and generation of short duration (10-30 mus) ion pulses for use with the IM-MS. The IM-MS instrument operation is independent of which ionization source is used. This allows comparisons of collision cross section measurements to be made between both ion sources with minimal differences in the instrumental arrangement. The performance of the nESI ion source is evaluated by measuring the collision cross section values of the charge states of equine cytochrome c (z = 9-16), and values are in good agreement (<2% deviation) with those previously reported in the literature. Several charge states (z = 8-11) of cytochrome c exhibit multiple cross sectional features in the ion mobility analysis. An analysis of the tryptic peptides of cytochrome c formed by both ESI and MALDI demonstrate that, on average, +1 MALDI ions are similar in CCS to +1 ESI ions and are smaller than +2 ESI ions. The ion mobility resolving power with ESI (30-35) is comparable to that obtained using MALDI (35-40), which suggests that both sources produce sufficiently narrow ion pulses for the measurement to be predominately diffusion rather than gate pulse width limited.

Figure 1

A schematic diagram of the IM-MS with interchangeable (A) MALDI and (B) ESI ionization source modules.

Figure 2

(A) A 3D model of the keyhole ion funnel and (B) ion trajectories through the funnel with the last electrode set for ion accumulation. The five regions of the ion funnel and simulation parameters are discussed in the text. (C) A multidimensional plot of calculated ion position, time and kinetic energy for 20 ions of 1000 m/z as they traverse the keyhole ion funnel.

Figure 3

(A) Ion trajectories for 20 ions of various m/z values illustrating the loss in focusing abilities for increasingly larger m/z. At 20000 m/z and 3 torr, the electric field is ineffective at refocusing ions to the center of the device. (B) Increasing the pressure from 3 to 5 torr effectively dampens the ion’s kinetic energy such that its trajectory can be favorably altered. Simulation conditions are: 50 V RF, 60 V DC across funnel, 20 V stopping potential, helium background gas.

Figure 4

(A) A 2-dimensional ion mobility-mass plot of ESI generated cytochrome c ion charge states. (B) The corresponding ion mobility arrival time distributions for each of the observed charge states of cytochrome c. (C) An IM-MS 2D plot of the tryptic peptides of cytochrome c obtained with ESI.