A novel high-frequency alternating current (AC) electrospray ionization (ESI) source has been developed for applications in mass spectrometry. The AC ESI source operates in a conical meniscus mode, analogous to the cone-jet mode of direct current (DC) electrosprays but with significant physical and mechanistic differences. In this stable conical-meniscus mode at frequencies greater than 50 kHz, the low mobility ions, which can either be cations or anions, are entrained within the liquid cone and ejected as droplets that eventually form molecular ions, thus making AC ESI a viable tool for both negative and positive mode mass spectrometry. The performance of the AC ESI source is qualitatively shown to be frequency-dependent and, for larger bio-molecules, the AC ESI source produced an ion signal intensity that is an order of magnitude higher than its DC counterpart. in mass spectrometry (MS) has revolutionized the study of proteins and peptides and contributed significantly to biological and biomedical research. In contrast to ionization techniques such as fast atom bombardment (FAB), electron impact (EI), and thermal ionization that tend to fragment large molecules, ESI and MALDI minimize fragmentation, hence making them appropriate for analysis of biomolecules [3,4], polymeric macromolecules [5], and the study of the environmental implications of hazardous materials [6]. The operating principle of ESI is that it generates charged droplets from the tip of a static conical liquid structure [7] known as Taylor's cone [8]. These charged droplets, containing analyte molecules present in the liquid, eventually form molecular ions by either multiple Raleigh fission events or, alternatively, via the charge residue mechanism [9]. In this study, we introduce another variant of ESI that is obtained by application of high-frequency alternating current (AC) potential to generate charged droplets for mass spectrometry.In previous studies by the authors' group, it has been shown that in a certain window of frequency-voltage phase space, a steady, slender conical meniscus [10 -12] is obtained using a high-frequency AC electrospray. As shown in Figure 1b, these AC cones, which have a half cone angle of ϳ11°and exhibit a continuous longitudinal growth in time are significantly different from static DC Taylor cones (with half cone angle ϳ49°), pulsating electrosprays [13], or low-frequency (Ͻ10 kHz) AC electrosprays [14] (Supplementary Material showing an AC cone of ethanol solvent at an applied AC potential of frequency 80 kHz and magnitude ϳ 5.5 kV (peak to peak) along with the preliminary sensitivity curve and positive mode mass spectra of cytochrome c, which can be found in the electronic version of this article). The formation of the AC cone is due to the difference in the mobility of liquid phase anions and cations that leads to a build up of the low mobility species in the cone because of insufficient time to relax onto the surface of the meniscus when the AC signal switches polarity-a condition induced when the inverse r...
The half-angle of an ac cone is shown to exhibit a universal (length-scale independent) asymptotic value of 12.6 degrees at high-permittivity ratio, which is quite distinct from the 49.3 degrees of dc Taylor cones. Our theory and experiments suggest that ac entrainment of low-mobility anions, generated by field-assisted ion dissociation, sustains a net charge at the ac cone. Mutual Coulombic repulsion between these free charges compensates the singular azimuthal capillary force and elongates the cone with an axial force that does not exist in dc cones.
The novel effects resulting from the entrainment of low mobility ions during alternating current (ac) electrospray ionization are examined through mass spectrometry and voltage/current measurements. Curious phenomena such as pH modulation at high frequencies (>150 kHz) of an applied ac electric field are revealed and explained using simple mechanistic arguments. Current measurements are utilized to supplement these observations, and a simplified one-dimensional transient diffusion model for charge transport is used to arrive at a scaling law that provides better insight into the ac electrospray ionization process. Moreover, because of the different pathway for ion formation in comparison to direct current (dc) electrospray, ac electrospray (at frequencies >250 kHz) is shown to reduce the effects of ionization suppression in a mixture of two molecules with different surface activities.
A series of studies comparing the performance of alternating current electrospray ionization (AC ESI) mass spectrometry (MS) and direct current electrospray ionization (DC ESI) MS has been conducted, exploring the absolute signal intensity and signal-to-background ratios produced by both methods using caffeine and a model peptide as targets. Because the high-voltage AC signal was more susceptible to generating gas discharges, the operating voltage range of AC ESI was significantly smaller than that for DC ESI, such that the absolute signal intensities produced by DC ESI at peak voltages were 1 - 2 orders of magnitude greater than those for AC ESI. Using an electronegative nebulizing gas, sulfur hexafluoride (SF6), instead of nitrogen (N2) increased the operating range of AC ESI by ~50%, but did not appreciably improve signal intensities. While DC ESI generated far greater signal intensities, both ionization methods produced comparable signal-to-background noise, with AC ESI spectra appearing qualitatively cleaner. A quantitative calibration analysis was performed for two analytes, caffeine and the peptide MRFA. AC ESI utilizing SF6 outperforms all other techniques for the detection of MRFA, producing chromatographic limits of detection nearly one order of magnitude lower than that of DC ESI utilizing N2, and one half that of DC ESI utilizing SF6. However, DC ESI outperforms AC ESI for the analysis of caffeine, indicating improvements in spectral quality may benefit certain compounds, or classes of compounds, on an individual basis.
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