Physicochemical Property Correlations with Ionization Efficiency in Capillary Vibrating Sharp-Edge Spray Ionization (cVSSI)

Abstract

The relative contributions to ionization efficiency by three molecular chemical properties have been examined for field-free and field-enabled capillary vibrating sharp-edge spray ionization (cVSSI) using mass spectrometry (MS) analysis. Ion intensities have been recorded for model compounds under each operational ionization mode as well as for aqueous and nonaqueous (methanol) solvent systems. Multiple regression analysis suggests that for field-free cVSSI, ion intensity is mostly associated with the log of the base dissociation constant (pK b) and proton affinity (PA) for both aqueous and methanol solutions. Comparatively, for field-enabled cVSSI using aqueous solutions, the dominant factor correlated with ion intensity is the log of the partition coefficient (log P). To a lesser degree, this is observed for methanol solutions as well. For ESI, pK b is the dominant factor associated with ion signal levels from methanol and aqueous solutions. These results are supported by studies conducted on two different mass spectrometers employing different cVSSI emitter tips. The relationship of ion intensity and pK b in ESI is supported by multiple studies; however, the shift to other chemical properties with the addition of cVSSI suggests the possibility that a different (or combinations of) ionization mechanism(s) may be operative for these ionization modes. These results are briefly considered in light of the different ESI mechanisms.

Combining Field-Enabled Capillary Vibrating Sharp-Edge Spray Ionization with Microflow Liquid Chromatography and Mass Spectrometry to Enhance ‘Omics Analyses

“…Notably, sample nebulization is achieved only over a very narrow frequency range (±1 kHz). Additionally, previous measurements of droplet diameters (aqueous) produced by tips with similar internal diameters show a size distribution centered at ∼15–25 μm, which is independent of operational frequency …”

“…Because these ions elute under isocratic conditions, a question arises as to whether or not such observations can be used to better understand differences in ionization processes. In a previous study, the relative ionization efficiencies of a number of amino compounds were compared for experiments employing voltage-free cVSSI, field-enabled cVSSI, and ESI . The studies also compared results for aqueous and methanol samples.…”

“…Additionally, such an angle provides clearance that is sufficient for coupling the PTFE tubing such that it does not affect the vibration of the glass slide. For these experiments, all device parameters (e.g., emitter tip angle and length) were maintained as precisely as possible in order to provide reproducible droplet size distributions; typically, cVSSI nebulization of aqueous sample using similar flow rates produces average droplet sizes of ∼15 to ∼25 μm. , …”

“…Additionally, previous measurements of droplet diameters (aqueous) produced by tips with similar internal diameters show a size distribution centered at ∼15−25 μm, which is independent of operational frequency. 75 The pulled glass tip is glued to the microscope slide typically at a 45−75°angle relative to the distal edge of the slide (Figure 1). Iterative testing revealed that such an arrangement provides the most robust nebulization.…”

“…Presumably, this produces a more expansive area from which solvent streaming may occur. Notably, the employment of the sharp edges in VSSI and cVSSI is what allows for such high efficiency nebulization with very little power requirements (see below). − …”