Automated orthogonal control system for electrospray ionization

Abstract

Low-flow electrospray ionization is typically a purely electrostatic method, used without supporting sheath-gas nebulization. Complex spray morphology results from a large number of possible spray emission modes. Spray morphology may assume the optimal Taylor cone-jet spray mode under equilibrium conditions. When coupling to nanobore gradient elution chromatography, however, stability of the Taylor cone-jet spray mode is compromised by the gradient of mobile phase physiochemical properties. The common spray modes for aqueous/ organic mobile phases were characterized using orthogonal (strobed illumination) transmitted light and (continuous illumination) scattered light imaging. Correlation of image sets from these complementary illumination methods provides the basis for spray mode identification using qualitative and quantitative image analysis. An automated feedback-controlled electrospray source was developed on a computer capable of controlling electrospray potential using an image-processing based algorithm for spray mode identification. The implementation of the feedback loop results in a system that is both self-starting and self-tuning for a specific spray mode or modes. Thus, changes in mobile phase composition and/or flow rate are compensated in real-time and the source is maintained in the cone-jet or pulsed cone-jet spray modes. [7]. The principal means of increasing the operable ESI flow rate was with the addition of either coaxial or cross flow sheath gas to aid in the droplet formation suitable for ion generation and mass analysis [8 -10].While much research and development effort was aimed at increasing electrospray's operable flow rate, a number of groups conducted studies at lower flow rates [11][12][13][14]. Early observations by Gale and Smith [11] showed that the flow rate could be reduced to 200 nL/min without reducing the signal-to-noise (S/N) ratio. Wilm and Mann [12,15] demonstrated that flow rates could be reduced another order of magnitude, to the 10 to 20 nL/min level, with no significant reduction in S/N. At approximately the same time, Emmet and Caprioli [13] demonstrated exceptionally high sensitivity for peptide analysis by directly coupling nanobore (50 -100 m inside diameter) LC columns to low-flow (100 -200 nL/min) ESI. Ultra-low flow rates of less than 1 nL/min have been shown to yield significant ion current suitable for MS [14,16] and enable the direct coupling of small bore (Ϸ5 m) capillary electrophoresis, with sub-attomole sensitivity [17]. Collectively, these various nanoliter-per-minute ESI-MS methods have become known as nanospray.Recent experiments suggest that operation at nanospray flow rates effect ionization on a fundamental level. Ionization effects have been observed for both off-line [18,19] and on-line [20] nanospray methods. It is important to note that electrostatic attraction between mobile phase and counter-electrode is typically the sole source of mobile phase flow for off-line nanospray [12,

A Study of Electrospray Ionization Emitters with Differing Geometries with Respect to Flow Rate and Electrospray Voltage

“…Overall, the 50 μm EOEs produced the highest average intensities. The decrease in signal intensity as the voltage is increased with the 50 μm EOE is likely caused by a transition from the cone-jet to the multi-jet mode, as previously reported [42,57]. For the 30 and 50 μm EOEs, it should be noted that the signal stability decreases and the standard deviation of the signal intensity increases as the ESI voltage increases.…”

Nozzle and liquid effects on the spray modes in nanoelectrospray

“…High-speed photography revealed a correlation between the current oscillations and the transient formation of a liquid jet [27]. It has been pointed out that these modes could have an effect on the signal obtained in a mass spectrometer [28][29][30] and that the spray mode can be automatically detected by monitoring the frequency of any pulsations. Each of these findings was found when the electrospray was in a forced flow situation-either using a pump, or by the application of gas pressure to maintain the flow.…”

Stable gradient nanoflow LC-MS

“…Valaskovic® et® al.® [22]® demonstrated® that® the® optimum electrospray potential can vary significantly with solvent composition over the course of a gradient elution nanoLC-MS experiment in the absence of nebulizer assistance.® The® data® in® Figure® 1® show® that® a® single® set® of ion source conditions, initially established under high aqueous conditions, can be chosen to provide optimal operational parameters across a broad solvent composition range typical of gradient operation. In this instance, a nebulizer gas setting of 1.32 L/min and an electrospray potential of Ϫ1400 V would provide maximum stability giving absolute signal intensity within 20% of maximum across the gradient.…”

“…As a result, many of the nanoLC-MS systems described in the literature limit the gradient to avoid solvent conditions comprised of greater than approximately 90% water [15,20,21]. An alternate approach to solve this problem involves an automated control system that monitors the visual image of the spray and adjusts the electrospray potential over the course of a gradient to help stabilize the electrospray process [22].…”