Review
Mechanistic aspects of electrospray ionization

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Abstract

Electrospray ionization (ESI) mass spectrometry can be divided into three steps: Nebulization of a sample solution into electrically charged droplets, liberation of ions from droplets, and transportation of ions from the atmospheric pressure ionization source region into the vacuum and mass analyzer of the mass spectrometer. A sample solution is fed through a capillary tube and a high electric field at the tip of the tube pulls positive charge towards the liquid front. When electrostatic repulsion becomes stronger than the surface tension, a small electrically charged droplet leaves the surface and travels through the surrounding gas to the counter-electrode. Under the majority of experimental liquid chromatography–mass spectrometry and capillary electrophoresis–mass spectrometry conditions, positive charge on droplets is generated by the removal of negative charge via electrochemical discharge of negative ions against the metal wall of the spray capillary. When the ESI source is set up for the detection of negative ions, all power supplies are at reversed polarity. Removal of positive ions inside the tip of the spray capillary provides droplets depleted of positive charge. The supply of negative charge to the solution may also take place; electrons released from the spray capillary can be captured by sample molecules having a high electron affinity. Droplet size decreases and charge density at the droplet surface increases after droplet disintegration and solvent evaporation. When the electric field at the surface of a droplet has become sufficiently high, ions are emitted from the droplet surface into the surrounding gas and are sampled by the mass analyzer. Sample ion intensity is dependent on ion structure and is affected by solvent composition and presence of additives. ESI behaves as a concentration sensitive detector for chromatography. When the sample concentration is increased above 10 μM, the sample ion signal saturates, which can be explained by the assumption that the surface of ion-emitting droplets is full at 10 μM. Sample ion abundance over a wide m/z range is further affected by inherently mass-dependent efficiencies of ion transportation, ion separation and ion detection.

Introduction

Electrospray ionization (ESI) has become one of the most important ionization techniques for the on-line coupling of liquid phase separation methods with mass spectrometry (MS). It is a simple and elegant method that handles small and big molecules, operates at atmospheric pressure and at a moderate temperature, and is probably the most gentle ionization technique available for MS.

During the history of development of liquid chromatography (LC)–MS coupling, emphasis was put on the different designs of interface between the liquid chromatograph and the ionization technique [1]. For example, the moving belt and particle beam systems are interfaces between the LC and the electron impact and chemical ionization sources. Direct liquid introduction is an interface for a chemical ionization source. The thermospray nebulizer is an interface for electron beam- or electric discharge-induced chemical ionization. The heated pneumatic nebulizer is the interface for LC–MS with atmospheric pressure chemical ionization.

Three LC–MS techniques can be considered as ionization techniques where the “interface” is an integral part of the system: Filament-off thermospray, continuous flow fast atom bombardment (FAB) or secondary-ion mass spectrometry (SIMS), and electrospray. Continuous flow matrix assisted laser desorption ionization (MALDI) may become the fourth LC–MS technique of this kind [2].

ESI–MS can be divided into three steps: Nebulization of a sample solution into electrically charged droplets, liberation of ions from droplets, and transportation of ions from the atmospheric pressure ionization source region into the vacuum and mass analyzer of the mass spectrometer.

Section snippets

Nebulization

A detailed study of the formation of a mist of fine droplets through the exposure of a liquid to a high electric field was published by Zeleny [3]. Different shapes of sprays at various spray voltages were documented by high speed photography. Renewed scientific interest in electrospray resulted in a series of publications starting in 1952 4, 5, 6. The theory and applications of electrospray nebulization have been summarized in books 7, 8and in a special issue of the Journal of Aerosol Science

Droplet charging

Fig. 1 is laid out for the formation of positively charged droplets. From a macroscopic viewpoint, it is sufficient to assume excess positive charge to be present in the liquid front. From a chemical viewpoint, it is necessary to define the mechanism of charged droplet formation and its relationship to the composition of the sample solution, which is, in turn, strongly dependent on the composition of the eluent used for the high-performance liquid chromatographic separation.

Does positive charge

Droplet disintegration

When droplets separate from the liquid front at the tip of the spray capillary, electric repulsion has become larger than the cohesive force that keeps the liquid together. During its flight through gas at atmospheric pressure, the droplet undergoes size reduction by evaporation of solvent, so that charge density at the droplet surface increases. Furthermore, the droplets are subjected to shear forces by their flight through dense gas. As a result of both effects, droplets undergo deformation,

Ion emission from droplets

When the electric field at the surface of a droplet has become sufficiently high, ions may be emitted from the droplet surface into the surrounding gas [34]. This process has been investigated by Iribarne et al. 35, 36, 37and was called ion evaporation. Alternatively, an ion with one or more solvation shells may separate from the droplet surface as a nanodroplet [38]that loses its solvent molecules during its flight through the atmospheric pressure ionization source. Either process leads to

Sample ion signal saturation

Sample ion signal in ESI saturates at a sample concentration of approximately 10 μM, as shown in Fig. 4. At sample concentrations above 10−4 M, the ion signal decreases. Sample ion signal saturation might be attributed to insufficient charge on droplets. In the case of a single component system, made up from tetrabutylammonium bromide in a number of different solvents, it has been shown that the quaternary ammonium signal saturates at approx. 10 μM, while the spray current (droplet charge)

Sample ion formation for electrospray

Since ESI–MS makes use of sample ions present in solution, the question is how to turn a sample into sample ions in solution. A number of compounds exist as ions in solution, e.g. quaternary ammonium salts, phosphonium salts and salts of strong acids such as phosphates, sulfates and sulfonates, to name a few. For other compounds, it may be sufficient to adjust the pH in order to protonate a base or deprotonate an acid, respectively. Acids can be used for the ionization of amines, including

Concentration-sensitive behaviour of electrospray ionization

The sample ion signal in an electron impact (EI), chemical ionization (CI) or thermospray mass spectrometer is proportional to the number of sample molecules introduced into the source per unit time. In other words, MS is a mass-flow-sensitive detector for chromatography. Electrospray is very different in this respect, since the sample ion signal is proportional to sample concentration, but largely independent from the flow-rate used for sample introduction. ESI acts or behaves as a

Ion abundance throughout a spectrum

The number of ions arriving at the detector of an ESI–MS system is dependent on ESI efficiency, ion sampling efficiency into the vacuum, and ion transmission efficiency through ion optics and the mass analyzer. Ion sampling and ion transmission are mass-dependent. Ion sampling efficiency decreases for low mass ions [59]. Ion transmission through ion optics also suffers from roll-off towards low mass, and tuning may be mass-dependent.

Since the pressure inside the ion optics stage is so high that

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