A typical electrospray ionization setup is shown in Figure 1-1. In ESI, a high electric field is
applied between a solution containing metal capillary and the entrance of the mass
spectrometer. The high potential (2-6 kV), in combination with a surrounding nebulizing gas,
aids in drawing the sample solution out of the small opening of the capillary, and breaks it into
charged droplets on the order of several microns in diameter.26 A heated drying gas assists in
evaporation of the solvent from the droplets, resulting in a decrease in droplet size, and an
increase in charge repulsion at the surface of the droplets. When the force of the Coulombic
repulsion equals the surface tension of the droplet, otherwise known as the Rayleigh limit, the
droplet undergoes a Coulombic explosion, or fission, producing smaller, charged daughter
droplets, which subsequently undergo further evaporation.21 Repeated events of evaporation
and fission ultimately lead to droplets of nanometer size, from which analyte molecules are
released as intact gas phase ions of the form (M+nH)n+ (in positive ion mode) or (M-nH)n- (in negative ion mode), which are drawn into the mass spectrometer by the potential and pressure
gradients.