Michael P. Balogh

As a related aside to this topic, you might read an earlier column (1), which describes the non-liquid chromatography (LC) ionization methods publicized in recent years: desorptive electrospray (DESI) and direct analysis real time (DART). Also, from http://www.CoSMoScience.org/, you can download a PDF version of Charles McEwen's (DuPont, Wilmington, Delaware) excellent presentation, which he delivered at this year's Conference on Small Molecule Science at San Diego. That presentation focuses on gas chromatography (GC) ionization that was developed without significantly modifying existing ESI sources. Of special interest is McEwen's comparison between APCI as the ionization mechanism and APPI. Briefly, a reduced vapor load and lamp energy combine to make both a sensitive and specific ionization technique — as sensitive as APCI but with less noise. The work also serves as a cautionary tale depicting how ions created from the same analytes can look quite different depending upon the ionization technique you use.

Practical and theoretical knowledge culled over the last decade of developing and applying atmospheric ionization techniques teaches us some lessons. Liquid, while a necessary intermediary in separating and transporting analytes and creating ions, is also a vestigial remnant of the condensed-phase LC process. To paraphrase from McEwen's presentation (2), solvent in the gas phase limits ionization to molecules that are more basic than the solvent (except in APPI, which is not acid–base but nonetheless solvent-mediated). Therefore, removing solvent and water vapor from the ionization region increases the number of compounds ionizable by the most convenient methods performed at atmosphere.

Work performed in the early 1990s only recently has yielded a more unified understanding of the mechanisms involved in ion production. The transfer mechanism of potential from liquid to analyte, which creates ions, had been a topic of controversy. Richard Cole's article in 2000 is still one of the better examinations of the two most popular theories (3). The charge residue mechanism, first proposed by Dole in 1968 (4), theorizes a chain of events where, as droplets evaporate, the surface tension on each ultimately cannot oppose the repulsive forces from the imposed charge, and each droplet explodes into many smaller droplets. These coulombic fissions occur until droplets containing a single analyte ion remain. A gas-phase ion forms when solvent from the last droplet evaporates.

Iribarne and Thomson (5) proposed the ion evaporation mechanism in 1976 as an alternative model. In this theory too, small droplets are formed by coulombic fission. However, the electric field strength at the surface of the droplet is thought to be high enough to make it energetically favorable for solvated ions to leave the droplet surface and transfer directly into the gas phase. It is possible, as Cole argues, that the two mechanisms actually might work in concert. The charge residue mechanism dominates for masses higher than 3000 Da; the ion evaporation dominates for lower masses.

As practitioners, we have come to accept that ESI works. But understanding how ions are liberated from our liquid mobile phase in the gas-phase transition will help us understand and diagnose issues such as lack of expected sensitivity and ion suppression. The ESI probe, or device, is typically a conductive capillary, usually made of stainless steel, through which the solvated analyte flows. The capillary, contained within a larger-bore cylinder, allows a concentric nitrogen flow applied to the aerosol at its exit point. The added shear forces of the gas and heat transmitted from adjacent supplemental devices, or direct heating of the gas itself, enhances formation of aerosol droplets. The solvent leaves the ESI probe carrying a net ionic charge.