Today we going to talk about electrospray ionization. Electrospray ionization commonly referred to as ESI is an example of an atmospheric pressure ionization technique. Other examples include atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo-ionization (APPI). ESI for LC-MS in its current form was formally proposed by John Fenn and his coworker, Masamichi Yamashita in the early 1980s. But processes very similar to ESI were observed and reported as far back as 1914 and even earlier. In an ESI ion source, a narrow metal capillary is held at high voltage and a potential difference is produced between the capillary and the orifice of the mass spectrometer.
Fundamentals of Mass Spectrometry
A solution containing analyte ions, often an LC eluant, is sprayed from the capillary. Usually, a flow of gas is also employed to more efficiently nebulize, or break up, the liquid stream into tiny droplets. ESI requires the formation of ions in solution prior to the transfer of the gas phase. Typically, molecules are believed to undergo electrochemical reactions, either from redox reactions at the liquid metal interface of the capillary tip or through acid-base reactions in solution. The exact mechanism by which ions are transferred in the gas phase is still a matter for debate and ongoing research. But two main processes have been proposed.
1) The ion evaporation mechanism (IEM), where the electric field of the surface of highly charged small droplets becomes sufficient to field desorbed ions directly from the surface. In this process, solvated ions leave the larger droplet sequentially and the droplet shrinks until just dissolved ions remain.
2) For the charge residue module (CRM), where ions eventually become de-solvated as solvent molecules leave the droplet surface. In this process, solvent molecules evaporate from the larger droplet and the droplet shrinks until just de-solvated ions remain.
Evidence suggests that smaller ions are more likely to enter the gas phase by the IEM, whereas larger multiple charged species are more likely to follow the CRM. Modifications or related processes to these two mechanisms have also been proposed. In contrast to vacuum ionization techniques, such as Electron Ionization, or EI as it’s usually known, ESI is considered to be a soft ionization technique. This is because ESI typically produces intact ions related to the analyte molecule and fewer fragment ions than vacuum ionization techniques.
In EI to form positive ions, high energy electrons impact with the analyte molecules, knocking an electron from the outer shell of the molecule and typically imparting enough energy to break up the molecular ion to produce fragment ions. In ESI, to form positive ions, cations, for example, hydrogen ions often just called protons to interact with the analyte molecules and form new bonds between the cations and the analyte molecules. This produces adductions, also sometimes called cationized molecules, with a total mass equal to the mass of the analyte molecule plus the mass of the cation. It is also possible to form negative ions in ESI by forming adduct ions of anions, such as chloride ions. Negative ions in the ESI can also be formed by other processes, such as proton abstraction, in which a proton is removed from an analyte molecule to leave a negatively charged ion. You can learn more about these processes in the video covering adduct formation. For background reading and further information about ESI, you could take a look at these references.