Electrospray ionization
ESI is different from other ionization processes (e.g. matrix-assisted laser desorption/ionization, MALDI) since it may produce multiple-charged ions, effectively extending the mass range of the analyser to accommodate the kDa-MDa orders of magnitude observed in proteins and their associated polypeptide fragments.
The electrospray ionization technique was first reported by Masamichi Yamashita and John Fenn in 1984,[3] and independently by Lidia Gall and co-workers in Soviet Union, also in 1984.
[4] The development of electrospray ionization for the analysis of biological macromolecules[5] was rewarded with the attribution of the Nobel Prize in Chemistry to John Bennett Fenn and Koichi Tanaka in 2002.
In 1914, John Zeleny published work on the behaviour of fluid droplets at the end of glass capillaries and presented evidence for different electrospray modes.
[13][14] John Bennett Fenn was awarded the 2002 Nobel Prize in Chemistry for the development of electrospray ionization mass spectrometry in the late 1980s.
To decrease the initial droplet size, compounds that increase the conductivity (e.g. acetic acid) are customarily added to the solution.
Large-flow electrosprays can benefit from nebulization of a heated inert gas such as nitrogen or carbon dioxide in addition to the high temperature of the ESI source.
[19] The aerosol is sampled into the first vacuum stage of a mass spectrometer through a capillary carrying a potential difference of approximately 3000 V, which can be heated to aid further solvent evaporation from the charged droplets.
[13] The gas-phase ions form after the remaining solvent molecules evaporate, leaving the analyte with the charges that the droplet carried.
[32] The efficiency of generating the gas phase ions for small molecules in ESI varies depending on the compound structure, the solvent used and instrumental parameters.
The electrosprays operated at low flow rates generate much smaller initial droplets, which ensure improved ionization efficiency.
In 1993 Gale and Richard D. Smith reported significant sensitivity increases could be achieved using lower flow rates, and down to 200 nL/min.
Although there may not be a well-defined flow rate range for electrospray, microspray, and nano-electrospray,[40] studied "changes in analyte partition during droplet fission prior to ion release".
[44] Applications of this method include the analysis of fragile molecules and guest-host interactions that cannot be studied using regular electrospray ionization.
The laser desorbs or ablates material from the sample which is ejected from the surface and into the electrospray which produces highly charged ions.
Electrostatic spray ionization (ESTASI) involved the analysis of samples located on a flat or porous surface, or inside a microchannel.
[55][56][57] Electrospray ionization is the ion source of choice to couple liquid chromatography with mass spectrometry (LC-MS).
The analysis can be performed online, by feeding the liquid eluting from the LC column directly to an electrospray, or offline, by collecting fractions to be later analyzed in a classical nanoelectrospray-mass spectrometry setup.
Capillary electrophoresis-mass spectrometry was enabled by an ESI interface that was developed and patented by Richard D. Smith and coworkers at Pacific Northwest National Laboratory, and shown to have broad utility for the analysis of very small biological and chemical compound mixtures, and even extending to a single biological cell.
