Electrospray (Es)
Electrospray mass Spectrmetry (ESMS) was developed in the year 1989. In this technique, the sample is dissolved in a liquid with mobile phase (water: acetonitrile or water: methanol, 1:1) and is pumped (at the rate lower than microliter per-minute) through a hypodermic needle at high voltage, producing small droplets (upon a micrometer in size). These droplets rapidly evaporate and impart charge onto the analyte molecules. The ionization take place in the atmosphere and therefore is very gentle, causing no fragmentation of analyte ions in the gas phage. It is, therefore, also described as an atmospheric pressure ionization (API) technique. A stream of nitrogen gas (the nebulising gas) that flows through a tube co-axial to the main capillary helps in the spraying process.

ES produces may more ions than MALDI and these ions are transferred into mass spectrometer with high efficiency for analysis. A wide range of molecules including proteins, oligonucleotides, sugars and lipids can be analyzed by ES-MS. Electrospray is performed in different modes including the following two: the first, is the nanelectrospray, which is a miniaturized version and operates without pumps at a very low flow rates (few micrometer at the tip), and the second, is the high-performance liquid chromatography (HPLC), which may also be combined with mass spectrometry (LC-MS) so that MS analysis of components takes place on line, as they elute from chromatographic column.