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Sir John Bennett Fenn won a Nobel prize for electrospray ionization. The first use of electrospray ionization with mass spectrometry was by Malcolm Dole in 1968.

By applying a high voltage to a liquid to make an aerosol, the electrospray ionization technique (ESI) is used in mass spectrometry to produce ions. Because it overcomes macromolecules' tendency to fragment when ionized, it is particularly helpful in creating ions from macromolecules.

Electrospray ionization mass spectrometry (ESI-MS) or, less frequently, electrospray mass spectrometry are the terms used to describe ESI-based mass spectrometry (ES-MS). ESI is referred to as a "soft ionization" approach because there is hardly any fragmentation.

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