Traditional mass spectrometry used harsh electron beams that shattered delicate biological proteins into unrecognizable debris; John Fenn used an electrified mist to gently levitate giant biomolecules intact into the vacuum chamber. By generating multiply charged ions from liquid droplets, Electrospray Ionization enabled precision mass spectrometry of entire intact proteins and founded modern proteomics.

For decades, analytical chemistry had perfected scales to weigh small chemical molecules with single-atom precision, but the giant protein machines that drive human health and disease remained completely unmeasurable. Blasting proteins with high heat or electron beams shredded them into useless microscopic dust.
John Fenn achieved what he called "giving wings to molecular elephants." By spraying a liquid solution of proteins from an electrified needle, the charged droplets evaporate gently, leaving massive intact proteins floating in a vacuum chamber without a single broken molecular bond.
Electrospray mass spectrometry became the bedrock of modern biopharmaceuticals and cancer proteomics. By identifying disease biomarkers from a single drop of blood, by ensuring the purity of monoclonal antibody therapies, and by mapping the complete human proteome, soft ionization mass spectrometry transformed clinical science.
Electrospray Ionization for Mass Spectrometry of Large Biomolecules
Electrospray ionization has recently emerged as a powerful technique for producing intact ions in vacuo from large and complex species in solution. To an extent greater than has previously been possible with the more familiar "soft" ionization methods, this technique makes the power and elegance of mass spectrometric analysis applicable to the large and fragile polar molecules that play such vital roles in biological systems. The distinguishing features of electrospray spectra for large molecules are coherent sequences of peaks whose component ions are multiply charged, the ions of each peak differing by one charge from those of adjacent neighbors in the sequence. Spectra have been obtained for biopolymers including oligonucleotides and proteins, the latter having molecular weights up to 130,000, with as yet no evidence of an upper limit.
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