Electrospray ionization of a whole virus: analyzing mass, structure, and viability.

Electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) were the result of decades of research effort dedicated toward analyzing intact biomolecules. The practicality of these ionization methods fueled the explosion of mass spectrometry witnessed in the past decade. In fact, the widespread utility of ESI and MALDI led to the awarding of the 2002 Nobel prize in Chemistry to Fenn and Tanaka for their roles in developing these techniques. The focus of this article is largely on ESI, which has the unique ability to gently generate gas-phase ions directly from solution. Initially, the ability to transfer intact proteins and nucleic acids into the gas phase was reason enough for excitement, yet soon after it was shown that even noncovalent interactions could survive the ESI ionization/desolvation process. The first noncovalent interactions observed included a protein heme and receptor ligand complexes, multimeric enzyme inhibitor complexes, and, ultimately, whole-virus analysis was achieved.