(501g) Mass Spectrometry of Biomolecules Using AC Electrospray Ionization

Since John Fenn's pioneering work on proteomic mass spectrometry, electrospray ionization (ESI) has become a popular ?soft? ionization technique for the ionization of large biomolecules such as proteins without fragmenting them. This method utilizes a sufficiently high electric field to deform the liquid source into a so-called Taylor cone, and a charged liquid jet emerges from the tip of the cone. This jet further undergoes Rayleigh fission to produce sub-micron droplets that further cascade into next generation of charged drops and eventually lead to the molecular ion of the species that is suitable for detection by mass spectrometry.

In the present work, we demonstrate the implementation of a high frequency AC electrospray as an ionization technique for mass spectrometry. Unlike the familiar DC Taylor cone that has a steady half cone angle of ~ 49^o , an AC cone has a much sharper tip, with a half cone angle ~ 11^o and shows a continuous temporal growth. In our earlier work, we have shown that the application of a suitable high frequency AC electric field, where the period of the AC signal ω^-1 is less than the Maxwell relaxation time scale of the liquid jet ( σ and ε are the conductivity and permittivity of liquid, respectively), preferentially entrains low mobility ions towards the tip of the cone. The Coulombic repulsion between these ions leads to the formation of a slender ac cone and is responsible for its continuous axial growth. Hence, whenever the anions are the low mobility ions, AC electrospray serves to generate an efficient ionization means for negative mode mass spectrometry. This is in direct contrast to its DC counterpart, which tends to undergo electron discharge in negative mode and often requires the use of electron scavenger gases such as oxygen and SF₆ to capture the excessive electrons. Moreover, the charge per unit volume within the droplets ejected by an AC electrospray is shown to be an order of magnitude less than that of a DC electrospray, which goes on to suggest that an AC electrospray may serve as a ?softer? ionization technique. Here, we present results from negative mode mass spectrometry on AC electrospray of solvents, oligonucleotides and neuropeptides and provide a direct comparison of this novel ionization technique with DC electrospray Ionization.