John B. Fenn
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Professor
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Education
B.S., Berea College
Ph.D., Yale University
Research interests
Mass spectrometry is the art of “weighing” individual atoms and molecules to determine their masses or molecular weights. Such mass or weight information is sometimes sufficient, frequently necessary and always useful in determining the identity of a species. To practice this art one puts charge on the molecules of interest, i.e., the analyte, then measures how the trajectories of the resulting ions respond in vacuum to various combinations of electric and magnetic fields. Clearly the sine qua non of such a method is the conversion of neutral analyte molecules into ions. For small and simple species the ionization is readily carried by gas-phase encounters between the neutral molecules and electrons, photons or other ions. In recent years the efforts of many investigators have led to new techniques for producing ions of species too large and complex to be vaporized without substantial, even catastrophic, decomposition. We have been working with one of the most successful of these new techniques known as Electrospray Ionization or ESI, which in conjunction with mass analysis is often referred to as Electrospray Mass Spectrometry or ESMS.
ESI
ESI consists in flowing a few microliters a minute of dilute analyte solution through a small tube or “needle” on the axis of a chamber containing a bath gas such as dry nitrogen. A potential difference of several kilovolts between the needle and the chamber walls produces an intense electric field at the needle exit that disperses the emerging liquid into a fine spray of charged droplets. Driven by the field each droplet drifts toward the end wall of the chamber where a small aperture leads into a vacuum system housing a mass spectrometer. Solvent evaporation shrinks the droplet thus increasing its surface charge density and, therefore, the intensity of its surface field. Ultimately that field becomes strong enough to “lift” ionic species from the droplet to form free ions in the bath gas. Some of the resulting dispersion of ions in bath gas passes through the aperture into the vacuum system for mass analysis. ESI can readily ionize very large and complex species such as peptides, proteins, nucleic acids and carbohydrates that play a vital role in living systems. Moreover, the ions formed from large (and “heavy”) molecules have so many charges that their mass/charge ratio is seldom greater than about 2000. Thus they can be weighed by relatively inexpensive analyzers. Even a simple quadrupole mass filter can readily provide values of molecular weight up to several tens of thousands with an accuracy of one part in 40,000. In recent experiments individual ES ions have been formed with molecular weights in the millions, each carrying five thousand or more elementary charges.
Although ESI is now in daily use all over the world, its component processes and mechanisms, especially the dispersion of the sample liquid into charged droplets, and the formation of gas phase ions from those droplets are poorly understood. Both of these processes are very complex, depending strongly on an intricate interplay between variables such as flow rate, applied field and solution properties including conductivity, surface tension concentration, dielectric constant and viscosity, as well as the structure and confirmation of the analyte molecules. We have great fun in trying to sort out and understand the roles of these variables with an eye toward the practical goals of improving the analytical sensitivity of the method along with our ability to interpret the information it provides in such abundance.
Publications
Nguyen, S.; Fenn, J.B., Gas-phase ions of solute species from charged droplets of solutions. Proceedings of The National Academy of Sciences of The United States of America 2007, 104, 1111-1117.
Kessick, R.; Fenn, J.; Tepper, G., The use of AC potentials in electrospraying and electrospinning processes. Polymer 2004, 45, 2981-2984.
Fenn, J.B., Electrospray wings for molecular elephants (Nobel lecture). Angewandte Chemie-International Edition 2003, 42, 3871-3894.
Zhan, D.L.; Fenn, J.B., Gas phase hydration of electrospray ions from small peptides. International Journal of Mass Spectrometry 2002, 219, 1-10.
