Ion Hydration and Nanodrops in Mass Spectrometry

University Of California-Berkeley, Berkeley CA

Investigators

Abstract

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Evan Williams and his group at the University of California, Berkeley are investigating the chemistry and physics of charged aqueous nanodrops, with particular focus on characteristics relevant to the capabilities of electrospray ionization mass spectrometry (ESI MS), a revolutionary chemical analysis method for which John B. Fenn received the Nobel Prize in Chemistry in 2002. The Williams lab is investigating how the size and shape of ESI droplet emitters affect the initial droplet size and resulting performance of ESI MS. Charge detection mass spectrometry - a technique that is being developed in the Williams lab - is used to weigh both droplets and residues from dehydrated droplets in order to infer information about initial droplet sizes. The physics of droplet breakup from excess charge is also probed using this device, with goals of improved understanding of the ion formation process, and improved analytical performance. Computational modeling supports these efforts, providing a more detailed understanding of the physics behind these processes. The nanoscale emitters enable measurements from biochemical systems using the same types of buffers as used for measurements with other methods. Heating these emitters enables assessment of the thermal stabilities of proteins and protein complexes - information that is important in understanding phenomena such as drug-target interactions and protein therapeutics. A laser heating method that extends these measurements to aggregation-prone proteins and improves measurement speed by at least a factor of ten is being developed and could replace traditional methods that are widely used in protein chemistry and in pharmaceutical labs. Students working on this project learn important skills, including how to design rigorous experiments, to interpret data without bias, and to communicate their results to the broader community. The Williams lab is studying the chemistry and physics of charged aqueous nanodrops with diameters between ~10 nm and 1 micron formed using custom electrospray emitters. Charge detection mass spectrometry provides a means of detecting how the emitter tip diameter and taper affect the initial nanodrop sizes, and to establish conditions needed to achieve a single analyte molecule per droplet. The work seeks improved understanding of how analyte ions are formed from charged nanodrops and how anions affect cation emission. Molecular dynamics simulations of ion emission of small folded proteins are being tested through direct measurement of ion emission in trapped aqueous nanodrops below 40 nm diameter. A parallel goal is to explore emitter characteristics that improve performance of native mass spectrometry using traditional biochemical buffers containing high concentrations of nonvolatile salts. This will facilitate direct comparison of mass spectrometry data with that obtained from complementary biophysical methods using the same solutions. The effect of different matrices on protein stability, structure, and stoichiometry in solution are being investigated using resistively heated capillaries to measure thermal stabilities. A new laser-based method to make these measurements significantly faster is being developed for application to proteins that are prone to aggregation at elevated temperatures. These measurements should enhance our understanding of phenomena such as the formation of chiral-selective serine octamers in solution. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.