Large ions: From water droplets to pyruvate kinase

Mass spectrometry has been a highly influential technique over the past century in a wide range of disciplines, especially in biological applications. Despite major developments and improvements over the years, there is still a practical upper size limitation associated with current instrumentation arising both from design limitations and difficulties associated with deconvoluting spectra cluttered with overlapping charge state signals. We have developed a novel charge detection mass spectrometer that addresses these size limitations and pushes the upper limits of mass spectrometry to new extremes. These systems have been used to study the physics of micron-sized, charged water droplets generated from an electrospray source. Water droplets and charge separation associated with those droplets is important to the understanding of a range of topics including thunderstorm electrification and the waterfall effect, and insight into fission of these water droplets could have important implications about electrospray sources that are commonly used for biological and clinical mass spectrometry.;In the interest of developing new analytical targets for our charge detection instrumentation, large protein complexes have been studied using high resolution ion mobility mass spectrometry. Our focus initially has been on rabbit muscle pyruvate kinase. This is an enzymatic complex that functions in the last step of the glycolysis cycle, a very important metabolic pathway. The analysis of this protein complex has yielded the unexpected discovery of multiple stable structures present in the gas phase, which merits further investigation with regards to the interpretation of their origin.