My research involves development of mass spectrometric instrumentation for the analysis of large biopolymers. Mass spectrometry is the current state of the art for high throughput analysis of proteins such as that required in the field of proteomics, but current commercial mass spectrometers are severely limited in their ability to analyze large molecules such as intact proteins. For this reason, proteomics researchers have resorted to techniques such as enzymatic digestion to break down the proteins of interest into smaller peptides which are more readily analyzed by their mass spectrometers. However, enzymatic digestion has the unfortunate side effect of complicating an already complex mixture of compounds leading to mass spectra which are cluttered and difficult to interpret. This has forced proteomics researchers to use costly and time consuming separation steps prior to mass spectrometric analysis in order to yield usable data. This problem can be largely attributed to increased ion beam divergence, detector saturation as well as decreased detector efficiency at high m/z. To combat this problem, the Smith group is developing detectors that will mitigate or eliminate these effects such as inductive charge detectors, Faraday cup detectors and nanoelectro-mechanical devices.
A second focus of my research involves improving the sensitivity of mass spectrometry. Our estimates indicate that, for the ESI-ToF instrument in our laboratory, only about 1 in 1012 analyte molecules that emerge from the spray tip are actually detected. This is an alarmingly low number! The Smith group is exploring several methods of improving this in addition to the development of more sensitive detectors. We are developing single droplet ion sources as a method of overcoming spray losses. We are also looking to employ aerodynamic lenses for the collection and focusing of electrospray generated ions. We are also attempting to recharge single droplets after electrospray as a method of overcoming the problem of signal suppression by preferential charging of certain analytes. With these advances we feel that it may be possible to perform single molecule mass spectrometry.
GSTP Training Program
425 Henry Mall, Room 3445
Madison, WI 53706