Terry Lee, Ph.D. Research

Mass Spectrometry of Biomolecules
With the advent of new ionization methods, such as electrospray and matrix assisted laser desorption (MALDI), it is now possible to produce gas phase ions of almost any size and class of molecular compounds. A major part of our work is to develop new technologies to bridge the gap that exists between the inherent sensitivity of mass spectral analysis and its application to "real life" biological problems. More often than not, compounds of interest are present in vanishingly small amounts as part of complex mixtures. Additionally, there are often components in the mixture that interfere with the mass spectral analysis.
The technological improvements that we have developed include innovative instrumentation and novel methods of data acquisition and analysis. The sensitivity of our LC/MS technology has been greatly improved by the creation of a micro-electrospray (microspray) interface. The output from a normal electrospray source far exceeds the pumping capacity of a mass spectrometer vacuum system. Consequently, a major portion of the sample does not make it into the instrument. With the microspray interface, all of the sample is analyzed, greatly reducing the sample amount needed to obtain quality MS data.
With the feasibility of very low flow electrospray demonstrated, future work will be centered on the construction of silicon chip devices that incorporate the electrospray source and separation device as a single disposable integral unit. These devices will be micromachined using the same technology used to manufacture computer chips. The result will be a universal, low-cost, disposable sample preparation device for mass spectrometers. The efficiency of mass spectral analyses can be vastly improved in both time and sample amount by using expert systems to analyze incoming data and make real time decisions in analysis parameters. In the context of an LC/MS run, all of the required information to solve a given problem can be acquired in a single analysis.
This methodology will make it possible to more easily transfer the expertise needed to solve particular analytical problems without the need for extensive training of the individual actually doing the analysis. The net effect will be to make mass spectrometry a more useful tool for solving biomedical problems.