Proteomics is an emerging field that holds great promise for many areas of biomedical research, including cellular and molecular biology, clinical diagnostics, and drug discovery and testing.  Modern two-dimensional gel electrophoresis  (2DE) and mass spectrometry (MS) have provided enabling technology for proteomics.  However, this initial enabling technology is far from ideal, and many improvements are needed for its full potential to be realized.  The greatest limitations of the current technology are a lack of sensitivity, or inability to detect proteins of low relative abundance, and low sample throughput.  These limitations have greatly hampered the application of proteomics to the elucidation of cell signaling pathways and the elucidation of the mechanisms that cause disease.  Currently, most proteins that have been identified as markers are housekeeping or structural proteins.  These proteins can be removed from the signal transduction events by many levels and are therefore less reliable as markers.  The lack of sensitivity of current 2DE-based technology is caused primarily by a lack of separating or resolving power as the high abundance proteins mask the identification of low abundance proteins.

The long-range goal of this project is to develop the next generation of proteomics instrumentation and apply the technology to the study of disease.  The complexity of living systems and their proteomes is daunting, and therefore our focus will be to increase sensitivity, throughput, and information content.  As a step towards the long-range goal, the objective is to develop and characterize a microfluidic system that will provide both the crucial link between more high efficiency multi-dimensional column separations and analysis by mass spectrometry.  The rationale for this work is that proteomics is central to the study of disease and currently the field is instrumentally limited.  Therefore, instrumentation that can delve deeper into a cell’s proteome is sorely needed.  Proteomics is fundamental to our understanding of how normal cells function and the mechanisms through which aberrant cells escape normal control.