The objective of this project is to develop microfabricated devices for the comprehensive of cellular proteins to normal, precancerous and cancerous tissues. Specifically, we propose to develop lab-on-a-chip technologies as an alternative to the slow and labor-intensive two dimensional (2D) gel methods currently used for comprehensive protein analysis. The microchips will integrate on a single structure elements that enable multidimensional separations of protein mixtures, with either on-chip labeling for fluorescence detection or electrospray ionization (ESI) of the analytes for direct, on line interfacing with mass spectrometry (MS). Successful completion of the project will result in high throughput, automated devices for use in identifying disease markers and elucidating the molecular basis of cellular transformation. These devices will have research applications for understanding cellular transitions from normal to diseased states. In addition, these research tools will also find application in clinical diagnosis and therapy development.