In recent years, mass spectrometry techniques such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) have made a substantial impact on molecular biology. These tools allow detailed chemical information to be obtained on large structures at levels of sensitivity previously known only for more crude techniques such as gel electrophoresis with radiolabeled compounds. A new and inexpensive modification of MALDI has been discovered which eliminates the added matrix material that both allows MALDI to occur and limits its applicability. The new method, called laser desorption/ionization on porous silicon (DIOS), depends on the properties of chemically derivatized porous silicon to trap analyte molecules and provide an efficient mechanism for their ejection into the gas phase as intact and detectable ions upon pulsed laser irradiation. Because no added matrix is used, small molecules of molecular weight as low as 80 Daltons can be detected with high sensitivity by direct laser desorption without interference. The goals of this program are: (1) to further refine the DIOS technique, (2) to characterize porous silicon surfaces that are active in DIOS-MS and thus gain insights into the mechanisms of desorption and ionization, (3) to modify DIOS surfaces to allow a variety of chemical and biochemical reactions to be conveniently monitored by mass spectrometry, and (4) to develop porous silicon materials that both support DIOS and allow for chromatographic separation of molecules. As tests of the analytical technique, we will investigate the screening of chemical and enzymatic catalysts on DIOS-MS plates, on-plate affinity labeling, on-plate digestion and identification of proteins, and de novo sequencing using DIOS post-source decay MS. The ability to tailor surface properties by varying the conditions of preparation and modification of porous silicon, coupled with the routine use of surface science probes to examine what we make, will enable us to bring this technique to the level required for broad use by the chemistry and biochemistry communities.
