Desorption/ionization on silicon (DIOS) is a soft laser desorption method used to generate gas-phase ions for mass spectrometry. It is a matrix-free technique in which a sample is deposited on porous silicon and desorbed from the silicon surface by a laser. DIOS can be used to analyze organic molecules, biomolecules and peptides, and to image cells. Desorption/ionization on silicon (DIOS) is a soft laser desorption method used to generate gas-phase ions for mass spectrometry. It is a matrix-free technique in which a sample is deposited on porous silicon and desorbed from the silicon surface by a laser. DIOS can be used to analyze organic molecules, biomolecules and peptides, and to image cells. Soft laser desorption is a soft ionization technique. It ionizes molecules with minimal fragmentation. This is useful for larger molecules and molecules that fragment easily. The first soft laser desorption technique was Matrix-assisted laser desorption/ionization (MALDI). In MALDI, the analyte is first mixed with a matrix solution. The matrix absorbs energy from the laser pulse and transfers it to the analyte, causing desorption and ionization of the sample. MALDI generates + ions. DIOS was first reported by Gary Siuzdak, Jing Wei and Jillian M. Buriak in 1999. It was developed as a matrix free alternative to MALDI for smaller molecules. Because MALDI uses a matrix, background ions are introduced due to ionization of the matrix. These ions reduce the usefulness of MALDI for small molecules. In contrast, DIOS uses a porous silicon surface to trap the analyte. This surface is not ionized by the laser, allowing for the analysis of small molecules. DIOS has been shown to detect peptides, natural products, small organic molecules, and polymers with little fragmentation. DIOS can be used for proteomics. It has been reported as a useful method protein identification. Because it is matrix free, it can be used to identify smaller biomolecules than MALDI. In addition, it can be used to monitor reactions on a single surface through repeated MS analyses. Reaction monitoring can be used to screen enzyme inhibitors. Atmospheric pressure DIOS was shown to be an effective tool for quantitative analysis of drugs with high proton affinity. The use of DIOS to image small molecules has been demonstrated. Lin He and coworkers imaged small molecules on mouse liver cells. They also used marker molecules to image HEK 293 cancer cells.