Small molecule analysis using laser desorption/ionization mass spectrometry on nano-coated silicon with self-assembled monolayers

► A new substrate using controllable nano-structured silicon surfaces based on the self-assembly of silane molecules (OTS and TPDA) was proposed. ► A matrix-free approach for use in laser desorption/ionization mass spectrometry (LDI-MS) for the analysis of small target molecules was demonstrated. ► The modified surfaces with nano-overlayers should be seriously considered to improve LDI-MS analysis. ► The detection of small molecules by eliminating the need for matrix provides a number of important advantages.