High-Throughput Screening of Small Molecule Libraries using SAMDI Mass Spectrometry

[Image: see text] High-throughput screening is a common strategy used to identify compounds that modulate biochemical activities, but many approaches depend on cumbersome fluorescent reporters or antibodies and often produce false-positive hits. The development of “label-free” assays addresses many of these limitations, but current approaches still lack the throughput needed for applications in drug discovery. This paper describes a high-throughput, label-free assay that combines self-assembled monolayers with mass spectrometry, in a technique called SAMDI, as a tool for screening libraries of 100 000 compounds in one day. This method is fast, has high discrimination, and is amenable to a broad range of chemical and biological applications.