Objective

The Acoustic Mist Ionization Mass Spectrometer (AMI-MS) is a novel combination of two existing technologies; Acoustic Droplet Ejection (ADE) and Time of Flight (ToF) Mass Spectrometry (MS) to achieve high-throughput MS analysis from 384-well plates. The hyphenation of these two technologies enables sampling into the MS at a rate of 3 samples per second, a full 384 well plate can be read in under 2 minutes. To achieve this high-throughput it has been necessary to remove the slow separative chromatography step of a traditional LCMS system. While enabling speed, the loss of chromatography presents other issues such as problems of suppression as some of the reagents required to support biology “steal” charge from the analytes of interest. This is a particular problem for kinases which require metal cations to support enzyme activity. For a model kinase system, we will present the approaches we have used to develop assays with optimised buffers compatible with AMI-MS and a comparative screening data from both AMI-MS and a traditional detection technology (Promega ADP Glo). To date AMI-MS technology has been used to screen multiple HTS targets within AstraZeneca, however, this is the first example of the application of AMI-MS to screen a kinase target.