Acoustic mist ionization platform for direct and contactless ultra-high-throughput MS analysis of liquid samples

Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discov-ery. However, current methods of liquid sample introduction to a detector are slow and limit the use of mass spectrometry for kinetic and high-throughput applications. We present the development of an acoustic mist ionisation (AMI) interface capable of contactless nanolitre-scale “infusion” of up to 3 individual samples per second into the mass detector. Installing simple plate handling automation allowed us to reach a throughput of 100,000 samples per day on a single mass spectrome-ter. We applied AMI-MS to identify inhibitors of a human histone deacetylase from the AstraZeneca’s collection of 2 mil-lion small molecules and measured their half-maximal inhibitory concentration. The speed, sensitivity, simplicity, robustness and consumption of nanolitre volumes of sample suggest that this technology will have a major impact across many areas of basic and applied research.