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Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples

Sinclair, Ian, Bachman, Martin, Addison, Daniel, Rohman, Mattias, Murray, David C., Davies, Gareth, Mouchet, Elizabeth, Tonge, Michael E., Stearns, Richard G., Ghislain, Lucien, Datwani, Sammy S., Majlof, Lars, Hall, Eric, Jones, Gareth R., Hoyes, Emmy, Olechno, Joe, Ellson, Richard N., Barran, Perdita E., Pringle, Steven D., Morris, Michael R., Wingfield, Jonathan
Analytical chemistry 2019 v.91 no.6 pp. 3790-3794
acoustics, automation, drugs, histone deacetylase, humans, ionization, mass spectrometry, mists, spectrometers
Mass spectrometry (MS) has many advantages as a quantitative detection technology for applications within drug discovery. 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 ionization (AMI) interface capable of contactless nanoliter-scale “infusion” of up to three 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 spectrometer. We applied AMI-MS to identify inhibitors of a human histone deacetylase from AstraZeneca’s collection of 2 million small molecules and measured their half-maximal inhibitory concentration. The speed, sensitivity, simplicity, robustness, and consumption of nanoliter volumes of sample suggest that this technology will have a major impact across many areas of basic and applied research.