Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples
Acoustic Mist Ionization Platform for Direct and Contactless Ultrahigh-Throughput Mass Spectrometry Analysis of Liquid Samples
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DOI：
10.1021/acs.analchem.9b00142
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发表时间：
2019-03-19
影响因子：
7.4
通讯作者：
Wingfield, Jonathan
中科院分区：
文献类型：
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作者：
Sinclair, Ian;Bachman, Martin;Wingfield, Jonathan
质谱（MS）作为定量检测技术在药物发现中的应用具有许多优点。然而，目前将液体样品引入检测器的方法是缓慢的，并且限制了质谱法用于动力学和高通量应用。我们提出了一种声雾电离（AMI）接口的发展，能够非接触式纳升规模的“输液”高达每秒三个单独的样品到质量检测器。通过安装简单的自动化样品板处理系统，我们可以在一台质谱仪上实现每天100，000个样品的处理量。我们应用AMI-MS从阿斯利康收集的200万个小分子中鉴定出人类组蛋白去乙酰化酶的抑制剂，并测量了它们的半最大抑制浓度。速度，灵敏度，简单性，鲁棒性和纳升样品体积的消耗表明，这项技术将在基础和应用研究的许多领域产生重大影响。
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.