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Acoustic Ejection/Full-Scan Mass Spectrometry Analysis for High-Throughput Compound Quality Control
SLAS Technology: Translating Life Sciences Innovation ( IF 2.7 ) Pub Date : 2020-11-16 , DOI: 10.1177/2472630320967625
Jun Zhang 1 , Yong Zhang 1 , Chang Liu 2 , Tom Covey 2 , Julia Nielsen 3 , Shu Li 1 , Harold Weller 1 , Wilson Shou 1
Affiliation  

High-throughput analysis of compound dissolved in DMSO and arrayed in multiwell plates for quality control (QC) purposes has widespread utility in drug discovery, ranging from the QC of assay-ready plates dispatched by compound management, to compound integrity check in the screening collection, to reaction monitoring of chemical syntheses in microtiter plates. Due to the large number of samples (thousands per batch) involved, these workflows can put a significant burden on the liquid chromatography–mass spectrometry (LC-MS) platform typically used. To achieve the required speed of seconds per sample, several chromatography-free MS approaches have previously been used with mixed results. In this study, we demonstrated the feasibility of acoustic ejection–mass spectrometry (AE-MS) in full-scan mode for high-throughput compound QC in miniaturized formats, featuring direct, contactless liquid sampling, minimal sample consumption, and ultrafast analytical speed. The sample consumption and analysis time by AE-MS represent, respectively, a 1000-fold and 30-fold reduction compared with LC-MS. In qualitative QC, AE-MS generated comparable results to conventional LC-MS in identifying the presence and absence of expected compounds. AE-MS also demonstrated its utility in relative quantifications of the same compound in serial dilution plates, or substrate in chemical synthesis. To facilitate the processing of a large amount of data generated by AE-MS, we have developed a data processing platform using commercially available tools. The platform demonstrated fast and straightforward data extraction, reviewing, and reporting, thus eliminating the need for the development of custom data processing tools. The overall AE-MS workflow has effectively eliminated the analytical bottleneck in the high-throughput compound QC work stream.



中文翻译:

用于高通量化合物质量控制的声射出/全扫描质谱分析

对溶解在 DMSO 中并排列在多孔板中用于质量控制 (QC) 目的的化合物的高通量分析在药物发现中具有广泛的用途,从化合物管理部门派遣的分析就绪板的 QC,到筛选集合中的化合物完整性检查, 用于微量滴定板中化学合成的反应监测。由于涉及大量样品(每批次数千个),这些工作流程会给通常使用的液相色谱-质谱 (LC-MS) 平台带来重大负担。为了达到每个样品所需的秒级速度,以前曾使用过几种无色谱质谱方法,但结果不一。在这项研究中,我们证明了声射质谱 (AE-MS) 在全扫描模式下用于小型化高通量化合物 QC 的可行性,具有直接、非接触式液体采样、最少的样品消耗和超快的分析速度。与 LC-MS 相比,AE-MS 的样品消耗和分析时间分别减少了 1000 倍和 30 倍。在定性 QC 中,AE-MS 在确定预期化合物的存在与否方面产生了与传统 LC-MS 相当的结果。AE-MS 还证明了其在连续稀释板中相同化合物或化学合成中的底物的相对定量中的实用性。为了便于处理 AE-MS 生成的大量数据,我们使用商用工具开发了一个数据处理平台。该平台展示了快速而直接的数据提取、审查和报告,因此无需开发自定义数据处理工具。整个 AE-MS 工作流程有效地消除了高通量化合物 QC 工作流程中的分析瓶颈。

更新日期:2020-11-16
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