Acoustic Sample Deposition MALDI-MS (ASD-MALDI-MS)
Acoustic Sample Deposition MALDI-MS (ASD-MALDI-MS)
复制标题
声学样品沉积 MALDI-MS (ASD-MALDI-MS)
DOI：
10.1177/2211068215594769
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
D. Drexler
中科院分区：
文献类型：
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作者：
Jefferson Chin;Elizabeth Wood;Grace S. Peters;D. Drexler
在药物发现的早期阶段，针对药物靶标的化合物库的高通量筛选（HTS）是识别潜在先导分子的常用方法。为了使这些 HTS 活动高效且成功，对化合物收集进行持续的质量控制是必要且至关重要的。然而，大量的化合物样品和有限的样品量带来了独特的挑战。这里介绍的是一种新的工艺流程的概念验证研究，用于小分子化合物库的质量控制筛选，该流程仅消耗最少量的样品并提供化合物特异性的分子数据。该过程采用声学样品沉积 (ASD) 技术进行离线样品制备，将纳升体积以阵列形式沉积到显微镜载玻片上，然后进行基质辅助激光解吸/电离质谱 (MALDI-MS) 分析。采用 ASD-MALDI-MS 工作流程对 384 种化合物阵列进行的初步研究获得了 75% 的首次通过阳性识别率，每个样品的分析时间 <1 秒。
In the early stages of drug discovery, high-throughput screening (HTS) of compound libraries against pharmaceutical targets is a common method to identify potential lead molecules. For these HTS campaigns to be efficient and successful, continuous quality control of the compound collection is necessary and crucial. However, the large number of compound samples and the limited sample amount pose unique challenges. Presented here is a proof-of-concept study for a novel process flow for the quality control screening of small-molecule compound libraries that consumes only minimal amounts of samples and affords compound-specific molecular data. This process employs an acoustic sample deposition (ASD) technique for the offline sample preparation by depositing nanoliter volumes in an array format onto microscope glass slides followed by matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) analysis. An initial study of a 384-compound array employing the ASD-MALDI-MS workflow resulted in a 75% first-pass positive identification rate with an analysis time of <1 s per sample.