Department of Chemistry , University of Reading , Whiteknights , Reading RG6 6AD , United Kingdom.
Waters Corporation , Stamford Avenue , Wilmslow SK9 4AX , United Kingdom.
Anal Chem. 2020 Feb 18;92(4):2931-2936. doi: 10.1021/acs.analchem.9b05202. Epub 2020 Jan 30.
Label-free high-throughput screening using mass spectrometry has the potential to provide rapid large-scale sample analysis at a speed of more than one sample per second. Such speed is important for compound library, assay and future clinical screening of millions of samples within a reasonable time frame. Herein, we present a liquid atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) setup for high-throughput large-scale sample analysis (>5 samples per second) for three substance classes (peptides, antibiotics, and lipids). Liquid support matrices (LSM) were used for the analysis of standard substances as well as complex biological fluids (milk). Throughput and analytical robustness were mainly dependent on the complexity of the sample composition and the current limitations of the commercial hardware. However, the ultimate limits of liquid AP-MALDI in sample throughput can be conservatively estimated to be beyond 10-20 samples per second. This level of analytical speed is highly competitive compared with other label-free MS methods, including electrospray ionization and solid state MALDI, as well as MS methods using multiplexing by labeling, which in principle can also be used in combination with liquid AP-MALDI MS.
基于质谱的无标记高通量筛选有可能以每秒超过一个样品的速度提供快速的大规模样品分析。对于化合物库、测定和未来临床筛选数以百万计的样品，这种速度在合理的时间范围内非常重要。本文介绍了一种用于高通量大规模样品分析（>每秒 5 个样品）的常压液相辅助激光解吸/电离（AP-MALDI）装置，可用于三类物质（肽、抗生素和脂质）的分析。液相支持基质（LSM）用于标准物质以及复杂生物流体（牛奶）的分析。通量和分析稳健性主要取决于样品组成的复杂性和商业硬件的当前限制。然而，液体 AP-MALDI 在样品通量方面的最终限制可以保守估计超过每秒 10-20 个样品。与其他无标记 MS 方法（包括电喷雾电离和固态 MALDI 以及基于标记的多重化的 MS 方法）相比，这种分析速度具有很强的竞争力，后几种方法原则上也可以与液体 AP-MALDI MS 结合使用。
