Advancing Liquid Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Toward Ultrahigh-Throughput Analysis
Advancing Liquid Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Toward Ultrahigh-Throughput Analysis
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DOI：
10.1021/acs.analchem.9b05202
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发表时间：
2020-02-18
影响因子：
7.4
通讯作者：
Cramer, Rainer
中科院分区：
文献类型：
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作者：
Krenkel, Henriette;Hartmane, Evita;Cramer, Rainer
使用质谱仪的无标记高通量筛选具有以每秒一个以上样本的速度提供快速大规模样本分析的潜力。这样的速度对于化合物文库、化验和未来在合理时间框架内对数百万样本的临床筛选非常重要。在这里，我们提出了一种液体大气压基质辅助激光解吸/电离(AP-MALDI)装置，用于高通量大规模样品分析(每秒5个样品)，用于三种物质类别(肽、抗生素和脂类)的分析。液体支持基质(LSM)用于标准物质和复杂生物液体(牛奶)的分析。吞吐量和分析的稳健性主要取决于样品组成的复杂性和目前商业硬件的局限性。然而，可以保守地估计，液体AP-MALDI在样品吞吐量方面的极限超过每秒10-20个样品。与包括电喷雾电离和固态MALDI在内的其他无标记MS方法以及使用标记多路复用的MS方法相比，这种水平的分析速度具有很强的竞争力，原则上也可以与液体AP-MALDI MS结合使用。
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.