Development of cell-based drug discovery assays using high-throughput MALDI TOF mass spectrometry

质谱（MS）是一种新兴的技术，用于识别和表征调节生物靶标的药物，提供了一种无标签的直接检测方法。与目前的经典方法相比，该技术能够应用更多与生理相关的分析，减少时间和成本，提高药物发现过程的效率。过去，基于质谱的分析技术的通量是有限的，但MALDI-TOF-MS设备和斑点技术领域的最新发展大大提高了这种方法的小型化和速度。然而，MALDI的应用是基于一个基质相容的样品制备步骤，并且局限于一定的分析物空间。这需要确定maldi兼容的生理相关分析条件，以及开发快速和可重复的液体处理程序。博士的工作将侧重于评估将MALDI-TOF-MS的应用扩展到基于细胞的高通量筛选分析，并研究化学修饰以增加

"Mass spectrometry (MS) is an emerging technology for identifying and characterizing drugs that modulate biological targets, offering a label-free, direct detection method. This technology enables the application of more physiologically relevant assays and reduces time and costs compared to current classical approaches increasing the efficiency of the drug discovery process. In the past, the throughput of MS-based assay technologies was limited, but recent developments in the field of MALDI-TOF-MS devices and spotting technologies substantially increased the ability for miniaturization and speed of such approaches. However, the application of MALDI is based on a matrix-compatible sample preparation step and is limited to a certain space of analytes. This requires the identification of MALDI-compatible, physiological relevant assay conditions, as well as development of fast and reproducible liquid handling procedures. The PhD work will focus on the evaluation to extend the application of MALDI-TOF-MS to cell-based assays in high-throughput screening and investigate chemical modifications to increase "