3D Momentum Imaging of Matrix-Assisted Laser Desorption/Ionization (MALDI) in the Time Domain

在化学系化学测量与成像计划的支持下，韦恩州立大学的文力教授和他的团队正在进行与质谱学相关的基础研究，质谱学是一种强大的化学分析方法，在生物、化学和医学中有着广泛的应用。具体地说，Li小组正在研究基质辅助激光解吸/电离(MALDI)的机制，这是一种广泛使用的产生离子的技术，并进行了质量分析。尽管经过了几十年的研究努力，但对MALDI潜在机制的细节的了解仍然不完善。该项目旨在利用新开发的研究工具加强我们对这些细节的了解，以提供对MALDI过程的前所未有的见解。预计洞察力的提高可能会导致敏感度的提高。从事这些研究的学生将获得出色的跨学科培训。李博士还积极接触高中生，努力提高他们对科学职业道路的兴趣。该项目旨在加强对MALDI中初级电离机制的了解，并旨在提高该技术在检测与生物相关的复杂和大分子方面的灵敏度。飞秒和皮秒激光与高分辨率的电子和离子的三维动量成像相结合，目的是提供关于电离动力学的前所未有的细节。将设计使用超短脉冲泵浦将样品损失减少到中性解吸的方案，目的是显著提高灵敏度。具体来说，将整合三个项目来揭示复杂的动力学：1)开发一种基于电子成像的新的超快测温方法，分辨率为数十皮秒，用于测量样品的时间分辨温度；2)在DHB上进行时间分辨测温测量，以评估各种模型的有效性；以及3)研究一种新的飞秒脉冲驱动的激光解吸/电离机制。这些研究预计将阐明初始电离过程的细节，并可能导致MALDI敏感性的增强。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Wen Li and his group at Wayne State University are undertaking fundamental studies related to mass spectrometry, a powerful method of chemical analysis with broad applications in biology, chemistry, and medicine. Specifically, the Li group is studying the mechanism of Matrix-Assisted Laser Desorption/Ionization (MALDI), a widely employed technique for producing ions that are subjected to mass analysis. Despite decades of research effort, knowledge of the details of the underlying mechanism of MALDI remains imperfect. This project aims to enhance our understanding of these details using newly developed research tools to provide unprecedented insights into the MALDI process. It is expected that improved insight may lead to improved sensitivity. Students engaged in these studies will gain excellent interdisciplinary training. Dr. Li is also active in outreach to high school students, in efforts to enhance their interest in career paths in science.The project aims to enhance understanding of the mechanisms of primary ionization in MALDI and aims to improve the sensitivity of the technique in detecting complex and large molecules of biological relevance. Femto- and picosecond lasers coupled with high-resolution three-dimensional momentum imaging of both ejected electrons and ions will be employed with the goal of providing unprecedented details about ionization dynamics. Schemes using ultrashort pulse pumping to reduce the sample loss to neutral desorption will be devised with an aim of significantly increasing sensitivity. Specifically, three projects will be integrated to unravel the complex dynamics: 1) developing a novel ultrafast thermometry method based on electron imaging with a resolution of tens of picoseconds for measuring the time-resolved temperatures of samples; 2) carrying out time-resolved thermometry measurements on DHB to assess the validity of various models; and 3) investigating a new laser desorption/ionization mechanism driven by femtosecond pulses. These studies are expected to illuminate details of the initial ionization process and may lead to enhancement of MALDI sensitivity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.