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

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.