Optimizing Mass Spectrometry Imaging for Next Generation Pharmaceutical Research

成像质谱（IMS）是一种无标记的分子成像技术，在临床研究中具有新兴的应用。具有细胞空间分辨率的IMS方法主要有二次离子质谱（西姆斯）和基质辅助激光解吸电离（MALDI）两种，它们分别使用离子束和激光来捕获生物材料的分子快照。这些互补技术具有独特的优势和不同的挑战。例如，由于离子束的性质和先进的离子束聚焦技术，亚微米横向分辨的离子图像在西姆斯成像中是常见的，然而，射弹的强烈轰击限制了分子离子产率。MALDI和西姆斯成像共同填补了无标记生物分子成像的分析性能空白，并生成组织中蛋白质、脂质和代谢物的全面图像。该研究计划将侧重于提高离子图像质量（即分子灵敏度，定量能力和横向分辨率测量），并建立联合收割机西姆斯和MALDI IMS相结合的协同工作流程。研究计划中建立的协议和方法将为表征和改善离子图像质量提供基础。研究计划的集体成果将通过改善组织和细胞中生物分子和药物化合物的检测，确保IMS技术在临床组织病理学和临床药理学中的接受程度。

Imaging mass spectrometry (IMS) is a label-free molecular imaging technique with emerging applications in clinical research. There are two IMS methods with cellular spatial resolution, secondary ion mass spectrometry (SIMS) and matrix assistant laser desorption ionization (MALDI) using ion beams and laser, respectively, to capture molecular snapshots of biological materials. These complementary techniques have unique advantages and different challenges. For example, sub-micron laterally resolved ion images are common in SIMS imaging owing to the nature of the ion beam and advance ion beam focusing techniques, however, the harsh bombardment of the projectile limits molecular ion yields. Together MALDI and SIMS imaging fill the analytical performance gaps for label-free biomolecular imaging and produce a comprehensive picture of the proteins, lipids, and metabolites in tissue. The research program will focus on improving the ion image quality (i.e. molecular sensitivity, quantification ability, and lateral resolution measurements) and establishing synergistic workflows that combine SIMS and MALDI IMS. The protocols and methodologies established in the research program will provide a basis for characterizing and improving ion image quality. The collective outcome of the research program will ensure progress towards the acceptance of IMS technology in clinical histopathology and clinical pharmacology by improving the detection of biomolecule and pharmaceutical compounds in tissue and cells.