Chemical-imaging guided characterization of cellular populations

在化学系化学测量和成像项目的支持下，伊利诺伊大学香槟分校的Jonathan V. Sweedler教授和他的研究小组正在开发新的测量技术（基于质谱成像和化学分离），以高通量的方式探测单个细胞的化学成分。在一项测试应用中，新方法被用于分析和分类加利福尼亚海蛞蝓（一种重要的神经科学/生理动物模型）中枢神经系统内的所有细胞。这项研究有望为任何动物模型提供最完整的大脑细胞化学描述，提供将神经化学与大脑功能联系起来的基本细节。这项概念验证研究最终有望用于测量更复杂的大脑。跨学科的研究连接了分析化学和细胞神经生物学的世界。通过科学和非专业出版物、会议、高中和开放的外展计划以及跨学科的培训，广泛传播的结果确保了这项研究推进了NSF在科学教育和研究方面的使命。正在开发的分析平台集成了基于质谱的化学成像、毛细管电泳分离与质谱联用以及光学显微镜，能够在单细胞水平上对成千上万个细胞进行高通量表征，目的是对复杂组织（如大脑）的化学成分进行全局表征。第一个目标是创建新的细胞分离方法，然后基于激光解吸/电离和二次电离质谱成像的高通量，多重单细胞化学分析，以检查更大细胞群中的单个细胞。选择感兴趣的细胞的离线耦合的一种增强的方法，毛细管电泳质谱系统用于执行后续分析。在模型测试系统中，实验提供了有关海兔中枢神经系统细胞类型和化学异质性的详细信息。具有不同背景的本科生和研究生积极参与这些跨学科的努力，并参与公共和教育环境中的多个外展项目。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Jonathan V. Sweedler and his research group at the University of Illinois at Urbana-Champaign are developing new measurement technologies (based on mass spectrometry imaging and chemical separations) to probe the chemical composition of individual cells in a high throughput manner. In a test application, the new methods are used to analyze and classify all the cells within the central nervous system of the marine sea slug, Aplysia californica, an important neuroscience/physiological animal model. This research promises to provide the most complete description of cellular chemistry of the brain for any animal model, providing fundamental details linking neurochemistry to brain function. This proof-of-concept study is ultimately expected to lead to measurement of more complex brains. The interdisciplinary research bridges the worlds of analytical chemistry and cellular neurobiology. The broad-based dissemination of the results through scientific and lay publications, conferences, high school and open house outreach programs, and training across multiple disciplines assures that this research advances NSF's mission in science education and research.The analytical platform being developed integrates mass spectrometry-based chemical imaging, capillary electrophoresis separations hyphenated to mass spectrometry, and optical microscopy to enable high-throughput characterization of tens of thousands of cells at the single-cell level, with an aim of global characterization of the chemical constituents of complex tissues such as the brain. The first goal is to create novel cell isolation approaches and then high-throughput, multiplex single-cell chemical analyses based on laser desorption/ionization and secondary ionization mass spectrometry imaging to examine individual cells within larger cell populations. An enhanced method of off-line coupling of selected cells of interest to a capillary electrophoresis mass spectrometry system is used to perform follow-up assays. In a model test system, the experiments provide detailed information on the cell types and chemical heterogeneity within the Aplysia central nervous system. Undergraduate and graduate students with diverse backgrounds are actively involved in these interdisciplinary efforts, and are involved in multiple outreach programs in both public and educational settings.