Clinical Protein Science & Imaging, Dept. of Measurement Technology and Industrial Electrical Engineering, Lund University, BMC C13, SE-221 84 Lund, Sweden.
J Proteomics. 2010 Apr 18;73(6):1270-8. doi: 10.1016/j.jprot.2010.02.021. Epub 2010 Mar 1.
The ultimate goal of MALDI-Imaging Mass Spectrometry (MALDI-IMS) is to achieve spatial localization of analytes in tissue sections down to individual tissue compartments or even at the level of a few cells. With compound tissue imaging, it is possible to track the transportation of an unlabelled, inhaled reference compound within lung tissue, through the application of MALDI-IMS. The procedure for isolation and preparation of lung tissues is found to be crucial in order to preserve the anatomy and structure of the pulmonary compartments. To avoid delocalization of analytes within lung tissue compartments we have applied an in-house designed nano-spotter, based on a microdispenser mounted on an XY table, of which movement and spotting functionality were fully computer controlled. We demonstrate the usefulness of this platform in lung tissue sections isolated from rodent in vivo model, applied to compound tissue imaging as exemplified with the determination of the spatial distribution of (1alpha,2beta,4beta,7beta)-7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0(2,4)]nonane, also known as tiotropium. We provide details on tissue preparation protocols and sample spotting technology for successful identification of drug in mouse lung tissue by using MALDI-Orbitrap instrumentation.
基质辅助激光解吸电离成像质谱（MALDI-IMS）的最终目标是实现组织切片中分析物的空间定位，达到单个组织隔室甚至几个细胞的水平。通过 MALDI-IMS，可以追踪未标记的吸入参考化合物在肺组织中的运输。为了保留肺隔室的解剖结构和形态，发现分离和制备肺组织的程序是至关重要的。为了避免分析物在肺组织隔室中的定位不准，我们应用了一种内部设计的纳米点样器，它基于安装在 XY 台上的微分配器，其运动和点样功能完全由计算机控制。我们展示了这个平台在从体内模型的啮齿动物中分离的肺组织切片中的实用性，应用于复合组织成像，例如确定（1alpha,2beta,4beta,7beta）-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0(2,4)]nonane 的空间分布，该化合物也称为噻托溴铵。我们提供了组织准备方案和样品点样技术的详细信息，用于使用 MALDI-Orbitrap 仪器成功识别小鼠肺组织中的药物。
