ORGANIC SECONDARY ION IMAGING

本研究的目的是开发一种方法来确定 目标有机化合物在生物组织中的空间分布。 药物、化合物及其代谢物的痕量分析是一种 应用的方法，但分析的分布更多 浓缩的物质如磷脂也是可能的。到 为了实现这一点，将二次电离（SI）微探针连接到 三重四极杆串联质谱仪（MS/MS），以制备西姆斯/MS 微探针这种仪器可以从一个原子中产生离子。 在样品上的特定位置，使用微透镜的精细聚焦光束， 初级离子，并与串联质谱，测量强度 具有特定化学结构的二次离子。三种方法将 用于提高方法的灵敏度。 第一，使用多原子 20 keV能量的初级离子，用于使用静态成像（低初级剂量） 将开发西姆斯和MS/MS。第二，协调使用两个主要 具有不同溅射和电离特性的离子束将 用于消除初级离子束损伤的影响，允许平均 和深度剖析。第三，化学处理样品将 研究用于增强特征发射和减轻初级 离子损伤灵敏度的提高将使空间分辨率 改善至优于10微摩尔。标准样品制备和 将开发预处理方法，以便最大限度地减少伪影 并且可以测量和预测灵敏度。

The objective of this research is development of a method to determine the spatial distribution of targeted organic compounds in biological tissue. Trace analysis for drugs, compounds and their metabolites is one application of the method, but analysis of the distribution of more concentrated species such as phospholipids will also be possible. To accomplish this, a secondary ionization (SI) microprobe is attached to a triple quadrupole tandem mass spectrometer (MS/MS) to make a SIMS/MS microprobe. This instrument makes it possible to generate ions from a particular location on the sample using a finely focused beam of the primary ions, and with tandem mass spectrometry, measure the intensity of secondary ions with a particular chemical structure. Three approaches will be used to enhance sensitivity of the methods. First, use of polyatomic primary ions of 20 keV energy for imaging using static (low primary dose) SIMS and MS/MS will be developed. Secondly, coordinated use of two primary ion beams, with different sputtering and ionization characteristics will be used to remove the effects of primary ion beam damage, permit averaging and depth profiling. Third, chemical treatment of samples will be investigated for enhancing characteristic emission and mitigating primary ion damage. Improved sensitivity will allow for spatial resolution to be improved to better than 10 micromoles. Standard sample preparation and pretreatment methods will be developed so that artifacts can be minimized and sensitivity can be measured and predicted.