ORGANIC SECONDARY ION IMAGING

有机二次离子成像

• 批准号: 2180947
• 负责人: PETER Justin TODD
• 金额: $ 17.84万
• 依托单位: LOCKHEED MARTIN ENERGY SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2180947
• 关键词: biomedical equipment development; drug detection; mass spectrometry; organic chemicals; tissue /cell preparation

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.

这项研究的目的是开发一种方法来确定 生物组织中靶向有机化合物的空间分布。 药物、化合物及其代谢物的痕量分析是一种 应用的方法不多，但分析的分布较多 磷脂等浓缩物种也将成为可能。至 要做到这一点，二次电离(SI)微探针被连接到一个 用于制造SIMS/MS的三重四极串联质谱计 微探头。这台仪器使我们有可能从一种 在样品上使用细微聚焦的波束 初级离子，并用串联质谱仪测量其强度 具有特殊化学结构的二次离子。三种方法将 用来提高方法的灵敏度。第一，多原子的使用 用于静态成像的20keV能量的初级离子(低初级剂量) 将开发SIMS和MS/MS。第二，协调使用两种主要 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 和深度剖面图。第三，将对样品进行化学处理 关于提高特征排放和减少一次排放的研究 离子损伤。提高敏感度将使空间分辨率 改进到好于10微摩尔。标准样品制备和分析 将开发预处理方法，以便将人工制品降至最低 灵敏度是可以测量和预测的。