New surface-modified nanoparticles as matrices to enhance mass spectrometric analysis of substance of abuse by matrix assisted laser desorption ionization

新型表面改性纳米粒子作为基质，通过基质辅助激光解吸电离增强滥用物质的质谱分析

• 批准号: RGPIN-2020-04332
• 负责人: ElAneed, Anas
• 金额: $ 2.62万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716977
• 关键词: New; surface; modified; nanoparticles; matrices

Mass spectrometry (MS) has evolved to become a key analytical tool for identifying and quantifying molecules in a range of environmental, biological, and health disciplines. The questions of “what is in the sample?” and “how much?” remain critical components of biological studies. In fact, liquid chromatography (LC)-MS, equipped with electrospray ionization (ESI), is considered by many as the gold standard approach and it is used widely in clinical, environmental and forensic laboratories. However, LC-MS is time consuming, often requires substantial sample preparation, and uses a large amount of organic solvents. Matrix assisted laser desorption ionization (MALDI)-MS is an alternative analytical strategy as it is fast (100 times faster than LC-MS), simple, uses fraction amounts of solvents, and tolerates impurities in a sample (i.e. less sample preparation time). MALDI-MS is ideal for large molecules, such as proteins, but the analysis of small molecules, such as psychoactive substances, is hampered by the use of a “matrix”. The matrix is required to facilitate the ionization of target compounds, a precondition for MS analysis. It interferes, however, in the analysis at the lower mass range, where small molecules will appear. The matrix forms cluster ions and creates significant background noise. The bottleneck in expanding the use of MALDI-MS for small molecules is the design of new matrices that allows for the analysis at the low mass range. In this proposal, novel MALDI matrices will be designed. The matrices are surface modified nanoparticles (nanodiamonds and gold nanoparticles), to which either conventional matrices or amino acids are grafted on the surface. The main idea is to take advantage of the optical properties of the gold nanoparticles and nanodiamonds and to combine this with the ionization ability of conventional matrices for the analysis of small organic compounds. Our initial investigation showed the promise of such a strategy to analyze small pharmaceuticals. Therefore, new matrices will be designed then tested on psychoactive substances of concern to Canadians, namely cannabis metabolites, opioids (e.g. fentanyl), and amphetamines. Both the legalization of cannabis and the ongoing opioid crisis have created urgency for the development of fast and simple analytical strategies. Our driving hypothesis is that functionalizing gold and nanodiamond nanoparticles with conventional matrices and amino acid moieties will facilitate MALDI-MS analysis of psychoactive substances within biological samples (urine and plasma). In the long term, the aim of the research program is to develop simple MALDI-MS based assays using nanoparticles to identify and quantify psychoactive substances. I envision developing simple assays that are automated and provide fast results regarding the illegal or harmful use of psychoactive substances. The technology can also be applied to other small molecules of concern to health, safety and the environment.

质谱仪(MS)已经发展成为一种关键的分析工具，用于在一系列环境、生物和健康学科中识别和量化分子。“样本中有什么？”以及“多少钱？”仍然是生物学研究的关键组成部分。事实上，配备了电喷雾电离(ESI)的LC-MS被许多人认为是金标准方法，它在临床、环境和法医实验室中得到了广泛的应用。然而，LC-MS是耗时的，通常需要大量的样品制备，并且使用大量的有机溶剂。 基质辅助激光解吸电离(MALDI)-MS是一种替代的分析方法，因为它速度快(比LC-MS快100倍)，简单，只使用少量的溶剂，并且允许样品中的杂质(即更少的样品准备时间)。MALDI-MS是蛋白质等大分子的理想选择，但对精神活性物质等小分子的分析因使用“基质”而受阻。需要基质来促进目标化合物的电离，这是进行MS分析的先决条件。然而，它会干扰在较低质量范围内的分析，因为在较低质量范围内会出现小分子。该基质形成团簇离子并产生显著的背景噪声。扩大MALDI-MS用于小分子分析的瓶颈是设计新的矩阵，允许在低质量范围内进行分析。 在该方案中，将设计新颖的MALDI矩阵。基质是表面修饰的纳米颗粒(纳米钻石和金纳米颗粒)，传统的基质或氨基酸被嫁接到表面。其主要思想是利用金纳米颗粒和纳米钻石的光学性质，并将其与传统基质的电离能力相结合，用于分析小分子有机化合物。我们的初步调查显示，这种策略在分析小型药物方面是有希望的。因此，将设计新的矩阵，然后对加拿大人关心的精神活性物质进行测试，即大麻代谢物、阿片类药物(如芬太尼)和苯丙胺。大麻合法化和目前的阿片类药物危机都迫切需要制定快速而简单的分析战略。我们的驱动假设是，将金和纳米钻石纳米颗粒与传统基质和氨基酸部分功能化，将有助于MALDI-MS分析生物样本(尿液和血浆)中的精神活性物质。 从长远来看，该研究计划的目标是开发基于MALDI-MS的简单分析方法，使用纳米颗粒来识别和量化精神活性物质。我设想开发一种简单的分析方法，这种方法是自动化的，可以对非法或有害使用精神活性物质的情况提供快速结果。这项技术也可以应用于其他与健康、安全和环境有关的小分子。