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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762124
• 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（MS）已经发展成为一种关键的分析工具，用于识别和量化环境，生物和健康学科中的分子。“样品中有什么”的问题？“和“多少钱？“仍然是生物学研究的重要组成部分。事实上，配备电喷雾离子化（ESI）的液相色谱（LC）-MS被许多人认为是金标准方法，广泛用于临床，环境和法医实验室。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是一种替代分析策略，因为它快速（比LC-MS快100倍），简单，使用少量溶剂，并耐受样品中的杂质（即更少的样品制备时间）。MALDI-MS是大分子的理想选择，例如蛋白质，但小分子的分析，例如精神活性物质，受到“基质”使用的阻碍。需要基质来促进目标化合物的电离，这是MS分析的先决条件。然而，它会干扰较低质量范围的分析，在那里会出现小分子。基质形成团簇离子并产生显著的背景噪声。扩展MALDI-MS用于小分子的瓶颈是设计新的基质，允许在低质量范围内进行分析。 在这个建议中，新的MALDI矩阵将被设计。基质是表面改性的纳米颗粒（纳米金刚石和金纳米颗粒），常规基质或氨基酸被接枝在其表面上。其主要思想是利用金纳米颗粒和纳米金刚石的光学性质，并将其与常规基质的电离能力联合收割机结合起来，用于分析小的有机化合物。我们的初步调查显示，这种策略有希望分析小型药物。因此，将设计新的矩阵，然后对加拿大人关注的精神活性物质，即大麻代谢物、类阿片（如芬太尼）和苯丙胺进行测试。大麻合法化和持续的阿片类药物危机都迫切需要制定快速简单的分析战略。我们的驱动假设是，用常规基质和氨基酸部分官能化金和纳米金刚石纳米颗粒将促进生物样品（尿液和血浆）中精神活性物质的MALDI-MS分析。 从长远来看，该研究计划的目标是开发简单的MALDI-MS检测方法，使用纳米颗粒来识别和量化精神活性物质。我设想开发自动化的简单检测方法，并提供有关非法或有害使用精神活性物质的快速结果。该技术还可以应用于其他与健康、安全和环境有关的小分子。