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（MS）已演变为在一系列环境，生物和健康学科中识别和量化分子的关键分析工具。 “样本中有什么？”的问题。和“多少？”仍然是生物学研究的关键组成部分。实际上，配备电喷雾电离（ESI）的液相色谱（LC）-MS被许多人视为黄金标准方法，并且在临床，环境和法医实验室中广泛使用。但是，LC-MS耗时，通常需要大量样品准备，并使用大量有机溶液。 矩阵辅助激光解吸电离（MALDI）-MS是一种替代分析策略，因为它快速（比LC-MS快100倍），简单，使用分数的溶液量，并且在样品中使用杂质（即样品制备时间更少）。 MALDI-MS是大分子（例如蛋白质）的理想选择，但是小分子（例如精神活性物质）的分析受到使用“基质”的阻碍。矩阵需要促进目标化合物的电离，这是MS分析的前提。然而，它在较低的质量范围内的分析中干扰了小分子。矩阵形成群集离子并产生明显的背景噪声。扩展MALDI-MS用于小分子的瓶颈是新物质的设计，可以在低质量范围内进行分析。 在此提案中，将设计新颖的Maldi物品。这些物品是表面修饰的纳米颗粒（纳米原木和金纳米颗粒），将传统物质或氨基酸移植到表面上。主要思想是利用金纳米颗粒和纳米座的光学特性，并将其与常规材料的电离能力相结合，用于分析小有机化合物。我们的初始投资表明了这种分析小药物的策略的希望。因此，将设计新物质，然后对加拿大人的心理活性物质进行测试，即大麻代谢物，阿片类药物（例如芬太尼）和苯丙胺。大麻的合法化和正在进行的阿片类药物危机都为发展快速和简单的分析策略造成了紧迫感。我们的驾驶假设是，具有常规基质和氨基酸部分的黄金和纳米木纳米颗粒功能化，将促进对生物样品（尿液和血浆）中精神活性物质的MALDI-MS分析。 从长远来看，研究计划的目的是使用纳米颗粒来开发简单的基于MALDI-MS的测定，以识别和量化精神活性物质。我开发自动化的简单测定的环境，并就精神活性物质的非法或有害使用提供快速的结果。该技术也可以应用于其他关注健康，安全和环境的小分子。