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

质谱法（MS）已经发展成为鉴定和定量分子在一系列环境，生物和健康学科的关键分析工具。“样本中有什么？”和“多少？”的问题仍然是生物学研究的关键组成部分。事实上，配备电喷雾电离（ESI）的液相色谱-质谱（LC -MS）被许多人认为是金标准方法，广泛应用于临床、环境和法医实验室。然而，LC-MS是耗时的，往往需要大量的样品制备，并使用大量的有机溶剂。基质辅助激光解吸电离(MALDI)-质谱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，并且耐受样品中的杂质（即更少的样品制备时间）。MALDI-MS是大分子（如蛋白质）的理想选择，但小分子（如精神活性物质）的分析则受到“基质”使用的阻碍。需要基质来促进目标化合物的电离，这是质谱分析的先决条件。然而，在较低质量范围的分析中，它会干扰小分子的出现。基质形成簇离子并产生显著的背景噪声。扩大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。基质是表面修饰的纳米颗粒（纳米金刚石和纳米金），在其表面接枝传统基质或氨基酸。主要的想法是利用金纳米粒子和纳米钻石的光学特性，并将其与传统基质的电离能力相结合，以分析小的有机化合物。我们的初步调查显示了这种分析小型药物的策略的前景。因此，将设计新的基质，然后对加拿大人关注的精神活性物质，即大麻代谢物、阿片类药物（如芬太尼）和安非他明进行测试。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和简单的分析战略。我们的驱动假设是，功能化金和纳米金刚石纳米颗粒与传统的基质和氨基酸部分将有助于MALDI-MS分析生物样品（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简单的基于MALDI-MS的检测方法，使用纳米颗粒来识别和量化精神活性物质。我设想开发一种简单的自动化分析方法，并提供关于非法或有害使用精神活性物质的快速结果。这项技术还可以应用于其他与健康、安全和环境有关的小分子。

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.