Novel ion beams to enhance ionization in molecular secondary ion mass spectrometry

二次离子质谱仪(SIMS)是一种具有独特潜力的分析技术，可以在微米级上以2D和3D的形式探索复杂材料的化学结构，而不需要进行化学修饰或标记。表面化学被解吸(溅射)使用聚焦的高能(Kev)“初级”离子束，电离部分接受质谱分析。在过去的几年里，我们的研究重点是开发SIMS在生物细胞和组织研究中的应用，尽管其结果同样适用于其他复杂的系统，如有机电子材料。灵敏度是质谱学的中心问题，特别是在成像模式中，因为对空间分辨率水平的渴望意味着要分析的样品变得越来越小，并且永远不会有足够的离子产额。在EPSRC的支持下，我们已经非常成功地为SIMS引入并展示了新的初级离子束的力量，首先基于金团簇，然后基于C60，极大地提高了具有化学意义的大分子物种的离子产额。尽管有这些进展，低于1微米的空间分辨分析仍然是有问题的，因为在大多数情况下，有机SIMS(实际上在其他解吸质谱计，如MALDI和DESI)中的当前电离概率小于10-5。与这个问题相关的是矩阵效应的运算。化合物A的二次离子形成机制受发射区周围其他分子的化学作用的影响。A的离子产额可能被增强、降低甚至完全抑制，这取决于周围分子的同一性。这使得分析的不确定性和量化变得非常困难。在有机材料的情况下，有相当多的SIMS和MALDI文献证明了化合物A与其分子相邻分子相比的相对碱度对(A+H)+物种形成的影响。因此，基质效应的一个重要因素可能是由于离子发射区对质子的竞争。因此，在有机分析中，大多数分子相关离子是通过质子转移形成的，极大地增加发射区质子源分子的密度有望增加M+H或M-H产额。该项目将与小型离子束制造商Ionoptika有限公司合作，开发一种能够提供高密度H3O+或巨型水团簇离子(H2O)NH+(N=50至10000)的水离子束系统，该系统在撞击样品表面时将产生高密度的质子相关物种，将(A+H)+的二次离子产额提高至少10倍，并有望具有缓解基质效应的额外好处。该项目将是仪器开发和水束特性的结合，然后是对其操作的研究。水束系统将经过改进，并与之前为巨型Ar团束开发的离子光柱连接。研究了水束的最佳操作条件，并利用模型化合物系统研究了质子辅助离子产额提高程度和机理的基本原理。随后将对多组分模型材料进行研究，以考察水束对基质效应的影响以及成像质谱学中定量分析的改进。如果时间允许，我们希望对水束在MALDI MS中的有益作用进行原理证明研究。该项目的成功结果将极大地增强SIMS的能力和广泛吸收，使分子亚微米分析和成像成为可能，极大地改善基质效应的干扰，并显著改善定量测量。

Secondary ion mass spectrometry (SIMS) is an analytical technique with unique potential to probe the chemistry of complex materials in 2D and 3D on the micron level without the need for chemical modification or tagging. Surface chemistry is desorbed (sputtered) using a focused high energy (keV) 'primary' ion beam and the ionised fraction is subjected to mass spectrometric analysis. Our research over the last several years has focused on developing the application of SIMS to the study of biological cells and tissue, although the outcomes are equally applicable to other complex systems such as organic electronic materials. Sensitivity is the central issue in mass spectrometry particularly in the imaging mode because the desire for increasing levels of spatial resolution means that the sample to be analysed gets smaller and smaller and there can never be enough ion yield. With EPSRC's support we have very successfully introduced and demonstrated the power of new primary ion beams for SIMS, first based on gold clusters and then on C60, that have greatly increased the ion yield of the large molecular species that are chemically significant. Despite these advances spatially resolved analysis below 1 micron is problematical because the current ionisation probability in organic SIMS (and indeed in other desorption mass spectrometries such as MALDI and DESI) is less than 10-5 in most cases. Related to this problem is the operation of the matrix effect. The secondary ion formation mechanism for compound A is influenced by the chemistry of the other molecules surrounding it in the emission zone. The ion yield of A may be enhanced, reduced or even entirely suppressed dependent on the identity of the surrounding molecules. This makes analysis uncertain and quantification very difficult. In the case of organic materials there is a considerable SIMS and MALDI literature that demonstrates the influence of the relative basicity of compound A compared to its molecular neighbours on the formation of the (A+H)+ species. Thus a significant contributor to the matrix effect is probably due to competition for protons in the ion emission zone. Thus in the case of organic analysis where the majority of molecular related ions are formed by proton transfer, greatly increasing the density of proton source molecules in the emission zone is expected to increase the M+H or M-H yields. In a collaboration with a small ion beam manufacturer, Ionoptika Ltd, this project will develop a water ion beam system capable of delivering a high density of either H3O+ or giant water cluster ions (H2O)nH+ (N=50 to 10000), that on impact with the sample surface will generate a high density of proton related species to enhance the secondary ion yield of (A+H)+ by at least a factor of 10, and is expected to have the added benefit of relieving the matrix effect. The project will be a mix of instrument development and water beam characterisation followed by research into its operation. The water beam system will be built refined and interfaced with an ion optical column developed previously for a giant argon cluster beam. The optimum operational conditions for the water beam will be researched and then using model compound systems the fundamentals of the degree and mechanism of proton assisted ion yield enhancement will be researched. This will then be followed by studies of multi-component model materials to investigate the influence of the water beam on the matrix effect and the improvement of quantitative analysis in imaging mass spectrometry. Time permitting we hope to carry out proof of principle studies into the beneficial effects of the water beam in MALDI MS.The successful outcome of this project will very significantly enhance the capabilities and wide uptake of SIMS, enabling molecular sub-micron analysis and imaging, greatly ameliorating the interference of the matrix effect and significantly improving quantitative measurements.