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New Developments in Quantitative 3D Chemical Imaging

定量 3D 化学成像的新进展

基本信息

批准号：
EP/S019863/1
负责人：
Nicholas Lockyer
金额：
$ 107.65万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FS019863%2F1
关键词：
New Developments Quantitative 3D Chemical

项目摘要

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is an outstanding method of chemical analysis, used extensively in academia and industry to characterise complex samples in 2D/3D. Application areas include materials science, biology, healthcare, energy etc. In the analysis the high-energy 'primary' ion projectile impact on a sample surface, causes ejection of 'secondary' molecular ions which are analysed by a mass spectrometer to provide chemically-rich material characterisation. Scanning the primary beam across the sample provides 2D surface imaging (>100 nm lateral resolution) and by sequentially collecting images while the sample is eroded, 3D sub-surface imaging (>3 nm depth resolution). This unique combination of analytical capabilities means ToF-SIMS is unmatched in its potential to determine, in a single analysis, the composition and detailed distribution of multiple, chemicals in complex samples. Importantly, this technology supports 'discovery mode' research, where the analysis is not biased towards pre-selected, labelled compounds, and therefore leads to hypothesis generation. The analysis is highly-multiplexed and comprehensive - hundreds of species can be potentially detected in a single measurement, limited only by the sensitivity of the process, which here we seek to enhance 100-fold.This proposal addresses critical challenges from next-generation samples demanding greater sensitivity, broader chemical coverage and reliable quantification to address issues including sub-cellular drug localisation and nanoscale molecular materials. It builds on our internationally-leading reputation for innovative ToF-SIMS instrumentation. The characteristics of the primary ion are fundamental in determining impact dynamics at the sample surface and the success of the resulting measurement. The challenge of producing intact secondary molecules from the sample has been largely solved using polyatomic cluster projectiles e.g. C60 and Ar2000 which produce ~100 sputtered molecules per impact. However, only ~0.001-0.1% of these molecules are produced as charged ions, which is necessary for their detection. Clearly there is huge room for improvement in the ionisation efficiency. The principle of projectile-initiated chemical reactions promoting ionisation of sputtered species has recently been firmly established by our work and that of others. We must now build on this knowledge and develop complementary approaches to meet the ionisation challenge and deliver quantitative compositional information.We have assembled a multidisciplinary team of international experts from academia and industry, which is uniquely positioned to pursue this important project. Building on >20 years' experience in innovation of SIMS instrumentation, enabled through EPSRC support and close collaboration with UK Industry, we will develop next-generation reactive ion beams and analytical methodology. This will deliver further transformative gains in performance which are critical to meet future application needs. Our novel results will be framed within the context of emerging theory to understand mechanisms of enhanced ionisation and to underpin the optimisation of projectile parameters. They will stimulate further development of theoretical models of the physical processes underlying SIMS and related techniques.The project is highly-adventurous, providing beyond state-of-the-art analytical capability underpinned with new fundamental understanding. We are ideally placed to exploit this through the interdisciplinary research collaborations at the Manchester Institute of Biotechnology and the Sir Henry Royce Institute for Advanced Materials. The vastly increased quality of data will result in new understanding in a wide range of applications spanning many areas of science and technology.

飞行时间二次离子质谱（ToF-SIMS）是一种杰出的化学分析方法，广泛应用于学术界和工业界，以二维/三维的方式对复杂样品进行分析。应用领域包括材料科学、生物学、医疗保健、能源等。在分析中，高能“初级”离子射弹撞击样品表面，导致“次级”分子离子喷射，这些分子离子由质谱仪分析，以提供化学丰富的材料表征。在样品上扫描初级光束提供2D表面成像（>100 nm横向分辨率），并且通过在样品被侵蚀时顺序地收集图像，提供3D亚表面成像（>3 nm深度分辨率）。这种独特的分析能力组合意味着ToF-SIMS在单次分析中确定复杂样品中多种化学物质的组成和详细分布方面具有无与伦比的潜力。重要的是，这项技术支持“发现模式”研究，其中分析不偏向于预先选择的标记化合物，因此导致假设生成。该分析是高度多路复用和全面的-数百种物质可以在一次测量中潜在地被检测到，仅受过程灵敏度的限制，在这里我们寻求提高100倍。该提案解决了下一代样品的关键挑战，这些样品要求更高的灵敏度，更广泛的化学覆盖范围和可靠的定量，以解决包括亚细胞药物定位和纳米级分子材料在内的问题。它建立在我们在创新ToF-SIMS仪器方面的国际领先声誉之上。一次离子的特性是确定样品表面的冲击动力学和测量成功的基础。从样品中产生完整的二次分子的挑战已经在很大程度上解决了使用多原子团簇射弹，例如C60和Ar 2000，每次撞击产生约100个溅射分子。然而，这些分子中只有约0.001-0.1%是以带电离子的形式产生的，这是检测它们所必需的。显然，在电离效率方面存在巨大的改进空间。射弹引发的化学反应促进溅射物种的电离的原则，最近已经牢固地建立了我们的工作和他人。现在，我们必须在此基础上开发互补方法，以应对电离挑战并提供定量成分信息。我们组建了一支由来自学术界和工业界的国际专家组成的多学科团队，这是开展这一重要项目的独特优势。基于超过20年的西姆斯仪器创新经验，通过EPSRC的支持和与英国工业界的密切合作，我们将开发下一代反应离子束和分析方法。这将带来进一步的性能变革，这对于满足未来的应用需求至关重要。我们的新结果将框架内的新兴理论的背景下，了解增强电离的机制，并支持抛射体参数的优化。他们将促进西姆斯和相关技术基础物理过程的理论模型的进一步发展。该项目是高度冒险的，提供超越最先进的分析能力，以新的基本理解为基础。我们非常适合通过曼彻斯特生物技术研究所和亨利罗伊斯爵士先进材料研究所的跨学科研究合作来利用这一点。数据质量的大幅提高将导致对跨越许多科学和技术领域的广泛应用的新理解。