New Developments in Quantitative 3D Chemical Imaging

飞行时间二次离子质谱仪(ToF-SIMS)是一种优秀的化学分析方法，在学术界和工业界广泛应用于复杂样品的2D/3D表征。应用领域包括材料科学、生物学、医疗保健、能源等。在分析过程中，高能的“一次”离子射出撞击样品表面，导致“二次”分子离子被抛出，由质谱仪进行分析，以提供丰富的化学物质表征。扫描样品上的主光束提供2D表面成像(&gt；100 nm横向分辨率)，并通过在样品被侵蚀时顺序收集图像来提供3D亚表面成像(&gt；3 nm深度分辨率)。这种独特的分析能力组合意味着ToF-SIMS在单一分析中确定复杂样品中多种化学物质的组成和详细分布的潜力是无与伦比的。重要的是，这项技术支持“发现模式”研究，在这种模式下，分析不偏向预先选择的、标记的化合物，从而导致假设的产生。该分析是高度多元化和综合性的-一次测量可能检测到数百种物种，仅受过程的灵敏度限制，在这里我们试图将其提高100倍。这项建议解决了下一代样本的关键挑战，要求更高的灵敏度、更广泛的化学覆盖和可靠的量化，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。它建立在我们创新的ToF-SIMS仪器的国际领先声誉的基础上。初级离子的特性是决定样品表面撞击动力学和测量结果成功与否的基础。使用C60和Ar2000等多原子团簇弹从样品中生产完整的次级分子的挑战在很大程度上得到了解决，它们每次撞击产生约100个溅射分子。然而，这些分子中只有0.001-0.1%是以带电离子的形式产生的，这是它们检测所必需的。显然，电离效率还有巨大的提高空间。射弹引发的化学反应促进了溅射物种的电离，这一原理最近被我们和其他人的工作牢牢地确立了下来。我们现在必须在这些知识的基础上，开发互补的方法来迎接电离挑战，并提供定量的成分信息。我们已经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，该团队处于独特的地位，可以开展这一重要项目。基于&gt；在SIMS仪器创新方面20年的经验，通过EPSRC的支持和与英国工业的密切合作，我们将开发下一代反应离子束和分析方法。这将带来进一步的变革性性能提升，这对于满足未来的应用需求至关重要。我们的新结果将在新兴理论的框架内，以了解增强电离的机制，并支持弹丸参数的优化。他们将促进SIMS和相关技术基础物理过程理论模型的进一步发展。该项目是高度冒险的，提供了以新的基本理解为基础的超越最先进的分析能力。我们处于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的理想位置。数据质量的极大提高将导致对跨越许多科学和技术领域的广泛应用的新的理解。

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.