3D OrbiSIMS: Label free chemical imaging of materials, cells and tissues

这一应用是为了飞行时间二次离子质谱仪(ToF-SIMS)，它具有独特的最先进的3D成像能力，通过集成高规格的OrbitRapTM质谱仪实现了前所未有的质量分辨率。此外，该仪器具有极高的空间分辨率，并辅之以低温制备设施，使其能够保存生物细胞和组织等水合样品的天然结构。该仪器利用一次离子撞击产生的最外层1-2 nm处的二次离子碎片的表面质谱学，提供了材料的无标记分子表征。当这种表面灵敏度与溅射光束相结合时，它可以产生高横向(&lt；100 nm)和垂直(~3 nm)分辨率的材料的3D化学分析。新兴的下一代现实世界系统和设备在生物医学植入物、药物输送系统、有机电子设备和工程设备等各种研究领域展示出越来越复杂的样品类型。这些设备的设计和创新是以材料特性为基础的，然而它们的化学复杂性可能会阻碍它们的特性。该仪器将提供对给定样品的真实化学3D内部环境的毫不妥协的准确描述，专门用于有机材料的分析。真实世界系统的详细化学特征将在多学科范围的新研究中应用，同时支持药学院、生命科学学院和工程学院在药物输送、抗菌素耐药性和电子学等领域工作的PI和Co-IS领导的现有研究计划。ToF-SIMS实验中丰富的化学信息被发现为一系列现实世界材料系统的性能提供了关键信息。该仪器工作在超高真空下，可用于表征任何特定化学物质的固体样品。重要的是，这是一种无标记的方法，提供了化学的完整特征，不受样品制备选择和光学显微镜细胞和组织成像中使用的荧光团引入的人工制品的影响。使用冷冻制备设备，该仪器将在分析冷冻水合液体或半固体(例如干细胞和细菌)的能力方面处于世界领先地位，从而确保它可以用于分析非常广泛的材料，因此其能力真正是跨学科的。诺丁汉大学是唯一拥有这种仪器的地点，该仪器自80年代末以来在药物和材料科学中的TOF-SIMS应用方面具有国际声誉，以及可应用于最大限度地利用这种组合的活跃的低温样品电子显微镜计划。诺丁汉大学拥有一个中央设施，仪器将放置在那里，设备可以进入，重要的是为内部和外部的学术研究提供专业知识。该仪器将促进内部学术研究计划，包括EPSRC的高级治疗和纳米医学、碳捕获和储存与清洁化石能源、可持续化学、添加剂制造以及3D打印和再生医学方面的博士培训中心。此外，MI大学和其他国家研究机构将利用现有的合作联系，在以下领域实现3D材料表征的阶段性变化：制药学(斯特拉斯克莱德大学Alistair Florence教授)、再生医学(伦敦帝国学院Molly Stevens教授)、半导体材料、器件和技术(Durham大学David Wood教授)。

This application is for a time of flight secondary ion mass spectrometer (ToF-SIMS) with unique state-of-the-art 3D imaging capability exhibiting unprecedented mass resolution achieved through the integration of a high specification OrbitrapTM mass spectrometer. Additionally, the instrument is capable of extremely high spatial resolution and is complemented by cryo-preparation facilities which allow the preservation of the native structure of hydrated samples such as biological cells and tissue. The instrument provides a label free molecular characterisation of materials using surface mass spectrometry of liberated secondary ion fragments generated by primary ion impaction from the outermost 1 - 2 nm. When this surface sensitivity is combined with a sputtering beam it produces a 3D chemical analysis of materials at high lateral (< 100 nm) and vertical (~ 3 nm) resolution.The emerging next generation of real world systems and devices exhibit an increasing complexity in sample type throughout a variety of research areas, such as biomedical implants, drug delivery systems, organic electronics devices and engineering devices. The design and innovation of these devices is underpinned by materials characterisation, however their chemical complexity can be prohibitive to their characterisation. The instrument will offer an uncompromisingly accurate portrayal of the true chemical 3D internal environment of a given sample, specialising in the analysis of organic materials.The detailed chemical characterisation of real world systems will have applications in a multi-disciplinary range of new research whilst supporting existing research programmes led by the PI and Co-Is within the Schools of Pharmacy, Life Sciences and Faculty of Engineering working in the areas of drug delivery, antimicrobial resistance and electronics amongst others. The chemically rich information in the ToF-SIMS experiment has been found to provide critical information in the performance of a range of real world material systems. The instrument operates under ultra-high vacuum and can be used to characterise solid samples of any given chemistry. Critically this is a label free approach, providing a full characterisation of the chemistry, unbiased by sample preparation choices and artefacts introduced by fluorophores employed in cell and tissue imaging by optical microscopy. Using the cryo -preparation facilities, the instrument will be world leading in its capability to analyse frozen hydrated liquids or semi-solids (for example, stem cells and bacteria) thereby ensuring that it can be used to analyse a very wide range of materials and is therefore truly transdisciplinary in its capacity.The University of Nottingham is uniquely situated to house such an instrument with an international reputation in the application of ToF-SIMS in the pharmaceutical and materials sciences since the late 80s and active cryo-sample electron microscopy programmes which can be applied to maximise the utility of this combination. The University of Nottingham hosts a centralised facility where the instrument will be located with equipment access and importantly expertise provided for internal and external academic research. Internal academic research programmes that will be facilitated by this instrument including EPSRC Centres for Doctoral Training in Advanced Therapeutics & Nanomedicines, Carbon Capture and Storage and Cleaner Fossil Energy, Sustainable Chemistry, Additive Manufacturing and 3D Printing and Regenerative Medicine. Additionally, existing collaborative links will be exploited within the MI universities and amongst other national institutes to enable a step change in the 3D materials characterisation in areas such as pharmaceutics (Prof. Alistair Florence, University of Strathclyde), regenerative medicine (Prof. Molly Stevens, Imperial College London), semiconductor materials, devices and technology (Prof. David Wood, University of Durham).