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

该应用程序是用于飞行时间二次离子质谱仪（ToF-SIMS），具有独特的最先进的3D成像能力，通过集成高规格OrbitrapTM质谱仪，展示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，并配有冷冻制备设备，可以保存水合样品（如生物细胞和组织）的天然结构。该仪器使用表面质谱法对由最外层1 - 2nm的初级离子撞击产生的释放次级离子碎片进行无标签分子表征。当这种表面灵敏度与溅射光束相结合时，它可以在高横向（< 100 nm）和垂直（~ 3 nm）分辨率下产生材料的3D化学分析。新兴的下一代现实世界系统和设备在各种研究领域中，如生物医学植入物、药物输送系统、有机电子设备和工程设备，在样品类型方面表现出越来越大的复杂性。这些设备的设计和创新以材料表征为基础，然而它们的化学复杂性可能会阻碍它们的表征。该仪器将对给定样品的真实化学3D内部环境提供毫不妥协的准确描绘，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应用于多学科的新研究，同时支持由药学院、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等领域工作的PI和Co-Is领导的现有研究项目。在ToF-SIMS实验中发现的化学丰富信息为一系列真实世界材料系统的性能提供了关键信息。该仪器在超高真空下工作，可用于表征任何给定化学物质的固体样品。关键的是，这是一种无标签的方法，提供了化学的完整特征，不受样品制备选择的影响，也不受光学显微镜在细胞和组织成像中使用的荧光团引入的人工制品的影响。使用低温制备设备，该仪器在分析冷冻水合液体或半固体（例如，干细胞和细菌）方面的能力将处于世界领先地位，从而确保它可以用于分析非常广泛的材料，因此在其能力上是真正的跨学科。自80年代末以来，诺丁汉大学在制药和材料科学领域的ToF-SIMS应用方面享有国际声誉，并且可以应用活性冷冻样品电子显微镜计划来最大限度地发挥这种组合的效用。诺丁汉大学拥有一个集中的设施，该仪器将位于设备访问和重要的专业知识，为内部和外部的学术研究提供。该仪器将促进内部学术研究项目，包括EPSRC高级治疗和纳米医学博士培训中心、碳捕获和储存中心、清洁化石能源中心、可持续化学中心、增材制造中心、3D打印中心和再生医学中心。此外，现有的合作关系将在麻省理工大学和其他国家研究所之间得到利用，从而在制药（阿里斯泰尔·佛罗伦萨教授，斯特拉斯克莱德大学）、再生医学（莫利·史蒂文斯教授，伦敦帝国理工学院）、半导体材料、设备和技术（大卫·伍德教授，达勒姆大学）等领域实现3D材料表征的逐步改变。

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).