High resolution, cryogenic analytical and transfer scanning electron microscope (HR-CAT-SEM)

天然和人造分子材料是许多现代技术的核心，从能量转换和存储设备，推进系统到建筑材料，同时也是日常生活的核心，从食品，保健品和化妆品，到电子设备和纺织品。由于分析科学的最新进展，现在我们知道“分子材料”中存在什么分子，然而，由于大多数分子材料（包括生物物质）表现出高度复杂的异质组成，缺乏远程秩序，结合高度动态/亚稳态特性，我们通常对这些分子的位置只有一个模糊的概念。考虑到材料的所有重要功能特性，包括电子、光子、磁性、催化气体吸收和传输，都是在纳米尺度上出现的，而活细胞的生物功能依赖于在纳米尺度上运行的分子机制，因此开发能够提供任何复杂材料的完整结构信息的新方法至关重要。从单分子到纳米级超分子组装再到三维微尺度结构。目前，在分析技术中，电子显微镜（EM）处于一个独特的位置，可以提供三维形态信息内容，跨越微米、纳米和微长度尺度。然而，在分子材料的背景下，EM方法有两个明显的缺点，与电子束的侵入性有关，电子束在成像时可以迅速破坏材料内的精细分子。此外，电磁在真空条件下工作，与大多数水合材料不相容，包括生物样品，当水被去除时，其天然结构就会丢失。提出的新HR-CAT-SEM平台-包括一个独特配置的高分辨率，低温分析和转移扫描电子显微镜，旨在解决这些挑战，通过使用低能量电子束（低至1keV），同时提供1.6nm的空间分辨率，以进行有效的纳米级分析（通过使用场发射枪（FEG），结合现代高对比度，多模式探测器）；并通过热稳定材料或通过水合样品玻璃化，并使用聚焦离子束（FIB）切片，所有这些都在低温条件下进行，从而能够通过3D多尺度分析来研究以前棘手的材料科学问题。重要的是，诺丁汉开发的冷冻fib切片和冷冻转移协议将在HR-CAT-SEM中实施，将允许跨越长度尺度的旅程；从光学显微镜和扫描电子显微镜（SEM）的微尺度开始，到纳米尺度（fg -SEM）和皮尺度（转移到高分辨率透射电子显微镜HR-TEM），提供迄今为止最完整的复杂分子材料结构理解。此外，HR-CAT-SEM独特的低温转移能力将为相关分析开辟新的领域，其中EM方法获得的结构信息将与二次离子质谱（OrbiSIMS）和x射线光电子能谱（XPS）相补充，从相同体积的材料中提供化学分子组成和分子键的相关信息。如此规模和雄心勃勃的项目之所以成为可能，是因为诺丁汉大学在这一领域拥有丰富的专业知识，以及独特配置的纳米和微尺度研究中心实验室www.nottingham.ac.uk/nmrc， HR-CAT-SEM将被安置在那里，该实验室已经拥有相关分析所需的所有仪器（HRTEM， XPS, OrbiSIMS），在一个屋顶下，以及必要的样品处理基础设施，需要全面有效地实施这个项目。

Natural and man-made molecular materials are at the heart of many modern day technologies, from energy conversion and storage devices, to propulsion systems to construction materials, whilst being also at the core of everyday life, from foodstuffs, healthcare products and cosmetics, to electronic devices and textiles. Thanks to recent advances in the analytical sciences, now we know what molecules are present within "molecular materials", however, due to the fact that most molecular materials (including living matter) exhibit highly complex, heterogeneous compositions, with a lack of long-range order, combined with highly dynamic/metastable properties, often we have only a vague idea where these molecules are located. Considering that all the important functional properties of materials, including electronic, photonic, magnetic, catalytic gas-sorption and transport, emerge at the nanoscale, and the biological function of living cells relies on the molecular machinery operating at the nanoscale, it is critically important to develop new methodologies capable of providing full structural information on any material of any complexity, from single molecule to nanoscale supramolecular assembly to 3D microscale architectures.Currently, amongst the analytical techniques, electron microscopy (EM) is in a unique position to offer morphological information content, in 3D, across the pico-, nano- and micro-length scales. However, in the context of molecular materials, EM methodologies suffer from two significant drawbacks, related to the invasive nature of the electron beam that can rapidly damage delicate molecules within materials, whilst they are imaged. Also, EM operates in vacuum conditions, being incompatible with most hydrated materials, including biological samples, the native structures of which are simply lost when water is removed. The proposed new HR-CAT-SEM platform - comprising a uniquely configured High Resolution, Cryogenic Analytical and Transfer Scanning Electron Microscope, is designed to solve these challenges, through the use of low energy electron beams (down to 1keV), whilst delivering 1.6nm of spatial resolution necessary for effective nanoscale analyses (enabled by the use of a field emission gun (FEG), combined with modern high contrast, multi-mode detectors); and by stabilising the material, either thermally or through hydrated sample vitrification, and sectioning using a focused ion beam (FIB), all under cryogenic conditions, thereby enabling the investigation of previously intractable materials science problems, through 3D multiscale analysis. Importantly, the cryo-FIB sectioning and cryo-transfer protocols developed at Nottingham, to be implemented within the HR-CAT-SEM, will allow a journey across the length scales; starting from the microscale, enabled by optical microscopy and scanning electron microscopy (SEM), to the nanoscale (FEG-SEM), and picoscale (transfer to high resolution transmission electron microscopy HR-TEM), delivering the most complete structural understanding of complex molecular materials to date. In addition, the unique cryo-transfer capability of the HR-CAT-SEM will open up new horizons in correlative analysis, where structural information obtained by EM methods will be complemented by secondary ion mass spectrometry (OrbiSIMS) and X-ray photoelectron spectroscopy (XPS), providing correlated information on chemical molecular composition and molecular bonding, from the same volume of material. A project of such scale and ambition is made possible due to the rich expertise in this area available at Nottingham, and the uniquely configured Nanoscale & Microscale Research Centre laboratories www.nottingham.ac.uk/nmrc, where the HR-CAT-SEM will be housed, that already hosts all the instruments necessary for correlative analysis (HRTEM, XPS, OrbiSIMS), under one roof, along with the necessary sample handling infrastructure, required for full, effective implementation of this project.