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

Lead Research Organisation: University of Nottingham


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.

Planned Impact

By its very nature, HR-CAT-SEM will contribute to advancements across a broad spectrum of disciplines: Chemistry, Pharmacy, Materials Science, Food Science and Biology. In addition, this instrument will continue to facilitate on-going investigations across a wide range of more traditional inorganic materials science problems, at high spatial resolution, e.g. metal oxide nanocomposites for the aerospace industry (Engineering) and semiconductor device structures for the optoelectronics industry (Physics/E&EE); soft organic materials, biological cell interactions with porous scaffolds and orthopaedic implant materials (Engineering/Pharmacy); and nanostructured materials for hydrogen storage applications and nanocatalysis (Engineering/Chemistry); reaching the widest cross-section of the UK economy. Hence, HR-CAT-SEM will open up pathways to impact across a wide range of challenging material systems, of immediate importance to the Oil & Gas / Geochemical, Polymer, Food & Pharmaceutical industries. Each of the team of 14 investigators on this proposal have established active industrial collaborations with UK companies covering these sectors, which will ensure immediate impact of HR-CAT-SEM on the UK economy.

The Steering Group of the nmRC, consisting of representatives of all five Faculties of UoN, will work closely with UoN's Research and Innovation group (R&I) to manage collaborations with industrial partners, knowledge exchange, and the commercialisation of future research. A representative from R&I will sit on the nmRC Steering Group, to ensure that industrial collaborations are managed efficiently and that research outcomes are maximised. R&I have staff dedicated to the energy, aerospace and pharmaceutical sectors and both the management and users of the nmRC will work closely with these experts. For example, the development of innovative techniques in the cryogenic sectioning and transfer of materials across FIBSEM, TEM and SIMS platforms creates potential for future collaborations with companies in the Judges Group (11 scientific and engineering companies all based in the UK). Currently, the nmRC runs active partnerships with > 40 companies that require FIB, SEM and TEM analyses (methods at the core of HR-CAT-SEM), such that HR-CAT-SEM can be applied immediately to a range of industrial challenges, building on existing services-rendered work carried out at the nmRC for precision engineering, aerospace, energy, food science, and the medical and geological sectors, e.g. Rolls-Royce, EoN, Smith & Nephew and Juniper Pharmaceuticals, that require HR-CAT-SEM capabilities.
Description The HR-CAT-SEM system has been demonstrated as a versatile and powerful tool for nanoscale analysis for a wide range of materials from batteries to foodstuffs. There are two publications, with several more in the pipeline
Exploitation Route Methodologies and workflows, especially for cryogenic analysis at nanoscale are being applied to a variety of research problems across Engineering and Physical Sciences (see publications) with several case studies being written up at the moment.
Sectors Agriculture, Food and Drink,Energy,Healthcare,Pharmaceuticals and Medical Biotechnology,Other

Title High-Resolution Cryogenic & Analytical Transfer Scanning Electron Microscope 
Description HR-CAT-SEM - high resolution, cryogenic analytical and transfer scanning electron microscope - is both a revolutionary concept in materials characterisation and a unique piece of instrumentation equipped with state-of-the-art, cryogenic, focused ion beam (FIB), field emission gun (FEG), environmental scanning electron microscope (SEM), cryo-transfer stage, energy dispersive X-ray spectroscopy (EDS), an electron backscattered diffraction (EBSD) detector, a scanning transmission electron microscopy (STEM) detector, a cryo-micromanipulator, an in-situ plasma cleaner and an optical microscope. This uniquely configured instrument will take you on a journey across the length scales, starting with optical imaging at the microscale that allows quick identification and marking of exact areas of interest in the material in its native form (i.e. at room temperature and pressure, in liquid environment or on surfaces under ambient conditions) and real-time imaging of any dynamic phenomena taking place in materials or living cells. Next, cryogenically stabilised material with all its intrinsic features and composition preserved will be etched, milled and drilled with the FIB whilst imaged by the FEG-SEM with a resolution of 2 nm, thus revealing 3D nanoscale structures of cells, particles, films, plants, gels, emulsions etc. A powerful combination of detectors (EDS, EBSD and STEM) will complement the high resolution imaging in direct space by providing nanoscale analytical information, such as maps of chemical elements and crystallographic data, allowing elucidation of inter-atomic bonding and inter-molecular interactions within the material. Finally, a cryo-micromanipulator will perform a site-specific lift-out of a thin lamella of the material for transmission electron microscopy (TEM), secondary ion mass spectrometry (SIMS) and X-ray photoelectron spectroscopy (XPS), all under cryogenic conditions, delivering picoscale structural and chemical information about the material, down to a single atom. 
Type Of Material Improvements to research infrastructure 
Year Produced 2021 
Provided To Others? No  
Impact The new imaging and analysis tool HR-CAT-SEM is currently in development, and is expected to be launched in latter half of 2021, and made available to UK research community. 
Description ZEISS Research Microscopy Solutions 
Organisation Carl Zeiss AG
Country Germany 
Sector Private 
PI Contribution This is a nascent partnership with Zeiss is set to develop, commission and utilize the unique HR-CAT-SEM capability at University of Nottingham.
Collaborator Contribution Zeiss company engineers and specialists are now working closely with the Nanoscale & Microscale Research Centre (nmRC) at Nottingham to build a bespoke system for correlative imaging and analysis from micro to nano to atomic scale.
Impact we are in a process of signing a collaboration agreement and setting up the equipment.
Start Year 2020
Description Creation of image for social media engagement / promotion of the Nanoscale and Microscale and Research Centre (nmRC) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The Crossbeam 550 was used to etch a St Valentines message onto a substrate. This was distributed via social media (Twitter and LinkedIn)
Year(s) Of Engagement Activity 2023
URL https://twitter.com/UoNnmRC/status/1625508279588618246
Description Creation of marketing materials for Nano Prospectus 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact The HR-CAT-SEM (Crossbeam 550) was used to etch a logo and QR code onto an apple seed that linked to the University's nano-prospectus. A short video was produced and this was distributed via social media (Tiktok) https://www.tiktok.com/@uniofnottingham/video/7076472928950373637?is_copy_url=1&is_from_webapp=v1
Year(s) Of Engagement Activity 2022
URL https://www.nottingham.ac.uk/isac/news-items/nano-prospectus-on-a-bramley-apple-seed.aspx
Description Royal Microscopy Society Virtual Cryo-EM Course 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact This was a 4-day virtual course covering both theory and practical elements of cryogenic electron microscopy techniques as typically applied to scientific or commercial research. A series of lectures and question-answer sessions were complemented by live and pre-recorded demonstrations to a global audience from academia and industry.
Year(s) Of Engagement Activity 2021
URL https://www.rms.org.uk/rms-event-calendar/2021-events/all-things-cryo-a-virtual-course.html