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

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).

Economic Impact

The proposed facility will have a number of direct and indirect impacts upon various sectors of the UK economy. Direct impacts will arise from the use of the proposed facility to conduct contract research by such companies such as Walgreens Boots Alliance and Innospec Ltd to advance their research and development programmes in the healthcare and engineering sector respectively. These advances will be linked to new products and associated additional revenue generation. The facility will also be made available to consultancy companies, such as Juniper Pharmaceutical Services and Aystorm Ltd, who represent a large number of national and international clients in the pharmaceutical and high tech materials sectors respectively. The analytical work performed by such companies will generate direct revenue for the UK economy whilst maintaining the UK's strong reputation in this field.

Indirect impact will be delivered in the form of an enhanced capability for advanced research and development for industry in collaboration with Universities, including Nottingham, and others within the MI group and nationally including The University of Leeds, Durham, Manchester, Imperial, Sheffield and Glasgow. The scope of industrial collaboration is extensive and will utilise existing links to EPSRC funded PhD training programmes and EPSRC Centres for Innovative Manufacturing including those in Advanced Therapeutics and Nanomedicines, Regenerative Medicine and Sustainable Chemistry. These include >80 companies such as AZ, GSK, Innospec, Unilever, Rolls Royce, Dyson Appliance Ltd and Smith and Nephew. Relationships are being built with existing UK Catapult centres, e.g. Chris Herbert of the Cell Therapy Catapult, and will be developed with the Formulation Centre, for which the capabilities of the facility will be applicable to a wide range of industrial research and development needs.

Impact upon Society

The multi-disciplinary spread of the users of the proposed materials characterisation facility impacts many sectors of research, particularly within applied disciplines and as such will impact society in a variety of ways. The capability of the facility to enable research within the fields of pharmacy, tissue engineering and biomaterials will lead to the development of more effective drugs, controlled delivery systems, advanced biomaterials, and regenerative medicine technologies. These will produce improvements in the health and wellbeing of both UK and international society.

Enabling research in areas such as life sciences and pharmacy and engineering, the proposed facility will facilitate research into the development of antimicrobial resistance and antimicrobial resistant materials simultaneously in a true multi-disciplinary approach. Utilising current academic links to industry internationally the impact of the research can be realised and implanted both within the UK and more widely. Further materials science and physics related research areas including those within the field of graphene and semi-conductor research will also be enabled by the proposed ToF-SIMS facility ensuring that the UK remains competitive in state-of-the-art device manufacturing.

In all of the disciplines where the proposed facility will be active, the use of the instrument and the associated data processing will form a significant portion of the training and development of the next generation of research scientists. The use of the instrument in undergraduate projects and University held open days for local secondary schools will provide research experience and inspiration to the younger generation of potential scientists within the UK.