Multiscale characterization of complex materials using a combination of atomic force microscopy and optical coherence tomography

Newcastle University (NCL) has a history of multidisciplinary collaborations in investigator-led research projects and in largescale, strategic initiatives such as the EPSRC Frontier Award (Oct 2013-June 2019, which involves researchers from four different schools within Newcastle University).
The NCL capital equipment strategies are designed to ensure long-term access to equipment and computing facilities that support our diverse research needs from routine characterisation to state-of-the-art technique development. We recognise that sharing of scientific equipment between Newcastle and widely across the N8 partner universities (eight most research intensive Universities in the North of England) brings multiple benefits, including increased utilisation, greater collaboration, enhanced sustainability and a wider range of facilities available to our researchers.
We have identified the proposed equipment that are required to underpin research in ESPRC priority areas in Materials Characterisation, Functional Materials, Engineering for Life and Health, Engineering Science, Water, Synthetic Biology, Regenerative Medicine, and Nanomedicine. This will benefit multiple research groups across NCL as well as external users both academic and industrial. It supports a portfolio of existing EPSRC grants and brings new capabilities to enable new scientific discoveries. A brief summary of the equipment requested and their functions are as follows:
1). A cutting-edge AFM integrated with microfluidics, allows unprecedented possibilities for exciting applications in single-cell biology and nanoscience, thanks to the precise force control provided by the AFM and the microfluidics capabilities. The capability of high resolution and high accuracy imaging and mechanical measurements supports a range of projects in chemistry and at its interfaces with biology, physics and chemical engineering. It is complemented by the existing state-of-art high resolution surface chemistry analysis techniques available at Newcastle.
2). An optical coherence tomography (OCT) uses infrared light to provide surface profiles and subsurface structures, delivering higher resolution and faster images than ultrasound inspection. When used together with the custom built air-pulse system, OCT also enables characterisation of elastic properties of materials such as biofilms and soft tissues.
Items AFM and OCT together with the existing facilities at Newcastle permit mapping of 3D geometry and mechanical characterisation from sub-nanometer to millimetre scale. This asset enables the study of physical and dynamical properties of soft matter, facilitating investigations of disease progression at subcellular, cellular and tissue levels which will allow formulation of effective diseases diagnosis and treatment strategies. The multiscale quantitative measurement obtained by this asset can also provide datasets needed for constructing predictive models in healthcare and water engineering. As a consequence, it can underpin a range of academic and industry-focussed projects in marine biofilms, biological wastewater treatment, biofilm infections, tissue engineering, cancer research and many other healthcare related applications.
Such multiscale physical and mechanical characterisation capability can be further reinforced by the advanced surface chemistry analysis facilities hosted at Newcastle, which will give rise to world-leading research in materials characterisation. It will enhance the UK as a world leader in a wide range of academic research areas, including engineering, materials, physics, chemistry, biology and medicine.

The AFM enables high resolution imaging and measurement of nanoscale viscoelastic properties, characterising cell-cell interactions and cell-materials interaction, as well as single cell manipulation and experimentation. The custom designed OCT-air-pulse system would enable rapid imaging of surfaces and structures as well as measurement of viscoelasticity of materials at mesoscale. The combined assets of AFM and OCT enable multiscale surface and mechanical characterisation for a vast catalogue of materials. This will not only add substantial value to our multiscale understanding of biological (from single cell to cell communities) and engineered systems, but will also provide datasets for model calibration and validation for multiscale material and biological modelling. Together, these have the capability to benefit material design and predictive models for disease progression.
Therefore, the assets of AFM and OCT are technologies with potential for high societal and economic impact enveloping a large number of themes, such as 1). Well-being and longevity of society: Cancer diagnostics market is estimated to be $13.1 billion by 2020. AFM is used as mechanical marker for disease progression (e.g. cancer) and tissue injury, as well as monitoring how novel drugs affect cellular structures and mechanics. The cell injection capability also enables early stage testing of novel nano-medicines; 2) Water and environment: waterborne infections are estimated to cost over billions of dollars worldwide. The custom modified OCT will be employed to monitor how dispersion agents like disinfectants affect pathogenic biofilms structures and their mechanics; 3) Energy and Sustainability: Battery materials and biosensors market are worth $11.3 billion and $27.06 billion, respectively. AFM equipped with Kelvin probe can serve as a quality control tool for studying the integrity and reliability of battery materials and bio-sensors (e.g. graphene sensors). 4) Manufacture the Future: AFM's nanolithography (nanoscale or submicroscale 3D printing) enables cost effective prototyping strategy. AFM is capable of detecting manufacturing defects on surfaces; while OCT enables rapid imaging of surface of the manufactured products. Together, AFM and OCT can be used as quality control measures for subcomponents in microsystems and larger scale engineering systems.
Such advances of the proposed AFM are likely to have clear benefits on patient outcomes and for healthcare providers and fits within the strategic priorities of the EPSRC challenge theme on Healthcare Technologies. For example, the mechanical biomarker obtained by AFM can help diseases diagnosis and guide the therapists to choose optimised treatment for given stage of disease. Measurement of mechanics of cells and biofilms is a step towards diagnosing and combating diseases. The advanced surface mapping enables development of novel quality control techniques for present and future materials, thereby moving design, manufacturing and engineering forward.
Impact will also be achieved through the training of doctoral and post-doctoral researchers on the equipment who will take these skills into academia and industry, thereby fostering future leaders in an important technology area. This helps to mitigate the 'graduate drain' that is a particular problem in North East England. The presence of these facilities will also strengthen existing industrial partnerships and enable new ones, further contributing to the strength of the regional economy. The actions taken to facilitate these industrial links are described in the Pathways to Impact section.