Light is essential for life. For example, light is key to photosynthesis and vision. Light is also important in technology, such as in nanoscale optoelectronic devices. Developing a molecular-level understanding of light-induced processes is crucial for the rational design of new light-activated materials to address important challenges currently facing society, such as harnessing solar energy efficiently and developing new tools for disease diagnosis and therapeutics. Our vision is to establish a unique, state-of-the-art, laser facility providing femtosecond light pulses with a wide range of energies, from the infrared (IR) to the vacuum ultraviolet (VUV), housed in a £2M purpose-built, environmentally-controlled, stable basement laboratory. We will exploit this facility to improve our fundamental understanding of light-induced processes by using a bottom-up approach to study systems across the complexity scale, from isolated gas-phase molecules to proteins, nanoparticles, soft materials and solids, for applications ranging from bioimaging and therapeutics to solar energy materials. This will be achieved using a single spectroscopic technique, time-resolved photoelectron spectroscopy, in molecular and ion beams, liquid-microjets and surfaces, complemented by femtosecond transient absorption spectroscopy, femtosecond stimulated Raman spectroscopy and multi-photon microscopy.

Two-photon microscopy is a leading-edge imaging technology and a powerful research tool that combines long wavelength excitation and laser scanning microscopy. Of importance to our work it can enable capture of high resolution three dimensional images of living cells within 3D constructs as well as in-depth penetration of specimens tagged with very specific fluorophores. This technology is now becoming a method of choice for the dynamic imaging of biological and polymeric systems, not otherwise possible by other optical approaches and therefore will underpin a broad number of research programmes in biomaterials and tissue engineering.

The world's population is rapidly growing and, most importantly, at the same time is ageing. This provides a driving force for the increase in cancer, which is predicted to grow from 18.5M in 2018 to 29.5M in 2040. One of the most effective strategies to combat cancer has been the introduction of screening programmes, which enable the disease to be detected at an earlier stage when it is curable. Earlier stage disease also lends itself to minimally invasive and endoluminal surgery, with advantages in terms of reduced morbidity and better preservation of normal function. There is an acceptance that the use of minimally invasive and endoluminal surgery will continue to grow, perhaps in conjunction with robotic-assistance. But, to deliver this ambition, appropriate surgical tools need to be developed. This includes tools for real-time diagnosis of cancer that can be coupled with ablative and excisional modalities to eradicate the disease. Combined diagnostic and ablative tools will enable microscopic disease to be detected, particularly at cancer margins where infiltrative growth is difficult to distinguish from normal tissue. Failure to eradicate such microscopic disease is usually the cause for treatment failure and cancer recurrence. Our multidisciplinary team of physical scientists, engineers, laser specialists, and clinicians have begun to address this shortfall in surgical hardware precision by investigating a new laser-based approach ideally suited for minimally invasive and endoluminal cancer surgery. By employing "ultrashort" picosecond lasers, that deliver energy in a series of pulses only a few picoseconds long, we have demonstrated the ability to remove (ablate) tumours on a precision 2 orders of magnitude smaller than existing tools. Importantly, because the laser pulses are so short, there is no time for heat to diffuse into surrounding tissue, as is the case for existing surgical tools. Therefore, we have shown that damage to tissue around the surgical zone can be restricted to less than the width of a human hair - almost on the scale of individual cells. On clinically relevant tissue models we have demonstrated in the laboratory that this picosecond laser ablation could provide a step change in precision resection of the bowel and hence transform endoluminal colorectal cancer surgery. Additionally, we have shown that ps laser pulses can be flexibly delivered via novel hollow core optical fibres giving confidence that endoscopic deployment can be realised and opening up new areas of minimally invasive procedures. We now need to capitalise on this foundation and have therefore expanded our network of clinical expertise and identified new areas where our technology could be truly transformative. Neurosurgery is the ultimate test of precision, even microscopic loss of healthy tissue can have a huge impact on quality of life. In head and neck surgery, minimising resection of normal tissue allows functional preservation of speech and swallowing, positively influencing quality of life outcomes. In parallel, we aim to build on our successful results in colorectal cancer by developing novel strategies for incorporating real-time diagnostic imaging aiming towards clinical application. The proposal will take our understanding of lasers in colorectal cancer surgery towards clinical application, whilst simultaneously exploring new areas of application (Head & neck and brain cancer) where the technology is also thought to have huge potential benefit.

Hollow core optical fibres guide light in a hollow (usually, gas-filled) core rather than in a solid glass core as in all conventional fibres. The use of a hollow core means that many of the constraints on optical fibre performance which are due to the properties of the core material are lifted (often by many orders of magnitude) and the fibres can by far outperform their more familiar conventional counterparts. There is a problem, however: how can you trap light in a hollow core? Substantial effort has been put into developing so-called photonic bandgap fibres over the last 20 years. These fibres rely on a complex cladding structure to trap light in the hollow core with low losses. They have been developed to a high degree but have been held back by some apparently insurmountable practical problems. These have especially constrained their performance at the short wavelengths which are important in many applications such as high precision laser machining and materials modification. The state-of-the-art laser systems can now deliver the necessary radiation for these applications: however, a truly flexible delivery system does not currently exist. This ability to deliver the pulsed laser light flexibly from the laser system to the point of application is a key advance required to develop practical and commercially viable applications. Over the last eighteen months, researchers in this collaboration and at a couple of other laboratories across Europe have demonstrated that a much simpler fibre design can actually be far more effective than the bandgap fibres. This is especially true at long wavelengths (in the mid-infrared) and at short wavelengths (eg 1 micron wavelength and below.) Numerical simulations now suggest that these designs can be extended to offer the possibility of their outperforming any existing optical fibres at almost any optical wavelength. This proposal is to demonstrate these fibres at a range of short wavelengths and to work with four UK-based companies to establish them as useful in manufacturing and clinical environments. This involves making fibres with several designs, verifying their performance, identifying the barriers to their use and overcoming them, and then working in the laboratories of our collaborators to establish them as useful on the factory floor and also in medical and engineering measurements. Along the way, we aim to demonstrate the lowest-loss optical fibre ever (at a longer wavelength) and to investigate whether these designs can be extended to deliver laser beams with low beam quality.

Ti:sapphire lasers set the standard for precision in instrumentation. However, commercial systems are bulky and complex to make, due in large part to the requirement for a painstakingly manufactured pump laser. The potential exists to replace these complex pump lasers with mass-produced, compact, and inexpensive diode lasers if we can unpick the physics of the light-matter interactions that govern the efficiency. This programme will lead to a step-change in our understanding, allowing us to redesign Ti:sapphire lasers from the ground up, tailoring them for diode-pumping and enabling high-end applications beyond the laser lab, initially in portable quantum technologies and analytical instrumentation. This project will - - Fully describe the underlying physics of pump-induced losses in Ti:sapphire crystals for the first time. - Initiate the development of a manufacturable, platform laser technology with the performance of Ti:sapphire but the practicality of diode-pumping. - Identify the combinations of diode-laser and Ti:sapphire crystal specification required to maximise both the wall-plug efficiency and manufacturability of Ti:sapphire lasers. - Develop exemplar narrow-linewidth and dual-comb demonstrators for future development towards applications in optical clocks and combustion analysis. The investigator team for this project brings together the grouping that demonstrated the first diode-pumped Ti:sapphire laser with experts in narrow-linewidth lasers for quantum technologies and laser spectroscopy for combustion analysis. The project partners include one of the world's leading manufactures of high-specification lasers (Coherent Scotland), the world's leading manufacturer of Ti:sapphire crystals (GTAT Corporation), a high-power visible diode-laser systems manufacturer (Arctos Lasertechnik), and the UK National Quantum Technologies Hub for Sensors and Metrology. An advisory panel of representative for these organisations, together with experts on technology transfer in the manufacturing of lasers and industrial gas-sensing, will provide the investigator team with strong industrial guidance and a route to accelerate economic and societal impact.