The mid-infrared band of the electromagnetic spectrum has huge potential in healthcare technologies. Many biological molecules exhibit very strong absorption of radiation (light) in this region. This absorption depends strongly on matching the wavelength (colour) of the light to the stretching of the molecular bonds, unique to each molecule. For example, water absorbs radiation at a mid-infrared wavelength of 2.94 um nearly 100,000 times more strongly than a near-infrared wavelength of 1 um. A laser is an intense, highly directional, and monochromatic beam of radiation. The potential of mid-infrared lasers at 2.94 um as medical tools was recognised early on, due to the high-water content of biological tissue (>70%). Focussing a 2.94 um laser on tissue results in highly efficient absorption of the radiation in a very localised area. The subsequent rapid heating in this area causes the tissue to vaporise into a gas (ablation), resulting in an ultra-precise method of removing tissue, e.g. for use as laser scalpels or biopsy replacements. There are, however, a lack of ultrafast mid-infrared lasers with pulse durations shorter than 1 nanosecond (a billionth of a second) suitable for tissue ablation. Existing ultrafast mid-infrared commercial lasers do not have enough energy to initiate ablation, are often too large and complex to be deployed outside of specialist laser laboratories, or have poor beam qualities leading to large beam sizes on the sample (poor spatial resolution). As a result, the standard approach to 2.94 um tissue ablation is to use more widely available lasers (Er:YAG/Nd:YAG OPO) with longer pulses. However, the effect of these longer pulses on tissue can be highly problematic, causing tissue carbonisation (burning) and necrosis (cell-death) in surrounding cells, which can be avoided when using picosecond (ultrafast) pulses. In this project, I will create a compact, robust, fibre-integrated picosecond mid-infrared laser (fPIRL) platform. The platform will be based on a novel cascaded nonlinear wavelength conversion scheme, employing a combination of advanced fibre optic technology and new mid-infrared materials to create a completely fibre-integrated source suitable for wide deployment in non-specialist laboratories and clinics. The fPIRL platform will be employed as an ultra-precise laser scalpel, removing minute volumes of tissue for subsequent analysis with mass spectrometry. The tool will be much less destructive and much more precise than existing techniques. The team assembled crosses industry and academia, including materials scientists, laser physicists, analytical chemists, and systems medicine specialists. Together, we will enable significant advances in various biomolecular analysis techniques. The proposed single-cell resolution molecular mapping setup will help drive improvements in cancer tumour removal surgeries. Our fibre-delivered source will underpin future robotic surgical interventions in hard-to-reach surgical sites. With our long-wavelength source (6 um) we aim to reveal different biological fingerprints, improving diagnoses for certain diseases, than with existing ablation techniques. This project will create a new photonics-based healthcare technologies tool. The tool will enable significant advances in disease diagnosis and intervention, through advances in biomolecular analysis techniques suitable for both research and in-vivo applications. These advances will ultimately improve patient outcomes in the UK for the NHS, leading to a healthier, happier, and more productive society. Beyond this project, the fPIRL could be used for any precision surgical intervention, cultural preservation in ancient art, and polymer processing for biological implants.

Technologies underpin economic and industrial advances and improvements in healthcare, education and societal and public infrastructure. Technologies of the future depend on scientific breakthroughs of the past and present, including new knowledge bases, ideas, and concepts. The proposed international network of interdisciplinary centre-to-centre collaborations aims to drive scientific and technological progress by advancing and developing a new science platform for emerging technology - the optical frequency comb (OFC) with a range of practical applications of high industrial and societal importance in telecommunications, metrology, healthcare, environmental applications, bio-medicine, food industry and agri-tech and many other applications. The optical frequency comb is a breakthrough photonic technology that has already revolutionised a range of scientific and industrial fields. In the family of OFC technologies, dual-comb spectroscopy plays a unique role as the most advanced platform combining the strengths of conventional spectroscopy and laser spectroscopy. Measurement techniques relying on multi-comb, mostly dual-comb and very recently tri-combs, offer the promise of exquisite accuracy and speed. The large majority of initial laboratory results originate from cavity-based approaches either using bulky powerful Ti:Sapphire lasers, or ultra-compact micro-resonators. While these technologies have many advantages, they also feature certain drawbacks for some applications. They require complex electronic active stabilisation schemes to phase-lock the different single-combs together, and the characteristics of the multi-comb source are not tuneable since they are severely dictated by the opto-geometrical parameters of the cavity. Thus, their repetition rates cannot be optimised to the decay rates of targeted samples, nor their relative repetition rates to sample the response of the medium. Such lack of versatility leads to speed and resolution limitations. These major constraints impact the development of these promising systems and make difficult their deployment outside the labs. To drive OFC sources, and in particular, multi-comb source towards a tangible science-to-technology breakthrough, the current state of the art shows that a fundamental paradigm shift is required to achieve the needs of robustness, performance and versatility in repetition rates and/or comb optical characteristics as dictated by the diversity of applications. In this project we propose and explore new approaches to create flexible and tunable comb sources, based on original design concepts. The novelty and transformative nature of our programme is in addressing engineering challenges and designs treating nonlinearity as an inherent part of the engineering systems rather than as a foe. Using the unique opportunity provided by the EPSRC international research collaboration programme, this project will bring together a critical mass of academic and industrial partners with complimentary expertise ranging from nonlinear mathematics to industrial engineering to develop new concepts and ideas underpinning emerging and future OFC technologies. The project will enhance UK capabilities in key strategic areas including optical communications, laser technology, metrology, and sensing, including the mid-IR spectral region, highly important for healthcare and environment applications, food, agri-tech and bio-medical applications. Such a wide-ranging and transformative project requires collaborative efforts of academic and industrial groups with complimentary expertise across these fields. There are currently no other UK projects addressing similar research challenges. Therefore, we believe that this project will make an important contribution to UK standing in this field of high scientific and industrial importance.