In this research, I will develop a cyber-physical system (CPS) for the diagnosis and treatment of lung diseases. My project is motivated by three facts: 1) Lung cancer treatment is most successful when it is found at an early stage. Treatment of early-stage cancer offers 73% chance of survival, whereas in late-stage this is reduced to 13%. However, the current methods for early diagnosis of peripheral lung lesions using bronchoscopic biopsy are challenging with varying diagnostic yield. Thus, there is a need to develop new technologies for reliable diagnosis of cancer in the lung periphery. 2) At present, surgical resection of malignant nodules (Tumours<3cm diameter) in the lung is the treatment modality of choice. However, most patients are not suitable surgical candidates, thus prompting the need for other therapeutic options. An emerging less invasive treatment option is bronchoscopic ablation of lung cancer via delivering physical therapy to lesions in the lung (cryotherapy/photonic ablation). Bronchoscopic ablation is not widely used to treat lung cancer, primarily due to the limited depth of penetration and small range of motion of the bronchoscope. 3) The overall in-hospital mortality rate for patients in ICU with ventilator associated events approaches 30%. New pulmonary infiltrates are a diagnostic challenge and due to the poor sampling methods available, patients are often initiated on non-targeted therapies. Bronchoscopy and sampling of the distal lung in diffuse diseases is not standardised and lacks repeatability and requires expert operators. The key aim of this research is to democratise ICU bronchoscopy and develop a platform using vision computing, EMT and external registration to enable non-skilled operators to sense, sample and diagnose pathology in vivo in situ. To this end, I propose a CPS that addresses the unique issues of bronchoscopic diagnosis and treatment of lung diseases using novel mechatronic systems, control algorithms, and image guidance. The CPS has the potential to deliver unified diagnosis and treatment platform for early-stage lung cancer and on-site differential diagnosis of diffuse lung diseases by enhancing the current bronchoscopic technology in two specific ways: 1) Manipulation augmentation: I will design and develop a mechatronic device comprised of an active mini-bronch and a user interface for steering. The active mini-bronch is made of a flexible robot equipped with an endoscopic camera, fibre-optics for molecular imaging/sensing of tissue. It also provides a working channel that can be used for ablation of cancerous tissue or tissue sampling. The proposed mechatronic device can be used in two scenarios: (1) Autonomous tissue sampling in intensive care units: The mini-bronch uses control algorithms to navigate to lung subsegments and take multiple samples for diagnosis, (2) Semi-autonomous tissue diagnosis/treatment: the operator uses the user interface to navigate the mini-bronch to the periphery of the lung, characterise, sample and detect cancerous tissue, and then ablate . My control algorithms will provide unprecedented capabilities in terms of dexterity, safety, and ease of operation. 2) Visual augmentation: A key goal is to develop algorithms that employ emerging molecular imaging techniques to provide an imaging technology for in-vivo diagnosis of lung diseases. I postulate that the proposed CPS will enable rapid on-site evaluation of lung diseases and successful bronchoscopic detection and therapy.

The unique properties of light have made it central to our high-tech society. For example, our information-rich world is only enabled by the remarkable capacity of the fibre-optic network, where thin strands of glass are used to carry massive amounts of information around the globe as high-speed optical signals. Light also impacts areas of our society as diverse as laser-based manufacturing, solar energy, space-based remote sensing and even astronomy. One area where the properties of light open up otherwise-impossible capabilities is medicine. In ophthalmology for example, lasers are routinely used to perform surgery on the eye through corneal reshaping. This involves two different lasers. In the first step, a laser producing very short pulses of infrared light cuts a flap in the front surface of the eye to provide access. In the second step, another laser producing longer pulses of ultraviolet (UV) light sculpts the shape of the cornea and correct focusing errors. The flap is then folded back into place so that the cornea can heal. The two very-different laser systems in that example illustrate an important point: the effects of light on human tissues are highly-dependent on the specific properties of both the light and the tissues involved. To sculpt the cornea, the laser wavelength of 193 nm is in the deep UV region of the electromagnetic spectrum, much shorter than the visible range (380 - 740 nm) we are familiar with. This is because (unlike visible light) it is very efficiently absorbed by the cornea, so that essentially all the energy of the light is deposited at the surface. Thus only a very thin layer of tissue (a few microns thick) is removed, or "resected", with each pulse of light, facilitating very-precise shaping of the cornea and accurate adjustment of its focusing properties. 193 nm light can be generated by an ArF excimer gas laser, a >40 year-old technology producing a poor-quality low-brightness beam of light. This is suitable for corneal reshaping, but not for a range of other important therapies requiring higher-quality deep UV beams. Unfortunately, alternative ways to generate such short wavelengths are non-trivial, resulting in complex and expensive laser systems not suitable for widespread clinical uptake. U-care aims to address this gap by exploiting cutting-edge techniques in laser physics. We will develop new sources of deep UV light which will be highly compact, robust and low cost. We will develop ways to deliver this light precisely to tissues, and work to understand in detail the biophysical mechanisms involved. Our efforts will focus on new therapies that target some of the biggest challenges facing medicine: cellular-precision cancer surgery, and the emergence of drug-resistant "super-bugs". Importantly, U-care will involve engineers and physical scientists working in close collaboration with clinicians and biomedical scientists to verify that the therapies we develop are effective and safe. By doing so in an integrated manner, we will drive our deep-UV light therapies towards healthcare impact and widespread use in the clinic by 2050.