Combining snake-like robot with wireless electrical-molecular signalling to tackle cholangiocarcinoma

Cholangiocarcinoma (CCA) affects 3000 people in the UK each year, with a dismal prognosis: only 13% of patients survive 3 years. CCA arises in the bile duct, which is a narrow tube with a diameter of about 6mm. As the cancer grows inside, the bile duct is further narrowed and routine scans cannot confirm if the narrowing is due to inflammation or the cancer. Diagnosis relies on the microscopy of samples taken from the narrowed area, but, when narrowed or blocked, it is even harder to obtain samples. In addition, CCA tissue is spatially variable with different areas being genetically different which accounts for resistance of CCA to drug treatment. Moreover, insertion of devices for the diagnosis and mapping of the narrowed bile duct (biliary stricture) must be combined with biliary drainage (stent insertion) to reduce the risk of complications such as infections. Our vision is to bring expertise from multiple disciplines together to develop a new technology with enhanced dexterity to navigate the biliary stricture, develop capabilities for tissue molecular mapping, and create capability to deliver treatment with greater precision. This is expected to then lead to improved survival and quality of life outcomes for patients with CCA. We aim to (a) develop the first ultra-slender snake-like robot to navigate the bile duct and obtain a 3-D mapping (b) deliver nanoparticle based new treatment to the narrowed segment due to cancer and (c) correlate the mapping of the bile duct with the molecular patterns in surgically-removed patient CCA tissue. To address the combination of challenges in both diagnosis and treatment we bring together expertise from medicine, endoscopy, engineering, robotics, imaging, bioelectrics and genomics. The proposed research will be carried out in 4 interdependent work packages (WP). In WP1, a snake-like robot carrying an imaging device that can navigate to the narrowed bile duct will be developed. This will be inserted into the narrowed area of the bile duct (in CCA tissue removed from patients during standard surgical cancer treatments) and take 3D pictures. In WP2, we will create nanoparticles which will be loaded on to the stents that are usually used to open bile ducts blocked due to CCA. These nanoparticles are taken up by the cancer cells. When a wireless electrical field is generated in the vicinity, the nanoparticles stimulate the death of cancer cells. WP3 involves the clinical characterisation of patients with CCA including assessment of their cancer using different types of imaging and tests. These images will be used by WP1 to inform the design of 3D bile duct models/dummies in which we will test the snake robot. In addition, samples from the cancer will be used in WP2 laboratory experiments to assess biological properties and process of cell death in CCA cells. We will create a database and tissue bioresource to characterise variability in CCA types. We will also use CCA tissue resected during surgical treatment to evaluate devices designed and developed in WP1 and WP2. WP4 will co-ordinate and integrate activities across disciplines and WPs to maximise shared learning across the team and deliver the work proposed. This cross-disciplinary approach will provide a new understanding of CCA, innovative tools to secure an accurate diagnosis and a novel approach to its treatment, ultimately leading to dramatically improved outcomes.