Title: A Smart Saliva-based Point-Of-Care biosensor for interactive management of Chronic Obstructive Pulmonary Disease: COPD-SPOC monitor
Funder: Department of Health and Social Care

Abstract: Over a 36-month (M) period, 20 clearly defined work packages (WP) [Gantt chart] will be undertaken to deliver 6 objectives: Objective 1: A dedicated expert by experience forum, including 6 COPD patients, will actively buddy the researchers in an iterative process throughout design, development and refinement of the saliva sampler, monitor and interactive platform [M1-30]; linking into particular work packages e.g. WP5, 6, 7, 9 and 11. Input will involve a series of steps e.g. sketch displays/prototypes. Healthcare professionals/providers will also be engaged for scoping the monitor s position within the COPD care pathway. Objective 2: The fully functional COPD-SPOC monitor incorporates: A magnetometer system to quantify binding of magnetic particles to the sensor surface for 3 target biomarkers. An assay reaction vessel/consumable containing the chemical components to measure salivary levels of CRP, PCT and NE. This docks into magnetometer system for measurement. A saliva collector, also transferring sample to reaction vessel. In collaboration with specialised subcontractors with proven track-record in biomedical-diagnostic instrumentation, the activities for developing each component will include: 2.1. Advanced magnetometer development [M1-21] Design and manufacture early prototype 3 coil magnetometer Refine design through laboratory/end-user testing Manufacture refined prototypes Develop Graphical User Interface Signal processing to extract biomarker levels. 2.2. Assay reaction vessel (consumable) development [M1-15] Design and manufacture early prototype consumable Analytical and end-user evaluation Manufacture refined prototype 2.3. Design optimisation and suitability of saliva collection device [M1-15] Design and manufacture early prototype saliva collector End-user evaluation and laboratory testing Manufacture refined prototype 2.4. Assay integration for three salivary biomarkers [M1&ndash;15] Develop protocols to produce paramagnetic particles and surfaces in the consumable with controllable antibody activity Optimise stability of antibody coated sensor surface and particles Adapt assay protocols for microfluidic processes and surfaces in the consumable 2.5. Integration, testing and refinement of complete COPD-SPOC monitor system [M16-35] Demonstrate microfluidic functional compatibility of COPD-SPOC monitor system Demonstrate working assays for the three biomarkers and use on saliva samples with defined concentrations Final Improvements to COPD-SPOC system 2.6. Establishing processes for regulatory approval [M1-M35] Establish regulatory compliant procedures Collection of technical file/user requirements documentation. Objective 3: Effective and engaging intervention in patient self-monitoring will involve: 3.1. Further developing the patient wellbeing diary App [Figs.7, 8] to include patient-clinician bi-directional communication and simple gamification to motivate and educate patients on early exacerbation recognition/treatment compliance [M1-M18]. 3.2. Designing and constructing software for prediction/triage of COPD episodes, based on combining saliva biomarker measurements and patient wellbeing scores [M13-M24]. Objective 4: The complete COPD-SPOC monitor prototype will be evaluated in a community-based study involving 30 COPD patients for 6 months [M25-33]. This will also evaluate the App and the saliva collector. Prototype-measured analyte levels will be compared with results from commercially available kits. Semi-structured qualitative interviews will explore individual patients real experiences; data will enhance quantitative measures of patient utilisation of the system by providing information about patients day-to-day lived experience of monitoring their COPD, together with the reasons for engagement/behaviour. Objective 5: The health economic case and business model will be strengthened by: Incorporating anticipated device/consumable costs and practical scenarios of distribution into our established economic model [M6; M18] to provide assessment of the commercial headroom and device/intervention impact on QALYs and clinical outcome [M24-27]. Refining and updating our previous market research reports from Frost & Sullivan and MediLink WM to fully inform the commercial strategy on competition developments and a fast-changing healthcare landscape. Objective 6: Sound and effective routes-to-market for maximal return on investment and clinical impact will be assured by a purposeful Commercial Advisory Group with distinguished leadership and respected expertise in the commercialisation and exploitation of healthcare innovations.

Lay abstract: Chronic obstructive pulmonary disease (COPD) is the 2nd leading cause of chronic disability and 4th leading cause of death worldwide. Patients have frequent exacerbations, which severely and progressively impair their lung function and quality of life, leading to inability to work and unscheduled GP visits. COPD exacerbations remain the second most common cause of emergency hospital admissions; with 1 in 3 of discharged patients being readmitted within 3 months. Thus exacerbations are important events in a COPD patient s journey and are duly recognised in national and international COPD management guidelines. All recognise that early diagnosis and treatment of COPD exacerbations can reduce their severity and limit the associated lung damage, yet often treatment is delayed because early worsening of symptoms goes unrecognised. The need exists for a simple portable monitor that will allow patients to assess their condition at home and help them spot exacerbations early. To address this need, our team has developed a sensitive analyser which measures 3 substances called biomarkers (C-reactive protein; procalcitonin; neutrophil elastase) in saliva within the appropriate working ranges in less than 5 minutes. We have demonstrated that the levels of these biomarkers vary depending on the severity of COPD inflammation and development of infection, and importantly can give early warning of the onset of an exacerbation. Patients have supported our solution and prefer having saliva tests to blood. This project will now improve efficiency by assembling all 3 biomarker tests into a hand-held COPD-SPOC monitor suitable for home use; simultaneous biomarker measurements will be made on a single small saliva sample (much less than half a teaspoon). As experts by experience , patients will be actively involved in partnership with the research team throughout the design, development and testing stages of the monitor. The team appreciates that clinical usefulness of this monitor also depends on receiving regular information on how the patient feels . Prompted by ideas from our patient focus group, a specific App will be produced to combine the biomarker results with simple health scores recorded by patients using an electronic wellbeing diary. The App will also include interactive facilities for patients to communicate with their clinician and to improve their engagement with self-care and use of the monitor. During the project, manufactured test models of the COPD-SPOC monitor will be evaluated by COPD patients and healthcare professionals within a community setting to inform on the further necessary technical and user-friendly practical refinements. This COPD-SPOC monitor will be the first of its kind in COPD care, providing patients with a personal means of performing regular COPD health checks to help identify and treat exacerbations promptly, whilst still being able to maintain contact with, and receive individual advice, from their clinical team. As such the monitor will enable healthcare providers to offer high quality COPD care based on an innovative self-assessment intervention delivered at point-of-care. This would facilitate the much-needed saving of expensive COPD-associated NHS and global resources, whilst equipping patients with the necessary confidence to make decisions about their own COPD health.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY