Title: Design and optimisation of a Saliva-based Point-Of-Care bioSensor for non-invasive monitoring of COPD exacerbations: COPD-SPOC sensor
Funder: Department of Health (England)

Abstract: Over the 30-month (M) period, we will undertake the following tasks to meet the objectives listed above: Objective 1 : - 1.1. Expand end-user and expert interaction (M1-M29) with multiple exchanges between team members and patients/ experts for feedback including practicalities of testing, device design, anticipated barriers to adoption. - 1.2. Extend literature review (M1-2) and refine market evaluation (M13-M18) to expand knowledge on point-of-care technologies and niche markets. This will augment our preliminary Frost & Sullivan report, establishing an informed commercial strategy for the COPD-SPOC sensor against existent competition/ pipeline developments and a fast-changing healthcare landscape. Objective 2 : - Conduct a community-based patient study (M4-M26) for longitudinal recording of saliva C-reactive protein (CRP), procalcitonin (PCT) and neutrophil elastase (NE) levels alongside a personal event diary in 40 COPD patients with a history of frequent exacerbations. As dynamic changes from stable --> exacerbation --> recovery phases are captured and quantified, findings will determine saliva biomarker utility and practicality in predicting exacerbation onset and evaluating treatment response. Biomarker levels measured by commercial ELISAs will be correlated to patient-defined events; results will inform software development for diagnostic algorithms Saliva samples will also be utilised for validation of the new magneto-immunoassay. Objective 3 : The team, in collaboration with Sarum Biosciences, will undertake: - 3.1. Saliva assay development and validation (M1-18) for each target biomarker. This phase will identify parameters critical in design of the detection chemistry for an accurate diagnostic system. For each analyte, we will: Screen antibodies, magnetic beads and reagent set using optical techniques to observe magnetic bead binding to sensor surface, allowing rapid identification of the optimal reagent set. (1 month). Once the optimal bead-antibody combination has been identified, assays will transfer to the magnetic detection system for further development and optimisation. Dose-response curves will be constructed using ‘healthy’ saliva samples spiked with a range of target analyte dilutions (3 months). This will establish assay sensitivity and detection limits. Once optimised, the assay will be validated against commercial ELISA kits using archived saliva samples. (2 months). Assays will be developed largely sequentially, but with as much parallelism as possible. Planned phasing for CRP: M2-M7; PCT: M8-M13; NE: M13-M18. - 3.2. Development of the prototype magnetic sensing platform . Validated assays will be combined within a detection bench-top prototype system for rapid simultaneous measurement of saliva CRP, PCT and NE. Tasks include: Design to incorporate (a) saliva sample input into a minimum volume sample container (~100 microlitres) and (b) a magnetometer with the required sensitivity to detect target analytes at the required level ( Manufacture and test the combined chip / sample input unit (M3-M5) Manufacture and test the electronics for the magnetometer and voltmeter integrated into a single bespoke unit (M3-M7) Production of a PC with software for control of the magnetometer unit, signal conditioning of the magnetometer signals and data analysis. (M7-M12) Further development and refinement of the platform will continue during M13-M29. -- 3.3. Testing of COPD saliva samples with the magnetic sensing system (M19 - M29). A selection of patient samples will be used; for example single patient samples exhibiting disease-induced wide fluctuations in analyte levels. This allows testing for factors such as cross reactivity between components; disease-induced effects of different viscosities and mucin compositions. Magneto-immunoassay results will be compared with results obtained by conventional ELISA kits. Objective 4 : - Incorporate anticipated device costs and clinical scenarios of distribution into a COPD economic model we have already started to construct with Prof. Richard Lilford’s team, Birmingham University (M22-27). This will determine the commercial ‘headroom’ and device impact on QALYs and clinical outcome.


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