Title: Rapid diagnosis of Urinary Tract Infection in Primary Healthcare
Funder: Department of Health and Social Care

Abstract: To achieve the Objectives (above), the project comprises eleven work packages (WPs), with specific deliverables/ milestones. Four WPs are focused on delivery: Project management (WP1), ethics (WP9), regulatory/ exploitation (WP8) and producing the final report (WP11). Deliverables from these WPs are: a standing agenda (month 2); minutes of management meetings (ongoing); ethical approval (month 5); outline exploitation option plan defined (month 6); exploitation option defined (month 12); review of exploitation implementation (month 30); exploitation dissemination materials (month 36); final report (month 36). Two WPs evaluate clinical validation and integration. Technology in patient and user context (WP2) will inform device design and how it will be integrated into practice. Health economics and clinical pathway development (WP10) will be led by Oxford DEC using early decision analytical modelling. Literature review and expert opinion will be used to establish the clinical pathway for UTI and placement of the device. The model will enable examination of potential cost-effectiveness, and guide product development/ evidence generation for commercialisation and adoption, aiming to influence patient care pathways and gain acceptance of the technology. Deliverables associated with these WPs are: 2.1 expectations, training and communication needs (month 2), 2.2 service expectations (month 6), 2.3 context of use constraints (month13), 2.4 form/function/interface specification (month 16), 2.5 packaging and instruction constraints (month 16), 2.6 usability and amendments based on 'dry run' prototype testing (month 24), 2.7 risk mitigation strategy (month 31); a preliminary report on health economic impact and integration into clinical pathways (month 36). Five WPs will achieve the technical objectives to develop a device and test cartridge to measure three bacteria and IL-8 with rapid turnaround time. Initial studies will validate the inflammatory marker, involving scientific literature review and a laboratory based study (WP3). Knowing the targets for the assays, a 6 month work package (WP4) will define the system design and the integration of fluidic chips, magnetometer, controllers for fluidics and moving opposing magnets, user interface and data handling. A 2 year work package is focused on Instrument design, fabrication and evaluation (WP5). This is divided into two sub-work packages: firstly, development of the magnetometer (WP5.1) which will incorporate multiple coils and opposing magnets along with a cartridge interface. Secondly, the fluidic control for the cartridge (WP5.2) will be developed to enable sample pre-treatment and movement through magnetically suspended particles. Input from WP2 and WP4 will inform development of the magnetometer. Assay and cartridge development (WP6) will commence after validation of the inflammatory marker (WP3). Four assays will be developed for use in a fluidic cartridge (3 bacteria and IL-8). Assay parameters will be determined (WP6.1) including number of particles and antibody concentration. The structure and the fluidic pathways required for the 4 assays will be designed (WP6.2) and early prototypes fabricated for testing and confirming analytical performance. System testing and evaluation will take place in the final year, using patient samples (WP7). The deliverables on the technical WPs are: Report validating inflammatory marker (month 6); System design documents (month12); Assays of bacteria and inflammatory markers defined (month 18); fabricated assay cartridge ready for use (month 24); Report on performance of integrated system and results of patient study (month 36). Some prototype development/ production will be subcontracted to a design consultancy with a suitable quality management system, appropriate for device development to meet regulatory standards; the project team will ensure there will be no duplication of activity between design work carried out for technical WPs and design activities in WP2. Go/no-go milestones; At the end of year 1: Bacteria assay demonstrated. At the end of year 2: Mock up prototype fabricated for use in WP2.

Lay abstract: Urinary tract infection (UTI) is a common and unpleasant problem affecting thousands of people. It leads to painful symptoms and time off work, and sometimes significant complications, such as kidney damage. GPs diagnose UTI in patients based on their symptoms. Often they will also check a urine sample for infecting bacteria, and for white blood cells, which show the patient s body is generating an inflammatory reaction to the infection. Current methods to look for bacteria and inflammation are slow and sometimes unreliable- it can take three days to get a result for a urine sample sent to a microbiology laboratory. As the patient has ongoing symptoms, the GP will sometimes prescribe antibiotics before the result is back. However, if the result received actually shows no infection, antibiotics could be harmful to the patient, and also to the community at large, due to increasing risk of antibiotic resistance. We plan to develop a device which can be used in GP practices to identify UTI bacteria and inflammation in five minutes. The patients will give a urine sample to the practice nurse, who will then put some of the sample into a test cartridge. This cartridge contains antibodies to common UTI bacteria, and a protein we believe will be a better test for inflammation than the current check for white blood cells. When the cartridge goes into the new detection device, the diagnosis will be made. Patient feedback on our plans was received from patient panels supporting the research team through focus groups and direct feedback. This emphasised the importance of ensuring the test is safe, easy to use for nurses, inexpensive for GP practices, and easy to store. We will ensure the device is accurate, gives results in line with standard tests, and we will ensure it enhances NHS treatment pathways.

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