RAPID point-of-care infection detection and antibiotic-resistance TESTing enabled with laser-patterned microfluidic devices (RAPID-TEST)

点击翻译按钮获取中文摘要

The aim of this proposal is to use our proprietary laser printing technique to develop low-cost, paper-based diagnostic tests addressing a genuine unmet healthcare need, namely the rapid identification of bacterial infections and antibiotic susceptibility profiles to guide therapeutic decision making. Our point-of-care (POC) tests will be suitable for use in a clinic or by the patients themselves as part of a pre-consultation screening process or on-going home monitoring. We have already developed our paper testing platform and demonstrated excellent microfluidic properties, establishing the proof of principle that the devices can be impregnated with a colorimetric system capable of detecting the inflammatory marker, C-reactive protein. We are now building on this concept for developing excitingly ambitious and conceptually novel diagnostic tests for use at the POC. Our target diseases, urinary tract infections (UTIs) and the chronic airway disease in cystic fibrosis (CF) are in themselves serious and currently sub-optimally managed, but importantly, the successful technology will also be applicable to a large number of other medical and industrial applications. Bacterial infections affect large numbers of people, with significant quality of life and healthcare cost consequences. There have been very few new antibiotic agents developed over the last 1-2 decades and there is increasing concern over the global epidemic of antimicrobial resistance (AMR). A major part of this problem relates directly to the widespread and indiscriminate use of broad-spectrum, non-targeted antibiotics. Choosing the correct antibiotic is however difficult in the absence of an accurate diagnosis. Current protocols for the identification of an infecting pathogen and follow-on testing of its susceptibility to antibiotics are time-consuming and require specialist microbiology culture-based procedures. These approaches are not only costly and inconvenient, but there is a period of diagnostic uncertainty during which treatment is chosen empirically and may be sub-optimal. Patients' health and well-being is adversely impacted and these delays contribute to the emergence of AMR.Our proposed novel microfluidics-based devices will uniquely serve a dual purpose - first, rapid, POC identification of a pathogen and second, cheap and expedited testing for its antibiotic resistance profile. We will achieve this through the use of an optimised enzyme-linked immunosorbent assay (ELISA) to produce an immediate colour change on contact with the chosen bacterial antigen. We have selected three problematic bacteria causing UTIs and serious infection in patients with CF. Once single detection systems have been optimised, the next task will be to multiplex them onto the same device. Coupled with the detection system will be chromogenic, agar-based culture wells containing various antibiotics. After a short period of incubation, ~ 24 hours, colour changes will indicate the antibiotics to which the bacteria are resistant. This process would significantly reduce the current diagnostic time of 3-4 days.These tools will be important and timely for GPs/Consultants in delivering an accurate antibiotic treatment of their patient's infections with significant savings in healthcare costs. For the patients, there will be reduction in symptoms and consequent improvements in quality of life. In the context of CF, a life-long disease, the devices could be used by patients in their own homes for long-term surveillance, in a fashion very aligned with the UK CF Trust's flagship SmartCare programme; this will not only empower patients in self-management, and facilitate earlier treatment, but we may ultimately be able to allow non-infected patients to have contact with each other - lack of real-time knowledge of an individual's infection status currently mandates strict segregation which has a negative impact on patients' well-being.