Public Funding for Fuse Diagnostics Limited

Chlamydia (CT) and Gonorrhoea (NG) are the two most prevalent sexually transmitted infections, with 129m and 82m cases worldwide in 2020, respectively. Most CT/NG infections are asymptomatic yet if left untreated can cause pelvic inflammatory disease, leading to infertility and ectopic pregnancy. The infection rate in developed countries has increased persistently over the last 15 years, despite the implementation of national screening programmes. The emergence of multi-drug resistant NG is of increasing concern on a global basis. CT/NG is currently diagnosed using nucleic acid amplification tests using complex instruments which require a central testing location. This approach reduces flexibility, adds cost and leads to poor uptake and delayed treatment. Improved diagnostic tests for CT/NG are important to identify more individuals requiring treatment and ensure timely and appropriate use of antibiotic treatments. In this project we are developing an instrument-free molecular test for CT/NG, which brings the accuracy of a laboratory-based nucleic acid amplification test into a simple, flexible, disposable format analogous to an antigen test. This new class of test would greatly facilitate decentralised testing for CT/NG by untrained users in any setting and thus help to combat the CT/NG epidemic and mitigate the threat of antimicrobial resistant bacteria.

In this project we are developing a next-generation instrument-free molecular diagnostic test for seasonal respiratory viruses (Flu, COVID-19 and RSV) with potential to transform management of the next pandemic. The COVID-19 pandemic highlighted the fundamental flaws with conventional diagnostic tests for respiratory viruses. Whilst laboratory PCR (molecular) tests exhibit gold-standard performance they require specialist equipment and complex logistics meaning that results are not available in time to inform effective treatment or isolation decisions. In contrast, rapid lateral flow tests are cheap and convenient but miss many cases of infection due to their inherant low sensitivity and variable performance. With COVID-19 becoming endemic and a resurgence in Flu and RSV, there remains a critical need for improved diagnosis and treatment of respiratory infections to minimise outbreaks and protect vulnerable groups and the healthcare system. Instrument-free molecular diagnostic tests promise to address this challenge by combining the compelling clinical benefits of laboratory PCR with the flexibility of a disposable device for decentralised use. Whilst the technical feasibility of molecular testing in a disposable device has been demonstrated, first-generation tests do not meet wider market expectations, due to their inherent cost, environmental footprint and slow time-to-result. Our test combines a transformative simplification in device design with enhanced molecular technology, to realise a fundamental reducion in cost-of-goods and environmental impact. The test will deliver laboratory PCR accuracy in an ultra-rapid (<10 min) versatile multiplex format, ideally suited to widespread deployment in any use setting. The benefits of the test include improved treatment of patients, fewer hospitalisations, better use of antibiotics, fewer deaths and significantly lower overall healthcare costs. Future use at hospitals, GPs and nursing homes will enable more effective prevention and infection control and support pandemic preparedness.

This project is focussed on engineering enzymes to realise a highly innovative instrument-free molecular diagnostic testing platform. The COVID-19 pandemic highlighted the flaws with conventional approaches to the detection of respiratory viruses. Whilst laboratory PCR (molecular) tests exhibit gold-standard performance they require specialist equipment and complex logistics meaning that results are not available in time to inform effective treatment or isolation decisions. In contrast, rapid lateral flow tests are cheap and convenient but miss many cases of infection due to their inherent low sensitivity and variable performance. Enzymes are at the heart of every molecular diagnostic test, yet historically little effort has been made to tailor their properties for innovative product formats. Recent advances in engineering biology now present a compelling opportunity to design and engineer enzymes with the required performance to realise fundamentally new classes of test. The enhanced enzymes engineered in this project will enable an instrument-free molecular test that achieves laboratory PCR accuracy in a simple, rapid, low-cost device analogous to an antigen test, combining the benefits of each type of test.