Novel System to Accelerate Development of New Diagnostic Tests

Unlike polymerase chain reaction, or PCR, tests, which require access to sophisticated labs operated by trained staff, isothermal tests like loop-mediated DNA amplification (LAMP) can offer quick, accurate results by creating interactions between chemicals and the DNA strands contained in patient samples and delivering rapid results at the point of care. However, in many cases, those rapid tests are designed and developed for a specific purpose, which can introduce unnecessary complexity and make it difficult for one test to be easily adapted for use in a different diagnosis. Researchers have now developed a more generalizable approach to the creation of new tests, building a software tool capable of turning the reaction graphs into suggestions as to how chemical primers and reactions could be used to create the desired diagnostic results. The software which helps speed up the process of creating new diagnostic tests could help combat future pandemics, its developers say.

The system, developed by a team of bioengineers and chemists from the University of Glasgow (Scotland, UK) and Shanghai Jiao Tong University (Shanghai, China), suggests new reaction pathways to accelerate the design and development of new diagnostic assays. It is freely available for other researchers around the world to investigate, adapt and use, can also be used to identify the early stages of non-infectious diseases like cancer, which could help patients receive more timely treatment. The researchers first began by developing reaction graphs – representations of the biomechanical processes which enable rapid diagnostic tests like cross priming amplification (CPA) and LAMP.

They probed the effectiveness of the software by using it to design the chemical primers and reactions for four different diagnostic tests – three for infectious diseases and one for cancer, a non-communicable disease. The researchers successfully created a multiplexed test for a form of HIV with high levels of sequence variations, a highly sensitive test for tuberculosis, and a study for analyzing patient clinical samples for the presence of hepatitis B. The team also developed an assay to detect short miRNA sequences relevant in the diagnosis and prognosis of cancers, including oral squamous cell carcinoma, breast cancer and glioma. They used their newly-designed diagnostic assays to test patient-derived samples from clinical laboratories in China. Then, the researchers confirmed their results using separate PCR tests. They tested their results against LAMP diagnostics for the same diseases, finding that their results were more specific and reproducible than the LAMP tests.

“Our programmable system automates a lot of the early trial-and-error work that goes into the development of new tests, and we’ve shown that it can be used to reliably diagnose a useful cross-section of communicable and non-communicable diseases. It’s an exciting discovery, and suggests many potential applications in medicine,” said Professor Jon Cooper, of the University of Glasgow’s James Watt School of Engineering, who is the paper’s lead author.

“Our programmable system offers one new route to supporting that kind of fast diagnostic development,” added Dr Julien Reboud, a co-author of the paper from the University of Glasgow. “We’re keen to make it as accessible as possible to other researchers around the world, so we’ve made all our graphs and data freely available online. We hope that it will be of real use to researchers and clinicians across a wide range of applications, and we look forward to seeing the new applications they will find for the system.”

Related Links:
University of Glasgow 
Shanghai Jiao Tong University