A Novel, Real-Time Tuberculosis Detector for Animals and Humans

Mycobacterium tuberculosis (TB) is a major cause of suffering and death in humans and animals worldwide, the second leading infectious killer of humans after COVID-19. There are currently around 10 million recorded human TB infections per year, with a death rate of 1.8 million per year. TB imposes major economic losses and trade barriers world-wide, impacting disproportionately on the livelihoods of poor and marginalized communities. Zoonotic TB poses special challenges for patient treatment and recovery since the advanced laboratory tools required for its diagnosis are frequently unavailable, so patients are often misdiagnosed and may receive ineffective treatment. This is a particular problem in resource-poor countries, where diagnostic tools capable of accurate and rapid diagnosis at the time of initial patient consultation are not available. There is also two-way transmission between cattle and wild animals (e.g. badgers in the UK). The high prevalence of the disease in parts of the UK, coupled with the test and slaughter strategy for disease control, has a major effect on both the livelihoods and wellbeing of farmers. The surveillance, diagnostic testing, badger culling and vaccination costs the UK government alone a total of £100 million per year. Ending the human TB epidemic by 2050 is a UN sustainable development goal and the WHO recommends the development of more effective rapid diagnostic tests to improve patient outcomes. Hence our vision is the development of a novel, point-of-care TB detector for humans and animals capable of delivering a result within 1 hour. It will improve on state-of-the-art approaches in terms of specificity, sensitivity and time to result (compared to hours for PCR, days for microscopy). Our multi-disciplinary objectives, drawing on our team's individual expertise, will focus on each of the detector's modular components. We will develop a novel and hygienic sample cartridge to accept real-word samples of up to 10 ml volume, incorporating all of key elements of sample preparation, DNA concentration and signal generation. We will use pulsed, highly targeted 2.45 GHz microwaves for the instantaneous liberation of the target, bacterial DNA. We will separate and concentrate the target DNA using magnetic separation using functionalised magnetic nanoparticles, for its presentation to a functionalised metal surface for photonic detection. These elements will draw on our expertise in design of suitable DNA probes. Signal generation will be based on a novel, optical resonance based refractive index sensor, to provide real-time results with no fluorescent labelling. Our technology will be completely transformative in the rapid diagnosis of TB and will be simple enough to be operated by any healthcare worker or farmer. With further translational funding beyond the current project it can be reduced in both size and cost to allow a simple, low-cost detector, which will have particular benefit for use in developing countries. Our platform can be easily adapted to detect most other pathogens, including SARS-CoV-2, MRSA, etc., so it could become an important tool to help control the spread of future pandemics. Our project fits with the scheme's objectives in that it is truly interdisciplinary, bringing together experts in veterinary medicine, microbiology, microwave and photonic engineering, to develop a novel, disruptive solution to a world-wide healthcare problem. We will adopt new approaches and generate new understanding that would not otherwise emerge from our single disciplines, delivering the required reciprocal benefits defined by the funding scheme.