New, easy to use, low-cost technologies based on DNA origami biosensing to achieve distributed screening for AMR and improved antibiotic prescribing

Biosensing technologies have great potential to help realise an age where healthcare can be delivered more efficiently due to an accelerated, simplified and less expensive diagnostic pathway. Antimicrobial resistance (AMR) is one of the most significant societal challenges we face and because of its nature requires a coordinated global response. Without action, by 2050, AMR could lead to 10 million deaths globally each year making it more dangerous that cancer and heart disease combined. AMR is a multifaceted problem with many paths to improving the situation. Two key aspects are diagnosis and targeted prescribing of drugs. This project will assist with these two challenges by developing cutting-edge diagnostic technologies which are highly sensitive, highly accurate but crucially low cost and highly manufacturable because the designed sensors will rely on the use of simple, easy to source and highly manufacturable components such as synthetic DNA, low-cost test strips and quartz-based materials. By exploiting developments in an emerging area of nanotechnology (DNA origami) the project will utilise precisely designed DNA shapes and structures attached to sensor surfaces to sense for the presence of bacteria and key drug resistance genes first in simulated and finally in clinical samples with high analytical sensitivity and high precision. The findings of the project will be used to develop the next generation of medical devices which will operate by the high sensitivity and high accuracy sensing mechanisms developed in this project.

Detecting whole pathogens and antibiotic resistance genes is crucial to diagnose, monitor and treat drug-resistant infections. Electrochemical approaches are attractive because they lend themselves to high volume manufacture, low cost, multiplex measurements, high analytical sensitivity, low complexity instrumentation and connectedness. DNA origami is an extremely promising material for functionalisation of electrode surfaces as it allows precise spatial and functional control when designing and immobilising nanostructured materials, can provide signal amplification, is compatible with well-established surface modification chemistries and highly scalable. In addition, DNA origami has advantages which overcome drawbacks with traditional SAM-based sensors which are known to suffer from poor reproducibility and inability to be sufficiently stabilised for long term storage. The consortium has demonstrated the potential of DNA origami, AC impedance-based techniques and quartz nanopores for enhanced biosensing, with a view to developing next-generation low-cost diagnostic technologies. In this project, new DNA origami structures designed to detect biological markers of high relevance to AMR (whole pathogens & nucleic acid sequences) will be developed and exemplified via impedance and nanopore sensing, giving significant progress in AMR diagnosis and monitoring. This innovative research programme will be complemented with an effort on translation and IP exploitation to ensure the project reaches maximum impact by setting the developed technologies on a pathway to adoption.