PRADA (Portable Rapid Automated DNA Analysis)

Lead Research Organisation: University of Nottingham
Department Name: Sch of Molecular Medical Sciences


The rise in bacterial infections affecting mankind shows no sign of abating, with ever increasing cases of sexually transmitted disease, diarrheal illnesses and outbreaks of antibiotic resistant superbugs in our hospitals. To counter the threats posed, and to relieve the escalating burden being placed on health services, it is imperative that the causative agent of infection is rapidly diagnosed. Early diagnosis will allow patients to receive treatment in a more timely manner, thereby reducing suffering and increasing the chances of a successful outcome. More importantly, it will minimise cross contamination and avert the catastrophic consequences of a serious outbreak. The objective of PRADA is, therefore, to enable the rapid detection of the agents responsible for key infectious diseases at the earliest possible moment by developing technology that can be used 'at the bedside' in hospitals, GP surgeries and other point-of-care settings, eg., nursing homes. This will be achieved through the design and development of a portable piece of equipment that can be used to simply and rapidly diagnose the presence of specific infectious organisms through the detection of part of their chromosome / a DNA biomarker. By locating this instrument in a point-of-care-setting, it will remove the need to send samples to a distantly located specialised reference lab. Definitive diagnosis will, therefore, be possible within minutes rather than days. Treatment can begin immediately, and, in hospitals, infection control teams can be alerted to the presence of serious infectious agent at the earliest possible juncture. The project will focus on the development of priority assays for sexually transmitted infections, diarrhoeal diseases and the hospital-acquired infections caused by MRSA and Clostridium difficile. However, the instrument will be capable of performing many other infectious disease tests (human and animal, viruses and bacteria) as well as genetic tests.The system will incorporate technologies that have been pioneered by the commercial partner leading this project, Enigma Diagnostics. This technology has already been proven in the laboratory and the field. A larger, first generation instrument (Enigma FL) has already been trialled with the Ministry of Defence, the Veterinary Laboratory Agencies and the Institute of Animal Health. The instrument development will be led by Enigma Diagnostics using in-house engineering resources, as well as sub-contracting specialist activities to engineering consultants Sagentia for design, proof-of-principle and fabrication. It will be divided into two intricately connected work programmes covering the consumable cartridge, hardware and software. At multiple points through the development, end-users will be consulted to ensure that the system specifications will meet the requirements for performance, ease-of-use, reliability and cost.The assay tests will be designed by specialist research centres at University of Nottingham and Nottingham Trent University. They will use existing knowledge of the clinically important strains of MRSA, Clostridium difficile, Campylobacter, and Salmonella to design the specialised marker DNA sets which will allow the detection of each class of bacteria in clinical specimens using the final PRADA machine. These will be designed on the basis of computer analysis of the complete genomes (genetic blueprints) of each type of bacteria, as well as through experimental approaches. Selected DNA biomarkers will be rigorously tested to ensure that they are capable of detecting all examples of a particular bacterium, and that they do not wrongly incriminate other bacteria. Having established the specificity and selectivity of the biomarkers, they will be incorporated into an assay format appropriate to the Enigma technology and their effectiveness in the new, portable instrument rigorously tested.


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Description The project was original established to derive new rapid assays for the diagnosis of Staphylococcus aureus and Clostridium difficile using Enigma's proprietary rapid DNA amplification technology, the Enigma ML. It provides fully integrated and automated raw sample to result, real-time PCR diagnostic testing for laboratories, local hospitals, at point-of-care locations.. However, at an early stage of the project the scope of the project was reduced at Enigma's behest to just C. difficile.

Quantitative laboratory-based assays were developed, and procedures devised that allowed their implementation on clinical, faecal samples. The transference to a commercial assay was not completed by the projects end.

Our involvement benefited the University by the establishment of a working relationship with a commercial company in the arena of molecular diagnostics (Enigma), as well as strengthening collaboration with Nottingham Trent University. It provided the staff involved with a better appreciation of what is required for the commercial exploitation of academic research into diagnostic tests directed against infectious diseases, and provided a route for future developments going forward. Whilst we did not achieve all that we would have wished from a scientific standpoint, due to a multitude of unforeseen factors, at the end of the project the way forward was clear, and great opportunities existed for the commercialisation of our C.difficile test through further interactions with Enigma via other mechanisms, eg., a KTP award. The company chose not to follow up on these opportunities.
Exploitation Route Preliminary data on the C. difficile assay was presented as a poster at the 3rd International Meeting on Clostridium difficile, Bled, Slovenia, Sept 2010. Our involvement was on the whole beneficial, and has increased the chances of our research leading to a commercial product. It is apparent now that the greatest success will come from projects where the goals and methods of achieving them are clearly set out from the outset and adhered to.
Sectors Healthcare

Description Whilst the prototype C. difficile assay developed could have potentially been translated into a commercial product, it was not taken forward by Enigma.
First Year Of Impact 2010
Sector Healthcare