PRADA (Portable Rapid Automated DNA Analysis)

影响人类的细菌感染的增加没有减弱的迹象，性传播疾病、性病和耐抗生素超级细菌在我们医院的爆发病例不断增加。为了对付这些威胁，减轻卫生服务日益加重的负担，必须迅速诊断出感染的病原体。早期诊断将使患者能够更及时地接受治疗，从而减少痛苦，增加成功的机会。更重要的是，它将最大限度地减少交叉污染，避免严重疫情爆发的灾难性后果。因此，PRADA的目标是通过开发可在医院、全科医生手术和其他护理点环境中“在床边”使用的技术，尽早快速检测导致关键传染病的病原体，例如，养老院这将通过设计和开发一种便携式设备来实现，该设备可用于通过检测特定传染性生物体的部分染色体/DNA生物标志物来简单快速地诊断其存在。通过将该仪器定位在护理点环境中，它将消除将样本发送到遥远的专业参考实验室的需要。因此，在几分钟内而不是几天内就可以作出诊断。治疗可以立即开始，在医院，感染控制小组可以在尽可能早的时刻得到关于严重传染因子存在的警报。该项目将侧重于开发针对性传播感染、肠道疾病以及由MRSA和艰难梭菌引起的医院获得性感染的优先检测方法。然而，该仪器将能够进行许多其他传染病测试（人类和动物，病毒和细菌）以及基因测试。该系统将采用由领导该项目的商业合作伙伴Enigma Diagnostics开创的技术。这项技术已经在实验室和现场得到了验证。国防部、兽医实验室机构和动物卫生研究所已经试用了一种更大的第一代仪器（Enigma FL）。仪器开发将由Enigma Diagnostics使用内部工程资源领导，并将专业活动分包给工程顾问Sagentia进行设计，原理验证和制造。它将分为两个相互关联的工作方案，涵盖消耗性弹药筒、硬件和软件。在开发过程中的多个阶段，将咨询最终用户，以确保系统规格符合性能、易用性、可靠性和成本要求。分析测试将由诺丁汉大学和诺丁汉特伦特大学的专业研究中心设计。他们将利用对MRSA、艰难梭菌、弯曲杆菌和沙门氏菌的临床重要菌株的现有知识，设计专门的标记DNA集，从而允许使用最终的PRADA机器检测临床标本中的每一类细菌。这些将在计算机分析每种细菌的完整基因组（遗传蓝图）的基础上设计，并通过实验方法进行。选定的DNA生物标志物将进行严格的测试，以确保它们能够检测到特定细菌的所有例子，并且它们不会错误地牵连其他细菌。在确定了生物标志物的特异性和选择性之后，它们将被纳入适合Enigma技术的测定格式中，并在新的便携式仪器中对其有效性进行严格测试。

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.