Integrated ultrasonic biosensing for point-of-care diagnostics

背景近2.6亿人感染了血吸虫病，其中90%的感染发生在撒哈拉以南非洲。有必要开发新的高度敏感的诊断方法，使其能够监测治疗结果，具体目标是(I)防止局部治疗后再次出现感染；以及(Ii)通过确保有效和适当的治疗来减少耐药性。目的：我们将开发一种新的低成本、快速(&lt；30分钟)、护理点、高灵敏的粪便检测方法，该方法使用基于等温扩增的纸质(低成本)DNA分析(例如LAMP)来检测曼氏葡萄球菌(虫卵)和血吸虫杂交种的能力。该设备将分离鸡蛋，裂解样本，并检测物种特有的DNA。我们的目标是在乌干达的患者样本上获得该设备现场性能的初步概念验证数据。据我们所知，这将是这些基于粪便样本的低成本方法的第一次，并在一系列其他蠕虫感染中具有潜在的应用前景。血吸虫生活在肝门静脉，并将细胞输送到血液中。因此，在粪便检测的同时，我们还将开发一种基于血液的检测方法，通过指检血液来检测DNA。该检测将再次配置为低成本的纸质检测，并将发展为双重检测，使疟疾和血吸虫病(血吸虫病)能够同时检测到。这将指导发烧患者的适当治疗通过实现低成本、护理点基因组诊断，该项目专门与EPSRC的医疗技术主题保持一致，包括通过监测疗效来优化治疗，发展工程和传感器等优先研究领域的能力。这项研究是基于由EPSRC资助的SAW Made in EPSRC活动(库珀奖学金，ProxEconomics项目)的基本发展。好处：该项目与全球挑战基金的健康优先事项保持一致，该基金的目标是“解决疾病、加强卫生系统并惠及世界上最脆弱的人群”。根据世卫组织的最新估计，2014年至少有2.58亿人需要治疗血吸虫病，据报道有6160万人接受治疗。需要治疗的人中有90%生活在非洲。在儿童中，血吸虫病会导致贫血、生长发育迟缓和学习能力下降。治疗通常会逆转这些效果，但需要监测其疗效，以确定治愈和适应疗法。如果不治疗，慢性病会影响人们的工作能力，并可能导致死亡。据估计，疾病负担占450万DALY(残疾影响寿命年)。十多年来，乌干达通过国家管制方案进行了大规模的吡喹酮药物管理。发现了感染热点，那里的流行率、强度和相关发病率现在高于基线水平。通过过度使用或适当使用而出现的吡喹酮耐药性被视为一大威胁。与当地社区一起进行现场诊断是确保在治疗结束之前进行适当的药物管理而不过度暴露的关键。合作者。Edridah Muheki Tukahebwe博士，乌干达卫生部；研究记录：Poppy Lamberton(MVLS)博士将帮助进行实地研究，并与Tukahebwe博士长期合作。

Context Nearly 260 million people are infected with schistosomiasis with >90% of infections found in sub-Saharan Africa. There is a need to develop new highly sensitive diagnostic methods that enable to monitor treatment outcomes, with the specific aims of (i) preventing re-emergence of infections following local treatment; and (ii) reducing resistance by ensuring effective and appropriate treatment.Aims: We will develop a new low-cost, rapid (<30 min), point-of-care, highly sensitive stool-based test which the ability to detect S. mansoni (eggs), and Schistosoma hybrids using a paper based (low cost) DNA assay based upon isothermal amplification (e.g. LAMP). The device will separate the eggs, lyse the sample and detect species specific DNA. We aim to obtain initial proof-of-concept data of the performance of the device in the field in Uganda on patients' samples. To our knowledge, this will be the first instance of these low cost methods for looking at stool based samples and has the future potential applications in a range of other helminth infections.The schistosoma live in the hepatic portal vein and shed cells into the blood. In parallel with the stool test, we will therefore also develop a blood based assay, where DNA will be detected from a fingerpick of blood. The assay will again be configured as a low cost, paper based assay and will be developed as a duplex, enabling both malaria and bliharzia (schistosomiasis) to be detected at the same time. This will guide appropriate treatment for febrile patientsThrough enabling low-cost, point-of-care genomic diagnostics, the project aligns specifically with EPSRC's Healthcare Technology theme, including optimising treatment by monitoring efficacy, developing capabilities in priority research areas such as Engineering and Sensors. This research is based on fundamental developments in SAW made in EPSRC-funded activity (Cooper fellowship, Proxomics project). Benefits: This project is aligned with the Health priority of the Global Challenge Fund, which aims 'to tackle diseases, strengthen health systems and reach the worlds' most vulnerable'. Inded, according to the latest WHO estimates, at least 258 million people have required treatment for Schistosomiasis in 2014, with 61.6 million people reported to be treated. 90% of those requiring treatment live in Africa. In children, Schistosomiasis causes anaemia, stunted growth and reduced ability to learn. Treatment usually reverses these effects, but its efficacy need to be monitored to establish cure and adapt therapy. If untreated, chronic disease affects people's ability to work and can result in death. The disease burden has been estimated to account for 4.5 million DALYs (disability affected life years).Mass drug administration of praziquantel has been delivered through National Control Programmes in Uganda for over a decade. Hotspots of infection have been detected, where prevalence, intensity and associated morbidity are now higher than they were at baseline. Emergence of praziquantel resistance through over-use or in appropriate use is seen as a major threat. Field based diagnosis, with local communities, is key to ensure that appropriate administration of the drug is carried out until treatment is complete, without over exposure. Collaborators. Dr. Edridah Muheki Tukahebwe, Ministry of Health, Uganda; Track record in research: Dr Poppy Lamberton (MVLS) will help with field studies and has a long established collaboration with Dr Tukahebwe.