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Sensitive and quantitative malaria diagnostic using nanoscale porous silicon.

使用纳米级多孔硅进行灵敏和定量的疟疾诊断。

基本信息

批准号：
10307596
负责人：
Sharon M Weiss
金额：
$ 18.89万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-11-24 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10307596
关键词：
Address Antibodies Antimalarials Area Azides Binding Biological Markers Biological Models Biosensing Techniques Biosensor Biotin Blood Blood Tests Blood specimen Cerebral Malaria Cessation of life Chemistry Child Communicable Diseases Data Detection Development Diagnosis Diagnostic Diagnostic tests Disease Drug resistance Ensure Film Fingers Goals Human Immobilization Individual Insecticide Resistance Label Malaria Malaria Diagnostic Materials Testing Measurement Measures Modeling Optics Parasites Pathway interactions Patients Performance Persons Play Polymers Property Proteins Protocols documentation Rapid diagnostics Reporting Research Resource Allocation Resources Risk Role Serum Signal Transduction Silicon Streptavidin Surface Symptoms System Testing Therapeutic Time Translations Work World Health Organization base burden of illness cost cost effective density detection limit detection sensitivity diagnostic tool high risk improved innovation malaria transmission meetings monomer nanoscale novel strategies point of care polymerization prevent protein biomarkers rapid detection sensor success

项目摘要

SUMMARY Recent malaria control efforts have yielded significant progress toward reducing the burden of this disease. A 25% reduction in malaria-related deaths was reported between 2010 – 2016. Despite this success, malaria still represents a staggering global burden with more than 200 million people infected in 2018, resulting in more than 400,000 deaths. Moreover, recent data collected by the World Health Organization suggest that no additional, significant progress has been made in reducing global malaria cases over the past few years. A key challenge to eradicating malaria is diagnosing asymptomatic malaria patients who are unlikely to receive anti-malaria drugs despite being able to cause transmission of the malaria parasite to others. At the same time, quantification of malaria parasites in people expressing malaria symptoms is also of critical importance to finding patients who are at high risk for cerebral malaria, which is often fatal, especially in children. Hence, compounded by increasing insecticide and drug resistance, there is a critical need to develop new approaches for widely deployable malaria rapid diagnostic tests (RDTs) that are accurate over a large dynamic range, identifying both asymptomatic patients and those at risk for cerebral malaria. Current RDTs cannot meet this need. This proposal seeks to achieve important milestones towards the development of a porous silicon optical diagnostic for malaria that can meet the aforementioned critical need in an easy-to-use and affordable platform. We will first demonstrate highly sensitive and quantitative malaria biomarker (PfHRP2) detection using optical readout of porous silicon films in a model system (Aim 1) and then demonstrate robust detection of the malaria biomarker in blood (Aim 2). This work leverages the simplicity in measuring changes in the optical properties of porous silicon that directly correlate to the quantity of protein captured in the pores, and the large internal surface area of porous silicon within a small areal footprint that enables the efficient capture of significantly more malaria biomarkers per finger-prick of blood than current RDTs. Key scientific innovations include grafting a bifunctional polymeric brush from porous silicon to realize both a high density of capture probes for malaria biomarkers and antifouling properties to ensure negligible non-specific binding when testing blood samples. We have assembled a research team with expertise in optics and nanoscale porous biosensors (Weiss), surface chemistry and antifouling coatings (Laibinis), and low resource diagnostic tools for infectious diseases (Adams) to address the need for improved RDTs for malaria control and elimination. We expect our porous silicon optical diagnostic to enable more informed treatment of malaria patients across a wide spectrum. Expected long-term impacts include improved global surveillance for malaria resource allocation and elimination of malaria.

总结最近的疟疾控制工作在减轻这种疾病的负担方面取得了重大进展。一据报告，2010 - 2016年间疟疾相关死亡减少了25%。尽管取得了这一成功，这是一个惊人的全球负担，2018年有2亿多人感染，四十万人死亡。此外，世界卫生组织最近收集的数据表明，过去几年，在减少全球疟疾病例方面取得了重大进展。一个关键挑战根除疟疾的关键是诊断那些不太可能接受抗疟疾药物治疗的无症状疟疾患者，尽管它能够将疟原虫传播给其他人。同时，量化表现疟疾症状的人体内的疟疾寄生虫对于发现患脑型疟疾的风险很高，这种疟疾往往是致命的，特别是在儿童中。因此，通过增加由于杀虫剂和药物抗药性，迫切需要开发新的方法来对付可广泛部署的疟疾快速诊断测试（RDT）在大动态范围内准确，患者和有患脑型疟疾风险的患者。目前的RDT无法满足这一需求。该提案旨在实现多孔硅光学器件发展的重要里程碑疟疾诊断，可以满足上述关键需求，在一个易于使用和负担得起的平台。我们将首先展示使用光学显微镜的高灵敏度和定量疟疾生物标志物（PfHRP 2）检测。在模型系统中读出多孔硅薄膜（目标1），然后证明疟疾的稳健检测血液中的生物标志物（目的2）。这项工作利用了测量光学性质变化的简单性，多孔硅，其与孔中捕获的蛋白质的量直接相关，以及大的内表面在一个小的面积足迹内的多孔硅区域，能够有效地捕获更多的疟疾比目前的RDT更高的生物标志物。关键的科学创新包括嫁接一个双功能的从多孔硅聚合刷，以实现疟疾生物标志物的高密度捕获探针，可确保在测试血液样本时可忽略非特异性结合的特性。我们已经组建了一个研究团队，具有光学和纳米多孔生物传感器（韦斯），表面化学和生物涂层（莱比尼斯），传染病的低资源诊断工具（亚当斯）满足改进RDT以控制和消除疟疾的需要。我们希望我们的多孔硅光学诊断，使更知情的治疗疟疾患者在广泛的范围。预期长期所产生的影响包括改善了对疟疾资源分配和消灭疟疾的全球监测。