Malaria Management through an On-demand Diagnostic Approach using Novel Ionic Probes

使用新型离子探针通过按需诊断方法进行疟疾管理

• 批准号: 9926216
• 负责人: Abraham Badu-Tawiah
• 金额: $ 20.05万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926216
• 关键词: 3-Dimensional; Africa; Age; Aldehyde-Lyases; Antibodies; Antigens; Asia; Bedside Testings; Biological Markers; Biometry; Blood; Blood specimen; California; Caring; Characteristics; Chemical Structure; Child; Clinical; Communities; Country; Coupling; Data Analyses; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Outbreaks; Drops; Enzymes; Ethiopia; Evaluation Studies; Film; Fingers; Generations; Ghana; Home environment; Hospitals; Immunoassay; Infection; International; Interruption; Investigation; Ions; Lateral; Link; Malaria; Mass Screening; Mass Spectrum Analysis; Mediating; Methods; Microfluidics; Microscopy; Molecular; Ohio; Paper; Parasites; Patient Care; Patients; Performance; Plasmodium; Plasmodium falciparum; Prevalence; Productivity; Public Health; Reaction; Reaction Time; Reagent; Reporter; Research; Risk; Sampling; Sensitivity and Specificity; Signal Transduction; South America; Surface; Techniques; Technology; Testing; Time; Universities; Validation; Vivax Malaria; Waxes; base; catalyst; cost; density; design; fluid flow; histidine-rich proteins; infection burden; innovation; instrument; malaria infection; mass spectrometer; meetings; nanoGold; novel; point of care; portability; protein biomarkers; regenerative; screening; surveillance study; tool; transmission process; volunteer; waiver

Project Summary Although designed to facilitate home testing, rapid diagnostic test (RDT) have typically been used in a hospital- based point-of-care (POC) setting for diagnosis of symptomatic patients where parasite density is high (>2000 per microliter of blood). This is, in part, due to the lack of sensitivity and stability of current lateral flow-based RDT devices. In the current project, we propose to develop a novel on-demand paper-based diagnostic platform that will enable self-testing (or field analysis) followed by remote and centralized signal detection using portable mass spectrometers. This diagnostic approach is innovative as it combines new levels of simplicity and practicality, modest levels of cost, and a centralized detection strategy, which will redefine the breadth of application and performance/cost ratio for accurate malaria detection. More importantly, our proposed approach will provide an opportunity to diagnose asymptomatic patients before the disease becomes clinically apparent, therefore providing affordable community-based surveillance and POC tests. We will achieve this objective through the rational design of novel ionic probes for coupling to specific antibodies, which will subsequently enable the implementation of a paper-based immunoassay platform utilizing vertical fluid flow format. Compared with enzymes, these stable ionic probes make possible the ability to interrupt, store, and restore the immunoassay test, allowing detection at a later convenient time. In addition, the ionic probes are rationally designed to yield ions of small masses upon stimulation permitting the use of portable instruments for field analysis. By targeting all three levels of malaria care (i.e., symptomatic POC patients, surveillance-based asymptomatic detection and field analysis in an outbreak), we will offer a greater chance of limiting the 188 million cases of malaria and reduce the $12 billion yearly loss in worker productivity. Aim 1 is to design and synthesize active (cleavable) ionic probes as mass reporters for our proposed mass spectrometry (MS)-based immunoassay technology. Two signal amplification strategies are also proposed to enable ultrasensitive detection of low parasite density from a finger prick blood. Aim 2 will develop and optimize the paper-based MS immunoassay platform by implementing two interrelated tasks: establishment of ionic probe- mediated immunoassay on ordinary paper substrate, and the development of new on-chip MS detection methods to facilitate the ease of use of the paper devices. Aim 3 involves validation of the method, through close collaborative interactions with two molecular biologists (Kingsley Badu – not related to PI; KNUST, Ghana, and Dr. Cristian Koepfli - University of California, Irvine, Public Health). Dr. James Odei (Clinical Biostatistics, Ohio State University) is included for proper data analysis and interpretation. As part of this aim, we project screening of at least 1,600 patients/volunteers with Plasmodium (P) falciparum (in Ghana) using the developed paper device; we expect to include ~50% children under age 15. The method will also be validated against P. vivax malaria samples (~600 volunteers expected) collected from Ethiopia.

项目摘要 尽管设计用于促进家庭测试，但通常在医院中使用快速诊断测试（RDT） - 基于寄生虫密度较高的有症状患者的基于护理点（POC）设置（> 2000 每微晶的血液）。这部分是由于电流基于横向流的敏感性和稳定性 RDT设备。在当前的项目中，我们建议开发一个新颖的基于纸的诊断平台 这将实现自我测试（或现场分析），然后使用便携式远程和集中的信号检测 质谱仪。这种诊断方法具有创新性，因为它结合了新的简单水平和 实用性，适中的成本水平和集中检测策略，这将重新定义 用于准确疟疾检测的应用和性能/成本比。更重要的是，我们提出的方法 将在疾病变得明显之前提供一个诊断不对称患者的机会， 因此提供负担得起的基于社区的监视和POC测试。我们将实现这一目标 通过与特定抗体耦合的新离子问题的合理设计，随后将 启用利用垂直流体流格式的纸质免疫测定平台实现。比较的 使用酶，这些稳定的离子问题使中断，存储和恢复的能力有可能 免疫测定测试，允许在以后的方便时间内进行检测。另外，离子问题是合理的 设计以在刺激时产生小物质，允许使用便携式仪器进行现场 分析。通过靶向所有三种水平的疟疾护理（即有症状的POC患者，基于监视的患者 爆发中无症状的检测和现场分析），我们将提供更大的机会限制 1.88亿例疟疾病例，减少了工人产量的每年120亿美元的损失。目标1是 设计和合成主动（可裂解）离子探针作为我们提出的质谱法的质量记者 （MS）基于免疫测定技术。还提出了两种信号放大策略以实现 从手指刺血血液中对低寄生虫密度的超敏感检测。 AIM 2将开发并优化 基于纸张的MS免疫测定平台通过实施两个相互关联的任务：建立离子探针 - 普通纸基板上的介导的免疫测定，以及新的片上MS检测方法的开发 为了方便易用纸张设备。 AIM 3涉及该方法的验证，通过关闭 与两位分子生物学家（金斯利·巴杜（Kingsley Badu） - 与pi无关； knust，加纳和 Cristian Koepfli博士 - 加利福尼亚大学，尔湾分校，公共卫生）。詹姆斯·奥迪（James Odei）博士（俄亥俄州临床生物统计学 包括州立大学）用于适当的数据分析和解释。作为此目标的一部分，我们预测筛查 使用已发表的纸 设备;我们预计将包括约50％的15岁以下儿童。该方法还将针对Vivax进行验证 从埃塞俄比亚收集的疟疾样品（预计约600名志愿者）。