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.

项目概要 尽管快速诊断测试（RDT）旨在促进家庭测试，但通常在医院中使用 基于护理点 (POC) 的设置，用于诊断寄生虫密度较高（>2000 每微升血液），部分原因是当前基于侧流的方法缺乏敏感性和稳定性。 在当前的项目中，我们建议开发一种新型的按需纸质诊断平台。 这将实现自测试（或现场分析），然后使用便携式设备进行远程和集中信号检测 这种诊断方法是创新的，因为它结合了新的简单性和水平。 实用性、适度的成本水平和集中式检测策略，这将重新定义检测的广度 准确的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。 将提供在疾病出现临床症状之前诊断无症状患者的机会， 因此，我们将提供负担得起的基于社区的监测和 POC 测试。 通过合理设计新型离子探针与特定抗体偶联，随后将 实现利用垂直流体流动格式的纸基免疫测定平台。 通过酶，这些稳定的离子探针能够中断、存储和恢复 免疫分析测试，允许在以后方便的时间进行检测此外，离子探针是合理的。 设计用于在刺激时产生小质量离子，允许在现场使用便携式仪器 通过针对所有三个级别的疟疾护理（即有症状的 POC 患者、基于监测的患者）进行分析。 疫情爆发时的无症状检测和现场分析），我们将提供更大的机会限制 1.88 亿疟疾病例并减少每年 120 亿美元的工人生产力损失。 设计和合成活性（可裂解）离子探针作为我们提出的质谱分析的批量生产者 还提出了两种基于 MS 的免疫分析技术。 对手指刺血中的低寄生虫密度进行超灵敏检测 Aim 2 将开发和优化 基于纸的 MS 免疫分析平台通过执行两个相互关联的任务：建立离子探针 普通纸质介质介导的免疫测定，以及新的片上MS检测方法的开发 为了促进纸质设备的易用性，目标 3 涉及通过密切验证该方法。 与两位分子生物学家的合作互动（Kingsley Badu – 与 PI 无关；KNUST，加纳，以及 Cristian Koepfli 博士 - 加州大学欧文分校公共卫生学院 James Odei 博士（俄亥俄州临床生物统计学）。 州立大学）是为了进行适当的数据分析和解释，作为此目标的一部分，我们计划进行筛选。 使用所开发的论文对至少 1,600 名恶性疟原虫 (P) 患者/志愿者（加纳）进行了研究 设备；我们预计包括约 50% 15 岁以下的儿童。该方法还将针对间日疟原虫进行验证。 从埃塞俄比亚采集的疟疾样本（预计约 600 名志愿者）。