Rapid diagnosis and quantification of HIV by direct capture, labelling and detection of individual virions

通过直接捕获、标记和检测单个病毒颗粒来快速诊断和定量 HIV

• 批准号: 9977120
• 负责人: Ashutosh Chilkoti
• 金额: $ 44.43万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977120
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Antibodies; Awareness; Binding; Binding Sites; Biological Assay; Blood; Cellular Phone; Cessation of life; Chronic; Clinical; Clinical Trials; Country; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Diffusion; Disease; Disease Management; Early Diagnosis; Engineering; Ensure; Equipment; Event; Exposure to; Future; Goals; Gold; HIV; HIV Infections; HIV diagnosis; Human; Human immunodeficiency virus test; Image; Individual; Infection; Label; Lectin; Maintenance; Membrane Proteins; Microfluidics; Microscopy; Molecular Conformation; Monitor; Names; Outcome; Patients; Performance; Persons; Phase; Plasma; Polysaccharides; Prevention; RNA; Reagent; Sampling; Sensitivity and Specificity; Specificity; Spottings; Surface; Technology; Testing; Time; Training; Validation; Variant; Viral; Viral Antigens; Viral Load result; Virion; Virus; Virus Diseases; acute infection; antiretroviral therapy; assay development; base; biobank; cost; diagnostic assay; fluorescence imaging; improved; low and middle-income countries; next generation; novel; pandemic disease; point-of-care diagnostics; prevent; programs; prototype; rapid diagnosis; self diagnosis; uptake; viral RNA; viral rebound

Abstract We propose to develop an advanced rapid point of care diagnostic for HIV. This approach will leverage a novel D4 diagnostic assay platform: The D4 is so named because of the chain of events that occur upon addition of blood: (1) Dispense blood onto chip; (2) Dissolution of “soluble” detection reagent spots (3) Diffusion of coated virion across a surface and binding to specific capture Ab spots; (4) Detection of binding with fluorescence imaging. We will enhance HIV virion capture using a lectin, Griffithsin, which can bind to the glycan shield of HIV virions spikes and induce exposure of CD4 binding sites which can be captured by antibodies. Individual virions can be captured, labelled and imaged using next generation cell phone based microscopy. This diagnostic test enables not only rapid “window independent” diagnosis independent of patient antibodies, but also potentially for routine viral load monitoring.

抽象的 我们建议开发一种先进的艾滋病毒快速护理点诊断方法。这种方法将 利用新型 D4 诊断检测平台：D4 之所以如此命名，是因为其链 添加血液时发生的事件： (1) 将血液分配到芯片上； (2)“可溶”的溶解 检测试剂点 (3) 包被病毒颗粒在表面扩散并与特异性结合 捕获抗体点； (4)用荧光成像检测结合。我们将增强艾滋病病毒粒子 使用凝集素 Griffithsin 进行捕获，该凝集素可以与 HIV 病毒粒子刺突的聚糖盾结合， 诱导可被抗体捕获的 CD4 结合位点的暴露。单个病毒体可以 使用下一代基于手机的显微镜进行捕获、标记和成像。这 诊断测试不仅能够实现独立于患者的快速“独立窗口”诊断 抗体，但也有可能用于常规病毒载量监测。