Smartphone-based POC Testing for HIV Using Glowstick Chemistry

基于智能手机的 HIV 使用荧光棒化学进行 POC 测试

基本信息

批准号：
10594143
负责人：
Richard Willson
金额：
$ 45.65万
依托单位：
UNIVERSITY OF HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-06 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10594143
关键词：
Acids Address Adolescent Affinity African American Android Antibodies Antigen-Antibody Complex Archives Avidity Binding Blood Bulla Cellular Phone Chemicals Chemistry Clinic Clinical Collaborations Communicable Diseases Detection Development Diagnostic Diagnostic Procedure Dissociation Early Diagnosis Early treatment Ensure Enzyme-Linked Immunosorbent Assay Epitopes Fibronectins Fluorescence Polarization Formulation Goals HIV HIV Infections HIV Seropositivity HIV diagnosis Health Health system Hispanic Home Human Human immunodeficiency virus test Immunoassay Infection Instruction Interruption Kinetics Lateral Libraries Ligands Light Link Liquid substance Materials Testing Measurement Medical Modeling Monitor Optics Patients Performance Persons Phage Display Phase Population Population Heterogeneity Populations at Risk Readability Reading Reagent Reporter Research Resources Risk Sampling Source Specimen Technology Testing Time Translating Viral Load result Visit Work acute infection analog antigen detection antiretroviral therapy biobank cohort cost demographics detection limit falls fluorophore high risk improved innovation insight lateral flow assay manufacture member novel particle pediatric human immunodeficiency virus point of care pre-exposure prophylaxis prevent protein biomarkers quality assurance recruit scaffold seal self testing seroconversion test strip transmission process usability

项目摘要

Effective testing for HIV allows for detection of acute infections (new and rebound), appropriate antiretroviral treatment, suppression of viral load, and interruption of transmission. However, early detection of infection or regular self-monitoring at point-of-need or at home remains a challenge. Lateral flow assays are a well-established, inexpensive point-of-need diagnostic method, and commonly are favored when applicable because of their ease of use and low cost. Where they most commonly fall short is in analytical sensitivity, notably in antigen-detection diagnostics for infectious diseases. Our goal is to develop radically-improved LFAs by implementing the inexpensive, shelf-stable chemi-excitation chemistry of glow sticks in a point-of-care format to excite fluors without light or optical filters. Our preliminary results suggest this chemistry enables LFAs with greatly improved limits of detection (very low pg/mL), using a standard smartphone with a $2 adaptor and no sophisticated optical components. Our central hypothesis is that our novel, reagent-optimized chemi-excited lateral flow assay technology integrated with a storage-stable reagent cartridge and readable with a smartphone will lead to a new, widely-useful and potentially very-superior class of highly-sensitive lateral flow assays. We will test this hypothesis through 5 specific aims: (1) Development of a highly-sensitive and easily-usable lateral flow assay for HIV p24 in human blood, including development of novel avidity-enhanced dual-fibronectin-domain binders, (2) Immune complex dissociation (ICD) for rebound/breakthrough HIV diagnosis, (3) Testing with 300 negative and archived-positive human samples from diverse cohorts, (4) To evaluate clinical performance using fresh samples from patients and usability with a diverse population of subjects at high risk of HIV infection/rebound (R33 Phase), (5) Easier usability by more people, quality assurance for test items (R33 Phase).

有效的艾滋病毒检测可以检测急性感染（新发感染和反弹感染），适当抗逆转录病毒治疗、抑制病毒载量和阻断传播。然而，早在需要时或在家中检测感染或定期自我监测仍然是一个挑战。侧流式检测是一种成熟、廉价的按需诊断方法，通常用于由于其易于使用且成本低廉，因此在适用时受到青睐。他们最常跌倒的地方缺点是分析灵敏度，特别是在传染病的抗原检测诊断中。我们的目标是通过实施廉价、货架稳定的方法来开发从根本上改进的 LFA 即时检测形式的荧光棒化学激发化学，无需光或光学即可激发荧光体过滤器。我们的初步结果表明，这种化学作用使 LFA 的极限大大提高检测（非常低的 pg/mL），使用带有 2 美元适配器的标准智能手机，并且没有复杂的光学器件成分。我们的中心假设是我们新颖的、试剂优化的化学激发侧流检测技术与储存稳定的试剂盒集成，可通过智能手机读取将导致一种新的、广泛使用的、可能非常优越的高灵敏度侧向流动化验。我们将通过 5 个具体目标来检验这一假设：（1）开发高度敏感且易于使用的侧向层析检测人体血液中的 HIV p24，包括开发新型亲合力增强的双纤连蛋白结构域结合物，(2) 免疫复合物解离 (ICD) 反弹/突破性 HIV 诊断，(3) 对 300 名阴性和存档阳性的人类进行检测来自不同队列的样本，(4) 使用患者的新鲜样本评估临床表现以及对 HIV 感染/反弹高风险的不同人群的可用性（R33 阶段），(5) 更多人更容易使用，测试项目的质量保证（R33阶段）。