Streamlined 15-min HIV Viral Load Self-Testing Using Finger-Stick Blood

使用指尖采血进行简化的 15 分钟 HIV 病毒载量自检

• 批准号: 10465046
• 负责人: Yu-Hsiang Hsieh
• 金额: $ 47.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10465046
• 关键词: AIDS prevention; Accident and Emergency department; Accreditation; Acquired Immunodeficiency Syndrome; Acute; Baltimore; Biological Assay; Blood; Buffers; Car Phone; Cessation of life; Charge; Chronic Disease; Clinic; Clinic Visits; Clinical; Clinical Management; Cold Chains; Collaborations; Communicable Diseases; Complex; Consent; Consumption; Detection; Development; Devices; Drug resistance; FDA approved; Filtration; Fingers; Fluorescence; Freeze Drying; Goals; Gold; HIV; HIV Infections; Health Policy; Human immunodeficiency virus test; Infection; Institutes; Interruption; Intervention; Laboratories; Lead; Liquid substance; Magnetism; Manuals; Membrane; Methods; Microfluidics; Miniaturization; Monitor; Nucleic Acids; Patients; Performance; Persons; Phase; Plasma; Preparation; Prevention strategy; Process; Protocols documentation; Public Health; RNA; Reaction; Reagent; Recording of previous events; Rehydrations; Resource-limited setting; Sampling; Schedule; Science; Self Administration; Site; Surveys; Techniques; Technology; Test Result; Testing; Time; Training; Translating; Uganda; Venipunctures; Viral; Viral Load result; Visit; Waxes; Whole Blood; World Health Organization; acute care; acute infection; amplification detection; antiretroviral therapy; base; cost; detection assay; detection limit; diagnostic technologies; high risk population; home test; improved; instrument; instrumentation; miniaturize; multidisciplinary; novel; nucleic acid purification; operation; particle; portability; prevent; reconstitution; resistance mutation; response; seal; self testing; tool; transmission process; user-friendly; validation studies; viral rebound

The revolutionary advances in human immunodeficiency virus (HIV) antiretroviral therapy (ART) which could reach and maintain viral suppression have gradually transitioned HIV/acquired immunodeficiency syndrome (AIDS) to a manageable, chronic disease in the past 2 decades. However, it is still one of the leading public threats in the world with approximately 37.9 million people living with HIV (PLWHA), 1.7 million new infections, and 770,000 HIV-related deaths in 2018. As a comprehensive strategy for improving the clinical management of HIV, the World Health Organization (WHO) specifically calls for improved accessibility of not only ART, but also HIV testing to reach untested high-risk populations and to help PLWHA ascertain their viral load (VL) and potential for transmission. In response, this project seeks to develop a diagnostic technology for rapid, affordable and easy-to-use HIV VL detection that is amenable for self-testing and even in-home testing. Unlike conventional diagnostic technologies that are impractical for self-testing due to requirements of sophisticated devices and instruments, our platform employs magnetofluidic technology to replace bulk fluid transport with magnetic particle manipulation, enabling the integration of sample processing and PCR without the need for complex fluidic cartridges and supporting instrumentation. Miniaturization of instrumentation and assay facilitated by magnetofluidics minimizes reagent consumption and the thermal mass, leading to >10-fold reduction in cost and assay time. The integrated device facilitates HIV RNA detection from finger-stick blood in a facile “sample-to- answer” manner, promising a rapid, inexpensive and user-friendly strategy for VL self-testing. We have assembled a multi-disciplinary team with complementary expertise and strong track record and history of collaboration in team science. In order to achieve the above goal, we propose (i) to develop a streamlined assay protocol for sample processing and PCR detection of HIV in whole blood, (ii) to develop an inexpensive magnetofluidic cartridge implementing the HIV detection assay as a simple blood-to-result test, (iii) to develop a portable instrument to enable facile HIV self-testing, (iv) to develop a method for ambient cartridge storage, and finally (v) to evaluate performance and patient acceptability of the HIV self-testing platform in both acute care and resource-limited settings. The development of this HIV VL self-testing technology has the potential for dramatically increasing the accessibility of detecting acute infections and monitoring viral suppression in PLWHA, thus presenting a game changer in the global HIV prevention strategy.

人类免疫缺陷病毒(HIV)抗逆转录病毒疗法(ART)的革命性进展 达到并保持病毒抑制逐渐过渡到艾滋病毒/获得性免疫缺陷综合征 (艾滋病)在过去的20年里变成了一种可控制的慢性病。然而，它仍然是领先的公众之一 世界上约3790万艾滋病毒携带者(PLWHA)的威胁，170万新感染者， 2018年与艾滋病毒相关的死亡人数为77万人。作为一项全面的战略，以改善临床管理 关于艾滋病毒，世界卫生组织(世卫组织)特别呼吁不仅改善抗逆转录病毒药物的可及性，而且 艾滋病毒检测，以接触未经检测的高危人群，并帮助PLWHA确定他们的病毒载量(VL)和 传播的可能性。作为回应，该项目寻求开发一种快速、负担得起的诊断技术 和易于使用的艾滋病毒VL检测，这是服从自我检测，甚至在家里测试。与传统不同 诊断技术由于复杂设备的要求而不适用于自检 仪器，我们的平台采用磁流控技术，用磁粉取代散装流体运输 操作，实现了样品处理和聚合酶链式反应的集成，不需要复杂的流体 墨盒和辅助仪器。促进仪器和分析的小型化 磁流体将试剂消耗和热质量降至最低，使成本和成本降低10倍 化验时间。该集成设备便于从手指棒血中轻松地进行HIV RNA检测 Answer“方式，承诺为VL自检提供快速、廉价和用户友好的策略。 我们已经组建了一支多学科的团队，拥有互补的专业知识和良好的记录和历史 在团队科学方面的合作。为达到上述目标，我们建议(I)发展精简的 用于全血中艾滋病毒的样本处理和聚合酶链式反应检测的分析方法，(Ii)建立一种廉价的 将艾滋病毒检测化验作为简单的血液对结果测试的磁流体盒，(Iii)开发一种 便携式仪器，以实现方便的艾滋病毒自我检测，(4)开发一种环境墨盒储存方法，以及 最后(五)评估艾滋病毒自我检测平台在两种急性护理中的表现和患者的可接受性 和资源受限设置。这种HIV VL自我检测技术的开发具有以下潜力 极大地提高了检测PLWHA急性感染和监测病毒抑制的可及性， 从而改变了全球艾滋病毒预防战略的游戏规则。

项目成果

Highly Sensitive Serum Protein Analysis Using Magnetic Bead-Based Proximity Extension Assay.

使用基于磁珠的邻近延伸分析进行高灵敏度血清蛋白分析。

• DOI: 10.1021/acs.analchem.2c02684
• 发表时间: 2022
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Zhang,Pengfei;Hu,Jiumei;Park,JoonSoo;Hsieh,Kuangwen;Chen,Liben;Mao,Alan;Wang,Tza-Huei
• 通讯作者: Wang,Tza-Huei

Point-of-Care Amenable Detection of Mycoplasma genitalium and Its Antibiotic Resistance Mutations.

生殖支原体及其抗生素耐药性突变的护理点检测。

• DOI: 10.1021/acssensors.2c02630
• 发表时间: 2023
• 期刊: ACS sensors
• 影响因子: 8.9
• 作者: Chen,Fan-En;Wang,Jonathan;Nambiar,AnjuHaridas;Hardick,Justin;Melendez,Johan;Trick,AlexanderY;Wang,Tza-Huei
• 通讯作者: Wang,Tza-Huei

Magnetofluidic immuno-PCR for point-of-care COVID-19 serological testing.

• DOI: 10.1016/j.bios.2021.113656
• 发表时间: 2022-01-01
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Zhang P;Chen L;Hu J;Trick AY;Chen FE;Hsieh K;Zhao Y;Coleman B;Kruczynski K;Pisanic TR 2nd;Heaney CD;Clarke WA;Wang TH
• 通讯作者: Wang TH

A Portable Droplet Magnetofluidic Device for Point-of-Care Detection of Multidrug-Resistant Candida auris.

一种可移植的液滴磁磁体装置，用于耐多药念珠菌的护理点检测。

• DOI: 10.3389/fbioe.2022.826694
• 发表时间: 2022
• 期刊: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
• 影响因子: 5.7
• 作者: Lee, Pei-Wei;Totten, Marissa;Chen, Liben;Chen, Fan-En;Trick, Alexander Y.;Shah, Kushagra;Ngo, Hoan Thanh;Jin, Mei;Hsieh, Kuangwen;Zhang, Sean X.;Wang, Tza-Huei
• 通讯作者: Wang, Tza-Huei