Smartphone-based diagnostic for HIV self-testing

基于智能手机的 HIV 自检诊断

• 批准号: 10455110
• 负责人: Jacqueline Linnes
• 金额: $ 69.36万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-06 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10455110
• 关键词: Acquired Immunodeficiency Syndrome; Adopted; Adoption; Africa; Algorithms; Anthropology; Antibodies; Awareness; Biological Assay; Biosensor; Blood; Blood specimen; Car Phone; Cellular Phone; Chronic; Clinical; Clinical Research; Clinical Trials; Cost Savings; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Diffusion; Ensure; Equipment; Evaluation; Fluorescence; Goals; Gold; HIV; HIV Infections; HIV Seropositivity; Hand; Health; Health Care Costs; Health Personnel; Human; Human immunodeficiency virus test; Immunoassay; Immunology; Indiana; Individual; Kenya; Label; Laboratories; Laboratory Technicians; Measures; Mediating; Medical; Methods; Microfluidic Microchips; Microfluidics; Microprocessor; Monitor; Motion; Nucleic Acids; Outcome; Pathogen detection; Patients; Performance; Persons; Phase; Plasma; Positioning Attribute; Power Sources; Preparation; Process; Quality of life; Rapid diagnostics; Reproducibility; Resolution; Running; Sampling; Sensitivity and Specificity; Technology; Testing; Time; United States; Universities; Viral; Viral Antigens; Viral Load result; Virus; Visit; Whole Blood; Work; algorithm development; amplification detection; antiretroviral therapy; barrier to care; base; care providers; clinically relevant; commercialization; compliance behavior; connected care; cost; design; detection limit; detection platform; holistic approach; implementation barriers; improved; in vitro Assay; insight; interdisciplinary approach; intimate behavior; isothermal amplification; medical schools; molecular diagnostics; novel strategies; particle; pathogen; point of care; point-of-care diagnostics; prevent; prospective; prospective test; prototype; remote health care; scale up; self testing; smartphone Application; transmission process; usability; viral detection

SUMMARY ABSTRACT The 90-90-90 Target endorsed by UNAIDS, proposes diagnosing 90% of people infected with HIV worldwide, engaging 90% of them on effective antiretroviral treatment, and ensuring that 90% of those treated achieve sustained viral load suppression by 2020. The United States is woefully unprepared to reach this target; only 30% of HIV infected individuals in the U.S. currently achieve viral load suppression. Clearly, a paradigm shift in viral load testing will be required to accomplish this goal. This proposal aims to create a quantitative, handheld, viral load self-test that can be used by patients themselves to support their management of this chronic condition and that delivers relevant clinical insights to remote healthcare providers. Building on our preliminary work, the objective of the R61 phase is to combine isothermal loop- mediated nucleic acid amplification (LAMP) with a highly sensitive and label-free readout method called particle diffusometry for quantification of HIV viral load in a hand held platform with minimal process steps. Specific milestones include: 1) optimization of LAMP assays to ensure the lowest possible limit of detection, 2) optimization of a microfluidic test chip for minimal sample prep, 3) algorithm development and testing to obtain real-time viral detection. Assessment of usability and stakeholder needs with our partners at Moi University (Moi) in Eldoret, Kenya, and Indiana University School of Medicine (IUSM) in Indianapolis, Indiana will ensure that the handheld platform and HIV test will be readily adopted by stakeholders. At the conclusion of the R61 phase we will have a platform that is ready for implementation testing. The objective of the R33 phase is to develop a proof-of-concept device that is validated in small manufacturing runs and fully assessed against clinical performance metrics in plasma and whole blood. The handheld platform and test chips will be evaluated for process control reproducibility and an initial pilot clinical study will be performed with banked or prospectively collected samples from HIV patients at IUSM and Moy University. The outcome of this R33 Phase will be a highly characterized, sensitive, quantitative handheld HIV viral load detection platform that performs robustly with real clinical samples and is ready for scale up. Completion of these objectives will position us for FDA pre-submission and regulatory approval, rapid scale up, and implementation of a highly accurate HIV viral load self-test in the U.S. and East Africa. By enabling patients to monitor their HIV viral load while remaining connected to healthcare provider support, we will help to reduce barriers to treatment compliance and ultimately increase the number of patients with sustained viral load suppression as called for by the UNAIDS 90-90-90 targets.

摘要摘要 90-90-90的目标是由UNAID认可的，提议诊断90％的全球感染HIV的人， 将其中90％的人参与有效的抗逆转录病毒治疗，并确保有90％的治疗方法达到 到2020年，持续的病毒负荷抑制。仅有的 美国目前有30％的艾滋病毒感染者正在接受病毒负荷抑制。显然，范式转变 需要进行病毒载荷测试来实现此目标。该建议旨在创建一个定量的手持台 病毒负载自我测试可以由患者本身用于支持他们对这一慢性的管理 条件并为远程医疗保健提供者提供相关的临床见解。 在我们的初步工作的基础上，R61阶段的目的是结合等温循环 - 介导的核酸扩增（LAMP），具有高度敏感且无标签的读数方法称为 粒子扩散测量法，以最小的过程步骤定量HIV病毒载荷。 特定的里程碑包括：1）灯测定的优化以确保最低检测极限，2） 优化微流体测试芯片，用于最小样品准备，3）算法开发和测试以获得 实时病毒检测。与MOI大学合作伙伴一起评估可用性和利益相关者需求 （MOI）在肯尼亚的Eldoret和印第安纳州印第安纳波利斯的印第安纳大学医学院（IUSM）将确保 利益相关者将很容易采用手持式平台和艾滋病毒测试。在R61结束时 阶段我们将拥有一个准备实施测试的平台。 R33阶段的目的是开发一种概念验证设备，该设备在小型中验证 制造业运行并完全评估了血浆和全血的临床性能指标。这 将对手持式平台和测试芯片进行评估，以进行过程控制可重复性和初始的试点临床 研究将通过IUSM和MOY的HIV患者的库存或前瞻性收集的样本进行研究 大学。该R33期的结果将是一个高度特征，敏感的，定量的手持hiv 病毒载荷检测平台可在实际临床样本中执行鲁棒性，并且可以进行扩展。 这些目标的完成将使我们为FDA预提取和监管批准，快速 在美国和东非，扩大并实施高度准确的HIV病毒负荷自我测试。经过 使患者能够监测其HIV病毒负荷，同时保持与医疗保健提供者的支持，我们 将有助于减少治疗依从性的障碍，并最终增加 UNIADS 90-90-90目标要求持续的病毒载荷抑制。

项目成果

Quantifying Brownian motion in the presence of simple shear flow with particle diffusometry.

• DOI: 10.1007/s00348-022-03566-8
• 发表时间: 2023
• 期刊: Experiments in fluids
• 影响因子: 2.4

PD-LAMP smartphone detection of SARS-CoV-2 on chip.

• DOI: 10.1016/j.aca.2022.339702
• 发表时间: 2022-04-22
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: Colbert AJ;Lee DH;Clayton KN;Wereley ST;Linnes JC;Kinzer-Ursem TL
• 通讯作者: Kinzer-Ursem TL

A smartphone-based particle diffusometry platform for sub-attomolar detection of Vibrio cholerae in environmental water.

• DOI: 10.1016/j.bios.2020.112497
• 发表时间: 2020-11-01
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Moehling TJ;Lee DH;Henderson ME;McDonald MK;Tsang PH;Kaakeh S;Kim ES;Wereley ST;Kinzer-Ursem TL;Clayton KN;Linnes JC
• 通讯作者: Linnes JC