Photonic Crystal Based Point-of-Care Detection of HIV Viral Load Using a Smartphone Biosensor

使用智能手机生物传感器进行基于光子晶体的 HIV 病毒载量即时检测

• 批准号: 9231263
• 负责人: Kenneth Long
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9231263
• 关键词: AIDS/HIV problem; Address; Affect; Africa South of the Sahara; Antibodies; Area; Bedside Testings; Biological; Biological Assay; Biosensor; Blood; Blood specimen; CD4 Lymphocyte Count; Cellular Phone; Characteristics; Chemistry; Clinical; Clinics and Hospitals; Communication; Communities; Country; Crystallization; Custom; Data; Detection; Developed Countries; Developing Countries; Development; Devices; Diagnosis; Diagnostic; Disease; Disease Progression; Drug toxicity; Electricity; Enzyme-Linked Immunosorbent Assay; Epidemiology; Equipment; Fingers; Frequencies; Gold; Guidelines; HIV; HIV Envelope Protein gp120; HIV Seropositivity; HIV-1; Hour; Human immunodeficiency virus test; Immobilization; Immunoassay; Infection; Information Dissemination; Intervention; Left; Liquid substance; Location; Measurement; Measures; Methodology; Methods; Microfluidic Microchips; Microfluidics; Monitor; Nucleic Acid Amplification Tests; Opportunistic Infections; Optics; Patient Monitoring; Patient risk; Patients; Plasma; Prevention; Printing; Proteins; Reader; Refractive Indices; Regimen; Research Infrastructure; Resistance development; Resolution; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Signal Transduction; Societies; Specimen; Surface; System; Systems Analysis; Techniques; Temperature; Testing; Translating; Viral Load result; Virion; Virus; Whole Blood; World Health Organization; antiretroviral therapy; base; cost; data sharing; density; design; drug development; fighting; global health; instrument; laboratory development; manufacturing process; mathematical ability; miniaturize; pandemic disease; photonics; point of care; point-of-care diagnostics; portability; prototype; public health relevance; response; sample collection; sensor; young woman

 DESCRIPTION (provided by applicant): The HIV/AIDS pandemic is one of the single greatest global health challenges of contemporary society that disproportionally affects young women, especially in many of the world's poorest regions. With 25 million dead and another 35 million infected, prevention, diagnosis, and treatment are all crucial components of any plan to curb the disease. While no cure exists, antiretroviral therapies (ART) have proven successful in slowing down the progression of the disease by maintaining low numbers of virus inside patients so that their CD4 counts are maintained at levels which can successfully fight off opportunistic infections. The World Health Organization (WHO) has identified Viral Load (VL) testing as the preferred method to monitor patients on ART; however, current gold-standard techniques rely on nucleic-acid testing which are dependent on expensive, technically challenging equipment with a requirement for infrastructure such as stable electricity and temperature control. The inability to perform VL testing in many of the areas most heavily affected by the disease has left hospitals and clinics to rely on less-accurate diagnostics. This proposal seeks to develop a point of care testing solution that will address the needs of clinicians and patients across the world who do not have access to VL testing. The proposed solution will sense the number of virus particles in a 100 µL sample of patient blood using a microfluidic chip attached to a photonic crystal which is read by a custom optical cradle attached to a standard smartphone and sensitive down to at least 200 copies/mL, 5x below the WHO established threshold for ART monitoring. To accomplish this, a self-referencing optical cradle will be designed based upon working proof-of-concept prototypes that will then be characterized for both spectral resolution and sensitivity to biological attachment using the interactions between HIV-1 gp120 and anti-gp120. A microfluidic chip will be designed on top of a photonic crystal (PC) biosensor to decrease the working volumes, increase sensitivity, and increase ease-of-use. This system will then be tested on spiked patient plasma samples to quantify a limit of detection (LOD) for the device. Further improvements of the LOD will be achieved by further miniaturizing the microfluidics device through a manufacturing process based upon electrohydrodynamic-jet printing, and refractive-index based signal amplifying molecules. Finally, whole blood samples will be used to determine a new LOD and samples from HIV positive and negative patients will be used to validate the utility of the system.

 描述（由适用提供）：艾滋病毒/艾滋病大流行是当代社会最大的全球健康挑战之一，它对年轻妇女产生了不成比例的影响，尤其是在世界上许多最贫穷地区。有2500万人死亡，另外3500万人感染，预防，诊断和治疗都是任何计划遏制该疾病的关键组成部分。尽管不存在治愈，但事实证明，抗逆转录病毒疗法（ART）通过保持患者内部病毒数量少，以使其CD4计数保持在可以成功抗击机会感染的水平，从而成功地降低了疾病的发展。世界卫生组织（WHO）已将病毒载荷（VL）测试确定为监测ART患者的首选方法；但是，当前的黄金标准技术依赖于核酸测试，这些测试取决于昂贵的，技术上具有挑战性的设备，其对基础设施的要求，例如稳定的电力和温度控制。无法在许多受该疾病影响最严重影响的领域进行VL测试，这使医院和诊所无法依靠较低的诊断。该提案旨在开发一种护理点测试解决方案，该解决方案将满足世界上无法获得VL测试的临床医生和患者的需求。所提出的溶液将使用附着在光子晶体上的微流体芯片中的100 µL患者血液样本中的病毒颗粒数量，该芯片由附着在标准智能手机上的自定义光学摇篮读取，并敏感到至少200份/ml，在WHO建立的艺术监测threshold下方的5倍以下5倍。为此，将根据概念验证原型设计自我引用的光学摇篮，然后使用HIV-1 GP120和抗GP120之间的相互作用来表征光谱分辨率和对生物附着的敏感性。微流体芯片将在光子晶体（PC）生物传感器的顶部设计，以减少工作量，提高灵敏度并提高易用性。然后，将对峰值患者血浆样品进行测试，以量化设备的检测极限（LOD）。通过基于电水动力射流打印以及基于折射率的信号放大分子的制造过程，将通过制造过程进一步微型微流体设备来实现LOD的进一步改进。最后，将使用全血样品来确定新的LOD，并将使用HIV阳性和阴性患者的样本来验证系统的实用性。