Digital SlipChip Technology for POC and Resource-Limited Viral Load Measurements

用于 POC 和资源有限的病毒载量测量的数字滑动芯片技术

• 批准号: 8308073
• 负责人: RUSTEM F ISMAGILOV
• 金额: $ 16.48万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308073
• 关键词: Acquired Immunodeficiency Syndrome; Address; Algorithms; Anti-Retroviral Agents; Automation; Biological Assay; Blood Tests; Care Technology Points; Caring; Cartoons; Cellular Phone; Chemistry; Clinical; Collaborations; Complex; Detection; Development; Devices; Diagnostic; Diagnostic Equipment; Diagnostic tests; Disposable Equipment; Drug resistance; Engineering; Ensure; Environment; Equipment; Evolution; FDA approved; Goals; HIV; HIV Seropositivity; HIV drug resistance; HIV-1; Health Care Costs; Healthcare; Human immunodeficiency virus test; Image; India; Industrial Health; Industry; Knowledge; Laboratories; Lead; Life; Liquid substance; Measurement; Measures; Molecular; Molecular Biology; Monitor; NASBA Analysis; Nigeria; Nucleic Acid Amplification Tests; Nucleic Acids; Patients; Pattern; Performance; Pharmaceutical Preparations; Plasma; Plastics; Preparation; Problem Solving; Process; Protocols documentation; RNA; RNA amplification; Reader; Reagent; Relative (related person); Research; Research Infrastructure; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Signal Transduction; Surface; System; Technology; Testing; Time; United States National Institutes of Health; Viral; Viral Load result; Viral load measurement; Whole Blood; Work; antiretroviral therapy; base; cost; design; digital; global health; improved; innovation; innovative technologies; internal control; meetings; operation; particle; point of care; prevent; programs; prototype; public health relevance; resistant strain; single molecule; tool; viral RNA

DESCRIPTION (provided by applicant): HIV is a significant global health problem- recent estimates suggest ~33 million people living with HIV, with 96% residing in the developing world. While HIV antiretroviral therapy is effective and increasingly available, quantitative monitoring of treatment is necessary to provide proper care to patients, and to control the emergence and spread of drug-resistant strains of HIV worldwide. Such tests are urgently needed for resource-limited settings to avoid staggering increases in health care costs associated with drug resistance and switching to second- and third-line therapies. However, current inexpensive, qualitative, yes/no diagnostic tools cannot guide treatment or monitor drug resistance, and current quantitative PCR-based assays require expensive equipment and complex environments unsuitable for point-of-care (POC) in resource-limited settings. Additionally, isolating and concentrating viral RNA is challenging for most POC approaches. The SlipChip is a highly innovative technology from the PI's laboratory that uniquely combines a high level of performance with simplicity of fabrication and operation. The chip consists of two plates that move- or "slip"- relative to one another, lubricated by a fluid that is immiscible with the sample fluid and also provides control of surface chemistry and prevents cross-contamination. Slipping brings wells in the two plates in and out of contact to execute a diagnostic assay, and manipulations of volume ranging over 7 orders of magnitude (e.g. from 100 pL to 1 mL) can be performed on the same chip. The SlipChip will facilitate integration of i) upstream sample preparation to isolate and concentrate viral RNA with ii) quantification of viral particles via nucleic acid amplification using "digital" (single molecule) detection using isothermal amplification chemistries, with iii) downstream signal amplification to enable simple readout. The team that includes PI, co-PIs and a diverse set of industrial and global health collaborators has expertise spanning development of innovative micro-technologies, to molecular biology of RNA and isothermal nucleic acid amplification, to clinical use of diagnostic assays, to development and dissemination of FDA- approved diagnostics tests, to manufacturing, filling and packaging of plastic disposables, to manufacturing of diagnostic equipment, to working with AIDS patients both in the US and in India and Nigeria. This team would ensure that all research is done in the correct context of global health and in the context of chemistries, disposables, and equipment that can be manufactured inexpensively and used in resource-limited settings. The development of a POC device to monitor HIV viral loading fits within two of the five priorities of the NIH as articulated by Director Francis Collins: it will have a large impact on global health, and it has the potential to ultimately reduce healthcare costs in the US. Long term, this work would lead to SlipChip platform as a "disruptive innovation" to improve healthcare by reducing costs, and simplifying and increasing availability and applicability of nucleic acid-based molecular diagnostics. PUBLIC HEALTH RELEVANCE: Over 33 million people worldwide are living with HIV, the majority of them in resource-limited settings, with anti- retroviral drugs becoming more and more widely available; however, without technologies for monitoring viral load in patients on anti-retroviral drugs, drug resistant strains of HIV will emerge and spread. This work will develop a SlipChip-based platform to measure the HIV viral load at the point of care inexpensively and simply to prevent a global health care catastrophe caused by emergence and spread of drug-resistant HIV. This work is also likely to act in the US as a "disruptive technology" to improve healthcare and reduce costs.

描述（由申请人提供）：艾滋病毒是一个重大的全球健康问题 - 最近的估计表明约有 3300 万人感染艾滋病毒，其中 96% 居住在发展中国家。虽然艾滋病毒抗逆转录病毒疗法是有效的并且越来越容易获得，但必须对治疗进行定量监测，以便为患者提供适当的护理，并控制全球艾滋病毒耐药株的出现和传播。在资源有限的环境中迫切需要进行此类测试，以避免与耐药性和转向二线和三线疗法相关的医疗保健成本急剧增加。然而，当前廉价、定性、是/否诊断工具无法指导治疗或监测耐药性，并且当前基于定量 PCR 的检测需要昂贵的设备和复杂的环境，不适合资源有限环境中的即时护理 (POC)。此外，分离和浓缩病毒 RNA 对于大多数 POC 方法来说都具有挑战性。 滑动芯片是 PI 实验室的一项高度创新技术，它将高水平的性能与制造和操作的简单性独特地结合在一起。该芯片由两个相对移动或“滑动”的板组成，由与样品流体不混溶的流体润滑，并且还提供表面化学控制并防止交叉污染。滑动使两个板中的孔接触和脱离接触以执行诊断测定，并且可以在同一芯片上执行超过 7 个数量级的体积操作（例如从 100 pL 到 1 mL）。滑动芯片将促进以下整合：i) 上游样品制备，以分离和浓缩病毒 RNA；ii) 使用等温扩增化学物质的“数字”（单分子）检测，通过核酸扩增对病毒颗粒进行定量；以及 iii) 下游信号放大，以实现简单的读数。 该团队包括 PI、共同PI 和各种工业和全球健康合作者，其专业知识涵盖创新微技术的开发、RNA 和等温核酸扩增的分子生物学、诊断测定的临床使用、FDA 批准的诊断测试的开发和传播、一次性塑料用品的制造、填充和包装、诊断设备的制造、 与美国、印度和尼日利亚的艾滋病患者一起工作。该团队将确保所有研究都是在全球健康的正确背景下以及在可以廉价制造并在资源有限的环境中使用的化学品、一次性用品和设备的背景下进行的。 开发用于监测 HIV 病毒载量的 POC 设备符合 NIH 主任弗朗西斯·柯林斯 (Francis Collins) 所阐述的 NIH 五个优先事项中的两个：它将对全球健康产生巨大影响，并且有可能最终降低美国的医疗保健成本。从长远来看，这项工作将使滑动芯片平台成为一项“颠覆性创新”，通过降低成本、简化和提高基于核酸的分子诊断的可用性和适用性来改善医疗保健。 公共卫生相关性：随着抗逆转录病毒药物的普及，全世界有超过 3300 万人感染艾滋病毒，其中大多数生活在资源有限的环境中；然而，如果没有监测抗逆转录病毒药物患者病毒载量的技术，艾滋病毒耐药株就会出现并传播。这项工作将开发一个基于滑动芯片的平台，以低廉的成本在护理点测量艾滋病病毒载量，并简单地防止耐药艾滋病毒的出现和传播造成的全球医疗灾难。这项工作也可能在美国作为改善医疗保健和降低成本的“颠覆性技术”发挥作用。