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3,300万人患有艾滋病毒的人，其中96％的人居住在发展中国家。虽然HIV抗逆转录病毒疗法有效且越来越可用，但对治疗的定量监测对于为患者提供适当的护理以及控制全球抗药性HIV菌株的出现和传播是必要的。对于资源有限的设置，迫切需要进行此类测试，以避免与耐药性和转变为二线和第三线疗法相关的医疗保健成本增加。但是，当前廉价，定性，是/否诊断工具无法指导治疗或监测耐药性，并且当前基于定量的PCR测定需要昂贵的设备和复杂的环境，并在资源限制的设置中不适合护理点（POC）。另外，对于大多数POC方法，分离和浓缩病毒RNA是具有挑战性的。 SlipChip是PI实验室的高度创新技术，它独特地结合了高水平的性能与制造和操作的简单性。芯片由两个移动或“滑动”的板组成，相对于彼此，由与样品流体不混溶的流体润滑，还提供了对表面化学的控制并防止交叉污染。滑动在两个板上和失与接触中的井中进行诊断测定，并且可以在同一芯片上执行次数超过7个数量级（例如从100 pl到1 ml）的体积的操作。该滑板将促进i）上游样品制剂的整合，以ii）使用“数字”（单分子）检测使用等温扩增化学，并使用III III）下游信号放大来启用简单的读数。 包括PI，CO-PIS以及一套多样化的工业和全球健康合作者的团队具有跨越创新的微技术开发的专业知识与美国以及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在全球健康的正确背景下以及可以廉价地制造并在资源有限的设置中使用的化学，一次性设备和设备进行。 由弗朗西斯·柯林斯（Francis Collins）阐明的NIH五个优先事项中的两个优先事项的POC设备的开发适合于NIH的两个优先事项中的两个，这将对全球健康产生重大影响，并且有可能最终降低美国的医疗保健成本。从长远来看，这项工作将导致SlipChip平台作为“破坏性创新”，以通过降低成本来改善医疗保健，并简化基于核酸的分子诊断的可用性和适用性。 公共卫生相关性：全球超过3,300万人患有艾滋病毒，其中大多数在资源有限的环境中，抗逆转录病毒药物变得越来越广泛；但是，如果没有用于监测抗报告药物的患者病毒负荷的技术，则将出现和扩散HIV的耐药菌株。这项工作将开发一个基于滑移的平台，以廉价地在护理点测量HIV病毒负荷，仅仅是为了防止因抗药性HIV的出现和传播而造成的全球医疗保健灾难。这项工作还可能在美国采取“破坏性技术”，以改善医疗保健并降低成本。