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: 8064597
• 负责人: RUSTEM F ISMAGILOV
• 金额: $ 33.35万
• 依托单位: UNIVERSITY OF CHICAGO
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8064597
• 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; 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，而且越来越容易获得，但必须对治疗进行定量监测，以便为患者提供适当的护理，并控制艾滋病毒抗药性菌株在全世界的出现和传播。资源有限的环境迫切需要此类测试，以避免与耐药性和转向二线和三线治疗相关的医疗保健费用惊人增加。然而，目前廉价的、定性的、是/否的诊断工具不能指导治疗或监测耐药性，并且目前基于PCR的定量测定需要昂贵的设备和复杂的环境，不适合资源有限的环境中的护理点（POC）。此外，分离和浓缩病毒RNA对于大多数POC方法来说是具有挑战性的。 SlipChip是PI实验室的一项高度创新的技术，独特地将高性能与简单的制造和操作相结合。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，还提供表面化学控制并防止交叉污染。滑动使两个板中的威尔斯孔接触和分离以执行诊断测定，并且可以在同一芯片上进行超过7个数量级（例如从100 pL到1 mL）的体积范围的操作。滑动芯片将促进以下的整合：i）上游样品制备，以分离和浓缩病毒RNA; ii）通过使用等温扩增化学的“数字”（单分子）检测的核酸扩增来定量病毒颗粒; iii）下游信号扩增，以实现简单的读出。 该团队包括主要研究者、共同研究者以及各种工业和全球卫生合作者，其专业知识涵盖创新微技术的开发、RNA分子生物学和恒温核酸扩增、诊断测定的临床应用、FDA批准的诊断测试的开发和传播、一次性塑料的制造、填充和包装、诊断设备的制造在美国、印度和尼日利亚与艾滋病患者一起工作。该团队将确保所有研究都是在正确的全球健康背景下以及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POC设备来监测HIV病毒载量符合NIH主任弗朗西斯柯林斯阐述的五个优先事项中的两个：它将对全球健康产生重大影响，并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平台成为一种“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：全世界有3 300多万人感染艾滋病毒，其中大多数人生活在资源有限的环境中，而抗逆转录病毒药物的供应越来越广泛;然而，如果没有监测服用抗逆转录病毒药物的患者体内病毒载量的技术，艾滋病毒的耐药性菌株就会出现和传播。这项工作将开发一个基于SlipChip的平台，以低廉的成本在护理点测量HIV病毒载量，并简单地防止耐药HIV的出现和传播造成的全球卫生保健灾难。这项工作也可能在美国作为一种“颠覆性技术”来改善医疗保健并降低成本。