Ultrasensitive, Rapid, Amplification-Free RNA Virus Detection Using Nanodimer-Based Nucleic Acid Target Sequence Recognition

使用基于纳米二聚体的核酸靶序列识别进行超灵敏、快速、无扩增的 RNA 病毒检测

• 批准号: 2232940
• 负责人: Jiang Zhe
• 金额: $ 43.53万
• 依托单位: University of Akron
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2232940&HistoricalAwards=false
• 关键词: Ultrasensitive; Rapid; Amplification; Free; RNA

Ribonucleic acid (RNA) viruses are a major threat to public health and global economy. Numerous human diseases, from the common colds to life-threatening hemorrhagic fevers are caused by RNA viruses. In the past decades, RNA viruses such as human immune deficiency virus, Ebola virus, dengue virus, and most recently coronavirus (COVID-19) impose significant burdens on global health and global economy. Rapid and high-sensitivity detection of the presence of RNA viruses in human specimens and the environment is crucial to track the rate of viral contamination, prevent fast spreading, and establish preventive measures and timely administration of treatments. The popular polymerase chain reaction (PCR)-based virus detection takes lengthy turn-around time and requires specialized laboratory instruments and trained personnel. This project aims to create a novel biosensing microsystem that can provide ultra-sensitive, rapid and reliable detection of RNA viruses with no need of PCR amplification. The project will result in a portable, rapid, economical RNA virus detection method for point-of-care-testing, pandemic prevention, anti-bioterrorism, and environmental monitoring. Furthermore, this cross-disciplinary research will support the development of a diverse cohort of graduate, undergraduate students at the University of Akron. The research results will also support several graduate-level courses on microsystems and biomaterials at the University of Akron.The technical scope of the project are divided into multiple tasks: 1) create a surface acoustic pre-filtering chip that will rapidly remove microscale impurities in continuous flow, which would otherwise cause clogging of the sensing channels, 2) research a novel nanoparticle focusing method based on unique electro-diffusio-phoresis effect, which can significantly increases the virion concentration and thus output signals thousands of times within seconds, 3) research a virus detection chip based on an innovative nanodimer dissociation assay, which in principle, can detect viruses with single virus resolution, 4) research unique signal multiplexing applied on a resistive pulse sensor array, which will enable high throughput, digital detection of RNA viruses, and ultimately 5) integrate the three chips into a microsystem and demonstrate its utility for rapid detection of ultra-low abundance RNA viruses using an inactivated model virus. The research will advance the field of virus detection with ultra-high resolution and digitization capability, which are difficult to achieve using current state-of-the-art methods. It will also generate numerous new knowledges and innovations for the development of the next generation high-throughput, onsite biosensing systems in general.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

核糖酸（RNA）病毒是对公共卫生和全球经济的主要威胁。从普通感冒到威胁生命的出血发烧，许多人类疾病是由RNA病毒引起的。在过去的几十年中，RNA病毒（例如人类免疫缺陷病毒，埃博拉病毒，登革热病毒）以及最近的冠状病毒（Covid-19）对全球卫生和全球经济造成了巨大负担。快速和高敏性检测人类标本中RNA病毒的存在和环境对于跟踪病毒污染的速度，防止快速扩散并建立预防措施并及时地治疗至关重要。流行的聚合酶链反应（PCR）基于基于的病毒检测需要很长的转弯时间，需要专门的实验室仪器和训练有素的人员。该项目旨在创建一个新型的生物传感微型系统，该系统可以提供对RNA病毒的超敏感，快速和可靠的检测，而无需PCR扩增。 该项目将导致一种可移植的，快速，经济的RNA病毒检测方法，用于护理点测试，大流行预防，抗生素恐怖主义和环境监测。此外，这项跨学科的研究将支持阿克伦大学（University of Akron）的各种研究生，本科生的各种各样的发展。 The research results will also support several graduate-level courses on microsystems and biomaterials at the University of Akron.The technical scope of the project are divided into multiple tasks: 1) create a surface acoustic pre-filtering chip that will rapidly remove microscale impurities in continuous flow, which would otherwise cause clogging of the sensing channels, 2) research a novel nanoparticle focusing method based on unique电 - 扩散剂量效应，可以显着增加病毒率浓度，因此输出信号在几秒钟内信号数千次，3）研究基于创新的纳米二聚体分离测定的病毒检测芯片，原则上可以检测到与单个病毒的启用电阻式脉冲传感器的启用，它可以检测到与单个病毒的启用良好的启用电阻式数组，该传感器能够检测到的病毒，4）最终5）将三个芯片整合到一个微型系统中，并使用灭活的模型病毒证明了其快速检测超低丰度RNA病毒的实用性。 这项研究将通过超高分辨率和数字化能力来推进病毒检测领域，使用当前的最新方法很难实现。它还将为下一代高通量，现场生物传感系统的发展产生许多新的知识和创新。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的智力优点和更广泛的影响来通过评估来支持的。