RAPID: Development of an ultrasensitive thermal contrast amplification lateral flow immunoassay for rapid, point-of-care COVID-19 diagnosis

创新和独特的热对比技术将用于检测激光照射的金纳米颗粒的热量，以极大地提高旨在检测和诊断COVID-19的快速诊断测试（即侧向流测定）的灵敏度。这项技术已被用于显著改善艾滋病毒、疟疾、链球菌和流感的侧流检测，将使COVID-19的广泛、廉价（1美元/检测）、快速（≤ 10分钟）、即时检测成为可能。使用目前用于检测COVID-19感染早期（即病毒蛋白）和晚期（即抗体）的方法，这种检测不存在，也不可能存在。这些新的热对比侧向流测定，沿着新的热对比“阅读”技术，将加速有效和有针对性的检测和疾病传播和管理的监测，并为国家和全球社会带来巨大的利益。 虽然首次部署将在临床环境中进行，但预计该技术最终可用于学校，机场，体育和娱乐活动，甚至在家中评估COVID-19和其他传染病的感染和传播。拟议的研究将开发新的侧流测定，与创新的热对比技术一起使用，用于高度敏感，廉价，COVID-19的即时检测。从长远来看，这一新模式将适用于各种疾病。侧流分析可以说是世界上最便宜、最快和最容易使用的快速诊断分析。 虽然它们被定性地用于许多疾病，但它们有缺点，包括缺乏敏感性和疾病负担的量化。 这两个问题都通过我们的新型热对比分析技术得到解决。为了特别针对COVID-19解决这一问题，提出了两种方法：1）优化金纳米颗粒和侧流测定以结合COVID-19蛋白或COVID-19抗体分析物，以及2）使用称为“结合比”的新定量品质因数来快速鉴定用于优化热对比侧流测定的试剂和组分。该项目是与行业合作伙伴共同努力的一部分，旨在扩大专有热对比阅读器的制造规模，使其适用于医疗点临床环境，如医生办公室，紧急护理环境，急诊室，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响进行评估，被认为值得支持审查标准。

Innovative and unique thermal contrast technology will be used to detect heat from laser irradiated gold nanoparticles to vastly improve the sensitivity of rapid diagnostics tests (i.e. lateral flow assays) designed to detect and diagnose COVID-19. This technology, which has been used to significantly improve lateral flow assays for HIV, malaria, Strep and influenza, will enable widespread, inexpensive ( $1/test), rapid (≤ 10 minutes), point-of-care detection of COVID-19. Such detection does not exist and cannot exist using the current methodologies for detecting both early (i.e. viral protein) and late (i.e. antibody) stages of COVID-19 infection. These new, thermal contrast lateral flow assays, along with new thermal contrast “reading” technology, will accelerate effective and targeted testing and surveillance of disease spread and management and bring enormous benefits to both national and global society. While first deployment will be in clinical settings, it is envisioned that this technology can eventually be used at schools, airports, sporting and entertainment events and even at home to assess the infection and spread of COVID-19 and other infectious diseases.The proposed research will develop new lateral flow assays to be used with innovative thermal contrast technology for highly sensitive, inexpensive, point-of-care detection of COVID-19. This new paradigm will, in the long term, be applied to a wide variety of diseases. Lateral flow assays are arguably the cheapest, fastest and easiest to use rapid diagnostic assays in the world. While they are used qualitatively for numerous diseases, they have weaknesses that include lack of sensitivity and quantification of disease burden. Both of these issues are addressed through our novel Thermal Contrast Assay technology. To address this specifically for COVID-19, two approaches are proposed: 1) optimizing gold nanoparticles and lateral flow assays for binding either COVID-19 protein or COVID-19 antibody analytes, and 2) the use of a new quantitative figure of merit called the “Binding Ratio” to rapidly identify reagents and components for optimized thermal contrast lateral flow assays. This project is part of a larger effort with industry partners to scale up the manufacturing of a proprietary thermal contrast reader so that it will be affordable for point-of-care clinical settings such as doctors’ offices, urgent care settings, emergency rooms, and field hospitals.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.