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产生的热量，从而大大提高用于检测和诊断COVID-19的快速诊断测试（即横向流动试验）的灵敏度。该技术已被用于显著改善艾滋病毒、疟疾、链球菌和流感的横向流动检测，将使COVID-19的广泛、廉价（1美元/次）、快速（≤10分钟）、即时检测成为可能。目前尚不存在这种检测方法，也无法使用现有方法检测COVID-19感染的早期（即病毒蛋白）和晚期（即抗体）阶段。这些新的热对比横向流动测定法，连同新的热对比“读取”技术，将加速对疾病传播和管理的有效和有针对性的检测和监测，并为国家和全球社会带来巨大利益。虽然首次部署将在临床环境中，但预计这项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横向流动分析，与创新的热对比技术一起用于高灵敏度、低成本的COVID-19即时检测。从长远来看，这种新模式将适用于各种各样的疾病。横向流动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，但它们存在弱点，包括缺乏对疾病负担的敏感性和量化。这两个问题都可以通过我们新颖的热对比分析技术来解决。为了专门针对COVID-19解决这一问题，提出了两种方法：1)优化金纳米颗粒和横向流动分析方法，以结合COVID-19蛋白或COVID-19抗体分析物；2)使用称为“结合比率”的新型定量指标，快速识别用于优化热对比横向流动分析的试剂和组分。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读取器的生产规模，使其在医生办公室、紧急护理环境、急诊室和野战医院等护理点临床环境中都能负担得起。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.