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

RAPID：开发超灵敏热对比放大侧流免疫测定法，用于快速即时诊断 COVID-19

• 批准号: 2029474
• 负责人: John Bischof
• 金额: $ 20万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2029474&HistoricalAwards=false
• 关键词: RAPID; Development; ultrasensitive; thermal; contrast

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.

创新和独特的热对比技术将被用于检测激光照射的纳米金颗粒产生的热量，以极大地提高用于检测和诊断新冠肺炎的快速诊断测试(即横向流动分析)的灵敏度。这项技术已被用于显著改进艾滋病毒、疟疾、链球菌和流感的横向流动检测，将使新冠肺炎能够进行广泛、廉价(每项检测1美元)、快速(≤10分钟)、医疗保健点检测。这种检测不存在，也不能使用目前的方法同时检测新冠肺炎感染的早期(即病毒蛋白)和晚期(即抗体)。这些新的热对比侧向血流分析，以及新的热对比“读数”技术，将加快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。虽然这项技术将首先在临床环境中部署，但预计这项技术最终可以在学校、机场、体育和娱乐赛事，甚至在家里用于评估新冠肺炎和其他传染病的感染和传播。拟议中的研究将开发新的侧向流动分析方法，与创新的热对比技术一起用于高灵敏度、低成本、医疗点检测新冠肺炎。从长远来看，这一新模式将应用于多种疾病。侧向流动分析可以说是世界上最便宜、最快、最容易使用的快速诊断分析方法。虽然它们被定性地用于多种疾病，但它们有弱点，包括缺乏敏感度和疾病负担的量化。这两个问题都通过我们的新型热对比分析技术得到了解决。为了专门针对新冠肺炎解决这一问题，提出了两种方法：1)优化金纳米颗粒和侧向流动分析，以结合新冠肺炎蛋白或新冠肺炎抗体分析物；2)使用称为“结合比率”的新量化优值系数，为优化的热对比侧向流动分析快速识别试剂和成分。该项目是与行业合作伙伴的更大努力的一部分，目的是扩大专有热对比读取器的制造规模，使其能够负担得起医生办公室、紧急护理机构、急诊室和野战医院等临床点环境。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Ultrasensitive and Highly Specific Lateral Flow Assays for Point-of-Care Diagnosis

• DOI: 10.1021/acsnano.0c10035
• 发表时间: 2021-02-19
• 期刊: ACS NANO
• 影响因子: 17.1
• 作者: Liu, Yilin;Zhan, Li;Bischof, John C.
• 通讯作者: Bischof, John C.