SBIR Phase I: Ultra-High Throughput COVID-19 Serology Test Using a Novel Biomarker Multiplexing System

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是创建一种快速、廉价和超高通量的测试方法，以筛选患者针对导致COVID-19的SARS-CoV-2病毒的抗体。拟议的检测方法将有助于在全人群范围内筛查之前的接触情况，使流行病学家和政策制定者了解病毒的传播情况和无症状病例的频率。个人将了解自己的风险水平（例如，免疫力强的人可能在短期内不会再次感染），从而做出明智的决定。拟议的技术将是一种定量测试，可以使免疫水平与疾病严重程度或其他参数相关联。提议的测试可以很容易地同时查询多种抗原，以解决更复杂的医学评估。除了目前的大流行之外，这种灵活的技术将有助于从流行病学到疫苗开发等各种应用中对各种病原体和免疫原进行暴露检测。这个小企业创新研究（SBIR）一期项目探索了一种超高通量血清学检测的新方法。简单地说，将用荧光标记的COVID-19抗原查询高密度患者样本阵列，以识别具有SARS-CoV-2病毒抗体的患者。拟建项目：优化样品制备和排列（打印）技术和工作流程。检测探针（Covid-19抗原）和条件将使用加标样品和从商业上购买的患者血清进行优化，这些血清是从商业上购买并去鉴定的。该检测的敏感性和特异性将使用抗covid（50个样本）和非反应性（100个样本）血清进行测量。最后，鉴于SARS-CoV-2病毒与其他冠状病毒有关，其中一些冠状病毒经常在人类中传播，将确定测定探针与针对先前（即非covid）感染产生的抗体交叉反应的可能性。拟议工作的结果将为大规模平行的人群水平血清学筛查提供概念证明。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。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to create a rapid, inexpensive, and ultra-high throughput test to screen patients for antibodies against the SARS-CoV-2 virus that causes COVID-19. The proposed test will facilitate population-wide screening for prior exposure, giving epidemiologists and policy-makers insight into the virus's spread and the frequency of asymptomatic cases. Individuals will understand their levels of risk (e.g., someone with strong immunity may be protected from re-infection in the near-term) to make informed decisions. The proposed technology will be a quantitative test, which may allow immunity level to be correlated with disease severity or other parameters. The proposed test can be adapted easily to query multiple antigens simultaneously to address more complex medical assessments. Beyond the current pandemic, this flexible technology will be useful for exposure testing for diverse pathogens and immunogens in applications ranging from epidemiology to vaccine development.This Small Business Innovation Research (SBIR) Phase I project explores a novel method for ultra-high throughput serology testing. Briefly, high density arrays of patient samples will be queried with fluorescently labeled COVID-19 antigens to identify patients with antibodies against the SARS-CoV-2 virus. For the proposed project: Sample preparation and arraying (printing) techniques and workflows will be optimized. Assay probes (Covid-19 antigens) and conditions will be optimized using spiked samples and commercially purchased sera from patients, purchased commercially and deidentified. The assay's sensitivity and specificity will be measured using anti-COVID (50 samples) and non-reactive (100 samples) sera. Finally, given that the SARS-CoV-2 virus is related to other coronaviruses––some of which regularly circulate in humans, the potential for assay probes to cross-react with antibodies raised against previous (i.e., non-COVID) infections will be determined. The results of the proposed work will provide proof-of-concept for massively parallel, population-level serology screening.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.