High-throughput serological assay for detection of cytokines/chemokines in COVID-19 patients

用于检测 COVID-19 患者细胞因子/趋化因子的高通量血清学检测

• 批准号: 555017-2020
• 负责人: Winnik, Mitchell
• 金额: $ 3.64万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=705335
• 关键词: throughput; serological; assay; detection; cytokines

COVID-19 is a novel viral illness, with a wide spectrum of clinical illness from asymptomatic to critical illness and death. The immune response to the virus may play an important role in the ultimate clinical outcome. It has been hypothesized that an inflammatory overactivity or "cytokine storm" may drive clinical deterioration in severe COVID-19. Patients with high levels of inflammation (or cytokines) have been found to have more severe disease and are more likely to die. It is therefore essential for us to unravel the inflammatory response to COVID-19, both to identify patients at-risk for deterioration and to define potential thresholds for initiation of therapies that target the immune response. In order to do this, we need technologies to rapidly, efficiently, accurately measure cytokine levels. We aim to develop a technology, rooted in novel materials chemistry, to measure cytokine levels and as well antibodies against the SARS-CoV-2 antibody. This technology is based on the preparation of micrometre-sized plastic beads encoded with different metal atoms in which each encoded bead surface is coated with a capture biomolecule (antibody or antigen) to bind disease biomarkers from biological fluids collected from COVD-19 patients. In this way we can detecting 8 different cytokines in each patient sample. The technology can be expanded to detect 32 cytokines and antibodies in each sample. It also allows one to use secondary sample barcoding in order to analyze up to 20 patient samples in single test, where results can be acquired within a 1-hour timeframe. Upon development and deployment of this technology, we will use clinical samples from patients with COVID-19 to characterize the immune response and to conduct "serosurveillance" to identify and characterize patients who have been previously infected with COVID-19.

COVID-19是一种新型病毒性疾病，临床疾病谱广泛，从无症状到危重病和死亡。对病毒的免疫应答可能在最终的临床结果中起重要作用。据推测，炎症性过度活动或“细胞因子风暴”可能导致严重COVID-19的临床恶化。炎症（或细胞因子）水平高的患者被发现患有更严重的疾病，更有可能死亡。因此，我们必须解开对COVID-19的炎症反应，以识别有恶化风险的患者，并确定启动针对免疫反应的治疗的潜在阈值。 为了做到这一点，我们需要快速，有效，准确地测量细胞因子水平的技术。我们的目标是开发一种技术，植根于新材料化学，以测量细胞因子水平以及针对SARS-CoV-2抗体的抗体。该技术基于制备用不同金属原子编码的微米大小的塑料珠，其中每个编码的珠表面涂覆有捕获生物分子（抗体或抗原），以结合来自COVD-19患者的生物流体的疾病生物标志物。通过这种方式，我们可以在每个患者样本中检测8种不同的细胞因子。该技术可以扩展到检测每个样本中的32种细胞因子和抗体。它还允许使用二次样本条形码，以便在单次测试中分析多达20个患者样本，其中可以在1小时的时间范围内获得结果。在开发和部署这项技术后，我们将使用COVID-19患者的临床样本来表征免疫反应，并进行“血清监测”，以识别和表征先前感染COVID-19的患者。