摘要：

新冠病毒（SARS-CoV-2）的持续流行严重影响全球人类健康，高传染性和较强的变异能力可能导致SARS-CoV-2与人类长期共存。甲型流感病毒（FluA）感染与新型冠状病毒肺炎（COVID-19）均会出现发烧、干咳和疲劳等流感样症状（ILI, influenza-like illness），仅依据症状几乎无法将SARS-CoV-2早期感染者与FluA感染者区分。SARS-CoV-2大流行和FluA流行季节重叠可能会使大量人口面临同时感染这两种病毒的高风险。多份病例报告显示，相比于单一病毒感染，SARS-CoV-2 与FluA的 共感染患者会迅速出现严重的临床症状。因此，发展快速、灵敏区分SARS-CoV-2 和FluA感染者的检测技术对于ILI患者的管理、治疗和防控疫情扩散具有重要价值。龙峰教授团队与解放军疾病预防控制中心合作研发了新型光纤免疫传感技术，实现新冠与流感病毒现场快速检测。Journal of Medical Virology以封面论文的形式发表了题为“Rapid and universal detection of SARS‐CoV‐2 and influenza A virus using a reusable dual‐channel optic fiber immunosensor”的研究论文。首都医科大学郝荣章教授、解放军疾病预防控制中心宋宏彬研究员和中国人民大学龙峰教授为本论文的共同通讯作者。

在该研究中，构建了一种基于倏逝波传感技术的双通道光纤生物传感技术平台（DOFIS），该传感器采用免疫竞争检测方法和流动相检测模式检测流感样症状患者样本。分别固定在两根光纤表面的SARS-CoV-2的刺突蛋白和FluA的核蛋白与样本中的病毒蛋白竞争性地捕获工作溶液中Cy5.5标记抗体；沿光纤表面传导的倏逝波激发光纤表面捕获的抗体上的Cy5.5，产生荧光信号，信号强度与样本中的病毒量成反比。通过集成化的流动相进样模块和荧光检测模块，DOFIS可实现自动化检测。该论文不仅研究了DOFIS技术的检测动力学性能，同时采用了甲型流感病毒和SARS-CoV-2假病毒系统评估了DOFIS技术的性能，并且在新冠疫情防控现场验证了DOFIS对临床样本的检测能力。结果表明，DOFIS可识别多种SARS-CoV-2变异株和主要流感病毒毒株，灵敏度和特异性均优于商业化的ELISA和胶体金试纸，对SARS-CoV-2 奥密克戎临床样本的特异性和灵敏度分别达到100%和94%。基于集成化的设计和可再生光纤，本研究的DOFIS生物传感平台可实现低成本的自动化检测。另外，DOFIS尺寸小巧，操作简单，有望用于社区传染病快速鉴别诊断和自动化监测，有助于社区或资源有限地区的疫情防控工作。

Abstract：

Establishment of rapid on-site detection technology capable of concurrently detecting SARS-Cov-2 and influenza A virus is urgent to effectively control the epidemic from these two types of important viruses. Accordingly, we developed a reusable dual-channel optical fiber immunosensor (DOFIS), which utilized the evanescent wave-sensing properties and tandem detection mode of the mobile phase, effectively accelerating the detection process such that it can be completed within 10 min. It could detect the nucleoprotein of multiple influenza A viruses (H1N1, H3N2, and H7N9), as well as the spike proteins of the SARS-CoV-2 Omicron and Delta variants, and could respond to 20 TCID50/ml SARS-CoV-2 pseudovirus and 100 TCID50/ml influenza A (A/PR/8/H1N1), presenting lower limit of detection and wider linear range than enzyme-linked immunosorbent assay. The detection results on 26 clinical samples for SARS-CoV-2 demonstrated its specificity (100%) and sensitivity (94%), much higher than the sensitivity of commercial colloidal gold test strip (35%). Particularly, DOFIS might be reused more than 80 times, showing not only cost-saving but also potential in real-time monitoring of the pathogenic viruses. Therefore, this newly-developed DOFIS platform is low cost, simple to operate, and has broad spectrum detection capabilities for SARS-CoV-2 mutations and multiple influenza A strains. It may prove suitable for deployment as a rapid on-site screening and surveillance technique for infectious disease.

Keywords：SARS-Cov-2, Influenza A, Dual-channel optical fiber immunosensor, Real-time monitoring

DOFIS检测SARS-CoV-2和FluA的原理示意图

发表于Journal of Medical Virology 2022, 94,5325（最新影响因子为20.693）

文章链接：https://onlinelibrary.wiley.com/doi/10.1002/jmv.28015