CenBRAIN, School of Engineering, Westlake University, China.
Dept. of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.
Biosens Bioelectron. 2022 May 15;204:114054. doi: 10.1016/j.bios.2022.114054. Epub 2022 Feb 3.
In this study, we report two fiber optic-biolayer interferometry (FO-BLI)-based biosensors for the rapid detection of SARS-CoV-2 neutralizing antibodies (NAbs) and binding antibodies (BAbs) in human serum. The use of signal enhancer 3,3'-diaminobenzidine enabled the detection of NAbs, anti-receptor binding domain (anti-RBD) BAbs, and anti-extracellular domain of spike protein (anti-S-ECD) BAbs up to as low as 10 ng/mL in both buffer and 100-fold diluted serum. NAbs and BAbs could be detected individually over 7.5 and 13 min, respectively, or simultaneously by prolonging the detection time of the former. The protocol for the detection of BAbs could be utilized for detection of the RBD-N501Y variant with equal sensitivity and speed. Results of the NAbs and the anti-RBD BAbs biosensors correlated well with those of the corresponding commercial assay kit. Clinical utility of the two FO-BLI biosensors were further validated using a small cohort of samples randomly taken from 16 enrolled healthy participants who received inactivated vaccines. Two potent serum antibodies were identified, which showed high neutralizing capacities toward RBD and pseudovirus. Overall, the rapid automated biosensors can be used for an individual sample measurement of NAbs and BAbs as well as for high-throughput analysis. The findings of this study would be useful in COVID-19 related studies in vaccine trials, research on dynamics of the immune response, and epidemiology studies.
在这项研究中,我们报告了两种基于光纤生物层干涉(FO-BLI)的生物传感器,用于快速检测人血清中的 SARS-CoV-2 中和抗体(NAbs)和结合抗体(BAbs)。使用信号增强剂 3,3'-二氨基联苯胺,我们能够检测到低至 10 ng/mL 的 NAbs、抗受体结合域(anti-RBD)BAbs 和抗刺突蛋白胞外域(anti-S-ECD)BAbs,无论是在缓冲液中还是在 100 倍稀释的血清中。NAbs 和 BAbs 可以分别在 7.5 分钟和 13 分钟内单独检测,或者通过延长前者的检测时间来同时检测。用于检测 BAbs 的方案也可以用于检测 RBD-N501Y 变体,具有相同的灵敏度和速度。NAbs 和抗-RBD BAbs 生物传感器的检测结果与相应的商业检测试剂盒的检测结果相关性良好。我们还使用从 16 名接受灭活疫苗的随机招募的健康参与者中随机抽取的小样本队列进一步验证了这两种 FO-BLI 生物传感器的临床实用性。鉴定出两种有效的血清抗体,它们对 RBD 和假病毒具有高中和能力。总的来说,这种快速自动化的生物传感器可用于单个样本的 NAbs 和 BAbs 测量以及高通量分析。本研究的结果将有助于 COVID-19 相关研究,包括疫苗试验、免疫反应动力学研究和流行病学研究。