The rapid spread of COVID-19 including recent emergence of new variants with its extreme range of pathologies create an urgent need to develop a versatile sensor for a rapid, precise, and highly sensitive detection of SARS-CoV-2. Herein, we report a microcantilever-based optical detection of SARS-CoV-2 antigenic proteins in just few minutes with high specificity by employing fluidic-atomic force microscopy (f-AFM) mediated nanomechanical deflection method. The corresponding antibodies against the target antigens were first grafted on the gold-coated microcantilever surface pre-functionalized with EDC-NHS chemistry for a suitable antibody-antigen interaction. Rapid detection of SARS-CoV-2 nucleocapsid (N) and spike (S1) receptor binding domain (RBD) proteins was first demonstrated at a clinically relevant concentration down to 1 ng/mL (33 pM) by real-time monitoring of nanomechanical signal induced by antibody-antigen interaction. More importantly, we further show high specific detection of antigens with nasopharyngeal swab specimens from patients pre-determined with qRT-PCR. The results take less than 5 min (swab to signal ≤5 min) and exhibit high selectivity and analytical sensitivity (LoD: 100 copies/ ml; 0.71 ng/ml of N protein). These findings demonstrate potential for nanomechanical signal transduction towards rapid antigen detection for early screening of SARS-CoV-2 and its related mutants.

COVID-19 的快速传播，包括最近出现的具有极端病理学特征的新变种，迫切需要开发一种多功能传感器，以快速、精确和高灵敏度地检测 SARS-CoV-2。在此，我们报告了一种基于微悬臂梁的光学检测方法，通过采用流体原子力显微镜（f-AFM）介导的纳米机械偏转方法，在短短几分钟内以高特异性对 SARS-CoV-2 抗原蛋白进行光学检测。针对目标抗原的相应抗体首先被移植到经 EDC-NHS 化学预功能化的金涂层微悬臂梁表面上，以实现合适的抗体-抗原相互作用。通过实时监测纳米机械信号，首次在低至 1 ng/mL (33 pM) 的临床相关浓度下快速检测 SARS-CoV-2 核衣壳 (N) 和刺突 (S1) 受体结合域 (RBD) 蛋白由抗体-抗原相互作用诱导。更重要的是，我们进一步展示了通过 qRT-PCR 预先确定的患者鼻咽拭子标本中抗原的高特异性检测。仅需不到 5 分钟即可获得结果（拭子到信号≤5 分钟），并表现出高选择性和分析灵敏度（LoD：100 拷贝/ml；0.71 ng/ml N 蛋白）。这些发现表明，纳米机械信号转导在快速抗原检测方面具有潜力，可用于早期筛查 SARS-CoV-2 及其相关突变体。