In this study, a surface-enhanced Raman spectroscopy (SERS) magnetic sensor is established based on SERS principle and magnetic separation technology, and a highly sensitive, simple and fast method for quantitative detection of neutralizing antibodies (nABs) and specific IgG of SARS-CoV-2 in plasma is established combined with immunoassay. Two kinds of Raman nanospheres (RNPs) with different characteristic Raman shifts are used as signal sources and coupled to ACE2 and anti-IgG (FC) antibodies respectively, and magnetic beads are coupled to RBD. The competitive relationship between ACE2 and nABs, the binding relationship between specific IgG and anti-IgG (FC) antibodies are determined. The results show that the concentrations of nABs and specific IgG in the range of 10-2000 ng mlare well correlated with SERS response intensity, and the recoveries are both between 90%-110%, with good precision. Bilirubin and common anticoagulants have no interference on the detection results. This method is accurate, reliable, sensitive and does not require complex pre-treatment, and is expected to be used for simultaneous detection of nABs and specific IgG in plasma of SARS-CoV-2. It has guiding significance for the development and evaluation of vaccines and the formulation of individualized vaccination schedule.
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