This work reports an efficient method to detect SARS-CoV-2 antibodies in blood samples based on SERS combined with a machine learning tool. For this purpose, gold nanoparticles directly conjugated with spike protein were used in human blood samples to identify anti-SARS-CoV-2 antibodies. The comprehensive database utilized Raman spectra from all 594 blood serum samples. Machine learning investigations were carried out using the Scikit-Learn library and were implemented in Python, and the characteristics of Raman spectra of positive and negative SARS-CoV-2 samples were extracted using the Uniform Manifold Approximation and Projection (UMAP) technique. The machine learning models used were k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Decision Trees (DTs), logistic regression (LR), and Light Gradient Boosting Machine (LightGBM). The kNN model led to a sensitivity of 0.943, specificity of 0.9275, and accuracy of 0.9377. This study showed that combining Raman spectroscopy and a machine algorithm can be an effective diagnostic method. Furthermore, we highlighted the advantages and disadvantages of each algorithm, providing valuable information for future research.
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