Rapid and accurate detection technology is significant for screening on population scale and control of infectious diseases. The dilution and contamination of samples can affect the accuracy of response signal, resulting in false positives, which makes diagnosis challenging, especially for early patients with mild symptoms. Here, an AuNPs@Ta 2 C-M/Au/TFBG sensor with saturation sites was reported for specific detection of pathogen taking SARS-CoV-2 as an example. Homogeneous periodic AuNPs@Ta 2 C-M structure was deposited on Au film-coated TFBG by a photo-induced method to further extend the SPR performance and surface plasmon polaritons (SPPs) response range. The ssDNA probes are immobilized on the sensing platform in a higher density using a double modification method to solve the targets concealment problem caused by the spatial secondary conformational structure of long sequence nucleic acids. Synergistic effect between the high-density probes and multi-plasmon structure enables a noticeable improvement in hybridization efficiency and signal transduction of trace target sequences. The experimental results demonstrate that the sensor can accurately detect 30 clinic samples within 5 min without amplification, which shows high agreement with RT-PCR (Kappa index = 1). In particular, dilution kinetic experiments with clinical single samples (LOD:2 pg/ml) and 10-in-1 pooled sample (Maximum dilution ratio:10 5 ) validates the excellent trace analysis capability of the sensor. Overall, this bio-sensing method provides a promising approach for trace detection of infectious pathogens.