SERS Detection of SARS‐CoV‐2 Spike Proteins and IgG Antibodies Using Metallic <i>H</i> ‐type Nano‐Apertures

ABSTRACT The rapid and accurate detection of viral biomarkers is critical for controlling infectious disease outbreaks, as highlighted by the COVID‐19 pandemic. Here, we present a label‐free platform for the ultrasensitive detection of SARS‐CoV‐2 spike protein and IgG antibodies in liquid using surface‐enhanced Raman spectroscopy (SERS) based on an array of plasmonic H ‐shaped nano‐apertures. The nanostructure is designed to support a resonance at 777.8 nm. The Raman signal of both biomolecules was recorded at several locations on the nanostructure under off‐resonance laser excitation at 785 nm, confirming its reproducibility. The designed nanostructure enables limit of detection of 0.85 ng/mL in a liquid environment, without the need for complex surface functionalization or labeling. Using principal component analysis (PCA), we successfully distinguished between spike protein, IgG antibodies, and their mixtures, highlighting the platform's ability to analyze complex biological matrices. This work advances the development of sensitive SERS‐based biosensors for the rapid and accurate detection of emerging pathogens in liquid environments.