Developing plasmonic biosensors that are low‐cost, portable, and relatively simple to operate remains challenging. Herein, a novel metasurface plasmon‐etch immunosensor is described, namely a nanozyme‐linked immunosorbent surface plasmon resonance biosensor, for the ultrasensitive and specific detection of cancer biomarkers. Gold‐silver composite nano cup array metasurface plasmon resonance chip and artificial nanozyme‐labeled antibody are used in two‐way sandwich analyte detection. Changes in the biosensor's absorption spectrum are measured before and after chip surface etching, which can be applied to immunoassays without requiring separation or amplification. The device achieved a limit of alpha‐fetoprotein (AFP) detection < 21.74 fM, three orders of magnitude lower than that of commercial enzyme‐linked immunosorbent assay kits. Additionally, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) are used for quantitative detection to verify the universality of the platform. More importantly, the accuracy of the platform is verified using 60 clinical samples; compared with the hospital results, the three biomarkers achieve high sensitivity (CEA: 95.7%; CA125: 90.9%; AFP: 86.7%) and specificity (CEA: 97.3%; CA125: 93.9%; AFP: 97.8%). Due to its rapidity, ease of use, and high throughput, the platform has the potential for high‐throughput rapid detection to facilitate cancer screening or early diagnostic testing in biosensing.

The sudden outbreak of COVID-19 rapidly developed into a global pandemic, which caused tens of millions of infections and millions of deaths. Although SARS-CoV-2 is known to cause COVID-19, effective approaches to detect SARS-CoV-2 using a convenient, rapid, accurate, and low-cost method are lacking. To date, most of the diagnostic methods for patients with early infections are limited to the detection of viral nucleic acids via polymerase chain reaction (PCR), or antigens, using an enzyme-linked immunosorbent assay or a chemiluminescence immunoassay. This study developed a novel method that uses localized surface plasmon resonance (LSPR) sensors, optical imaging, and artificial intelligence methods to directly detect the SARS-CoV-2 virus particles without any sample preparation. The virus concentration can be qualitatively and quantitatively detected in the range of 125.28 to 10⁶ vp/mL through a few steps within 12 min with a limit of detection (LOD) of 100 vp/mL. The accuracy of the SARS-CoV-2 positive or negative assessment was found to be greater than 97%, and this was demonstrated by establishing a regression machine learning model for the virus concentration prediction (R² > 0.95).