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.

Non‐invasive biosensors have attracted attention for their potential to obtain continuous, real‐time physiological information through measurements of biochemical markers, such as one of the most important—glucose, in biological fluids. Although some optical sensing materials are used in non‐invasive devices for continuous glucose monitoring (CGM), surface or localized plasmon sensing material are seldom applied in CGM owing to modest sensitivity and bulk sensing apparatus. Herein, a metasurface (MGMSPR) biosensor based on the metasurface plasmon resonance chip modified with heterostructured Ti₃C₂ MXene−Graphene oxide (MG) is reported, which potentially enables ultra‐sensitive glucose detection. The sensor consists of a dual‐channel microfluidic device integrated with silver mirror enhanced MGMSPR chips. Not only does it promote the entry of glucose oxidase (GOD) into the internal pores and enhance the stable fixation of GOD in the membrane, but also the integration of MG material provides a high specific surface area and unique electronic properties, thereby significantly enhancing the sensitivity of the MGMSPR sensor. The detection limit of MGMSPR biosensor is 106.8 µM. This pioneering approach opens new avenues for monitoring physiological parameters and process analytical technology on an optical platform, providing continuous health monitoring and production process control through optical sensors.