Synergistic Electromagnetic Enhancement and Graphene-Induced Molecular Enrichment for Mid-Infrared Detection of Proteins

Surface-enhanced infrared absorption spectroscopy (SEIRAs) holds immense potential for trace biomolecular detection. Here, we report a high-performance SEIRAs biosensing platform based on a two-dimensional (2D) monolayer graphene/nanostructured metal metasurface hybrid heterostructure. The platform synergistically couples deep-subwavelength nanoscale electromagnetic hotspots with 100 nm inter-unit gaps with nanomaterial-induced interfacial molecular enrichment. The hybrid sensor amplifies the vibrational fingerprint signals of immunoglobulin G at characteristic amide bands, achieving a low detection concentration down to 3 pM. Furthermore, protein spike-and-recovery assays in unprocessed artificial sweat and urine yield excellent recovery rates. Density functional theory calculations reveal that graphene provides a seamless, non-site-specific π−π physisorption matrix, effectively relieving interfacial steric repulsion and maximizing molecular coverage within plasmonic hotspots. This work provides a robust theoretical framework and an innovative experimental paradigm for the development of next-generation, highly sensitive mid-infrared biosensing technologies.