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Infrared (IR) spectroscopic fingerprinting is a powerful analytical tool for characterizing molecular compositions across biological, environmental, and industrial samples through their vibrational modes. Specifically, when the sample is characterized in resonant plasmonic cavities, as in the surface-enhanced mid-IR absorption spectroscopy (SEIRAS), highly sensitive and specific molecular detection can be achieved. However, current SEIRAS techniques rely on nanofabricated sub-wavelength antennas, limited by low-throughput lithographic processes, lacking scalability to address broad biochemical sensing applications. To address this, we present an on-resonance SEIRAS method utilizing silver (Ag) cubic microparticles (Ag-CMPs) with robust mid-IR plasmonic resonances. These monocrystalline Ag-CMPs, featuring sharp edges and vertices, are synthesized via a high-throughput, wet-chemical process. When dispersed on gold mirror substrates with an aluminum oxide spacer, Ag-CMPs support enhanced near-field light-matter interactions in nanocavities while enabling far-field imaging-based optical interrogation due to their strong extinction cross-sections. We demonstrate the detection of polydimethylsiloxane (PDMS) and bovine serum albumin (BSA) monolayers by simply probing individual Ag-CMPs, enabled by the resonant amplification of the characteristic vibrational absorptions. Furthermore, our single-particle SEIRAS (SP-SEIRAS) approach effectively analyzes complex human peritoneal fluid (PF) samples, eliminating the challenges of standard bulk sample measurements. This scalable and efficient SP-SEIRAS method addresses key limitations of IR spectroscopic fingerprinting techniques, unlocking possibilities for their widespread adoption in real-world biochemical sensing applications. 

Optical metasurfaces provide solutions to label-free biochemical sensing by localizing light resonantly beyond the diffraction limit, thereby selectively enhancing light–matter interactions for improved analytical performance. However, high-Qresonances in metasurfaces are usually achieved in the reflection mode, which impedes metasurface integration into compact imaging systems. Here, we demonstrate a metasurface platform for advanced biochemical sensing based on the physics of the bound states in the continuum (BIC) and electromagnetically induced transparency (EIT) modes, which arise when two interfering resonances from a periodic pattern of tilted elliptic holes overlap both spectrally and spatially, creating a narrow transparency window in the mid-infrared spectrum. We experimentally measure these resonant peaks observed in transmission mode (Q∼734 atλ∼8.8µm) in free-standing silicon membranes and confirm their tunability through geometric scaling. We also demonstrate the strong coupling of the BIC-EIT modes with a thinly coated PMMA film on the metasurface, characterized by a large Rabi splitting (32cm⁻¹) and biosensing of protein monolayers in transmission mode. Our new photonic platform can facilitate the integration of metasurface biochemical sensors into compact and monolithic optical systems while being compatible with scalable manufacturing, thereby clearing the way for on-site biochemical sensing in everyday applications.