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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.more » « lessFree, publicly-accessible full text available March 27, 2026
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