Novel observation of SEIRA and SERS in aluminum-doped ZnO–BSA protein corona complexes

We report that aluminum-doped zinc oxide (AZO) nanoparticles can serve as effective platforms for surface-enhanced infrared absorption (SEIRA) and Raman scattering (SERS) in biomolecular analysis. AZO nanoparticles (average crystal size ∼16 nm), synthesized via a solvothermal method, exhibited a distinct localized surface plasmon resonance (LSPR) in the mid-infrared region, enabling strong confinement of electromagnetic fields in biomolecular vibrational fingerprint regions. Notably, these doped nanoparticles displayed SERS activity, a feature absent in undoped ZnO. Structural characterization confirmed successful Al incorporation into the ZnO wurtzite lattice, accompanied by an increased free carrier concentration responsible for the observed plasmonic behavior. We systematically studied the interaction of these plasmonic nanoparticles with bovine serum albumin (BSA). Dynamic light scattering, zeta potential, atomic force microscopy, and fluorescence quenching measurements confirmed the formation of stable AZO–BSA protein corona complexes. Fourier-transform infrared (FTIR) analysis revealed significantly enhanced amide I and II vibrational bands of BSA (up to 13-fold intensity increase) when BSA was adsorbed on the AZO surface, indicating a strong SEIRA effect via coupling to the nanoparticle LSPR. Additionally, Raman spectroscopic measurements showed clear SERS signal enhancement from the BSA in the AZO corona. These results provide clear experimental evidence that doped semiconductor nanostructures can support SEIRA and SERS in protein–nanoparticle complexes. Overall, AZO nanoparticles emerge as a promising low-cost, biocompatible alternative to noble metals for label-free biosensing and studies of protein–nanoparticle interfaces. • Al-doped ZnO nanocrystals exhibit a strong mid-infrared LSPR, not present in undoped ZnO, enabling infrared field enhancement. • AZO nanoparticles form stable complexes with BSA proteins (confirmed by DLS, zeta potential, AFM, etc.), creating a well-defined protein corona interface for spectroscopy. • Adsorbed BSA shows amide I and II infrared absorption signals enhanced up to 13-fold on AZO surfaces, demonstrating a clear surface-enhanced IR absorption effect. • Raman spectroscopic measurements shows SERS signal enhancement from the BSA in the AZO corona • The AZO–BSA system validates Al-doped ZnO as a low-cost, biocompatible alternative to noble metals for SEIRA, suitable for label-free biosensing of proteins and other biomolecules. • This work provides the first experimental evidence of SEIRA/SERS using doped semiconductor nanoparticles with a protein corona, opening new pathways for infrared biosensors and nanoparticle–protein interaction studies.