Thermoplasmonic Regulation and <i>In Situ</i> Detection of Biomolecules with a Photothermal-Enhanced Plasmonic Biosensing System

Label-free biosensing via plasmonic near-fields is a promising tool for quantitative analysis of biomolecular substances for disease diagnosis, pathogen biodefense, and environmental monitoring. For complex samples, however, the competence of molecular sensing with plasmonics is hampered by nonspecific interferences. The near-field thermoplasmonic effect, characterized by an interrelated and synergistic phenomenon of Localized Surface Plasmon Resonance (LSPR), empowers the potential multifunctionality of plasmonic biosensing. This work presented the photothermal-enhanced plasmonic (PTEP) sensing system, which enabled near-field photothermal heating regulation, <i>in situ</i> temperature monitoring, biomolecular regulation, and parallel biosensing at the plasmonic interface. The photothermal near-fields constructed through homogenized laser excitation were characterized and thermoregulated <i>in situ</i> by the PTEP system with a high spatiotemporal resolution. Notably, the proposed PTEP biosensor system exhibited improved sensitivity attributed to the thermoplasmonic-enhanced refractive index contrast. Moreover, precise spatiotemporal programming of the thermoplasmonic field contributed to active antifouling and specific identification of target molecules. Based on the PTEP biosensors, a thermoplasmonic biosensing strategy was proposed for rapid analysis of trace IL-6 molecules in complex cerebrospinal fluid samples from mouse models, with a detection limit down to 0.1 pM. Our proposed PTEP biosensing method offers a versatile and adaptable strategy that potentially enhances the functionality and utility of nanoplasmonic biosensors.