Photothermal Recycling Biosensing for Continuous, Sensitive Molecular Quantification

Continuous biochemical sensing provides valuable insights into an individual's physiological state and the mechanisms underlying pathophysiological changes. However, most existing bioanalytical methods are not compatible with continuous biochemical sensing. A major technical challenge lies in achieving rapid measurement readouts while maintaining high specificity and sensitivity in complex biological fluids. Sensitive molecular detection typically requires slow analyte-binder dissociation and long incubation to reach equilibrium, whereas rapid and frequent measurements demand fast association-dissociation kinetics that are difficult to reconcile for low-abundance analytes. To address this challenge, we introduce a sensing mechanism termed photothermal recycling (PTR), which mimics the thermal cycling process in polymerase chain reactions. Using plasmonic photothermal effects, PTR rapidly recycles binders to enable frequent measurements. We demonstrate a digital PTR assay capable of multi-hour biochemical monitoring with sub-picomolar (pM) sensitivity in buffer, diluted serum, and saliva. This approach leverages localized thermal energy to dynamically modulate biomolecular recognition, offering a new bioanalytical paradigm for continuous biochemical sensing across diverse application settings.