SERS-Active Nanocomposite Contact Lenses for Label-Free Multiplexed Biosensing of Tear Analytes

Abstract Continuous monitoring remains limited by the fact that most wearable biosensors are built around single-analyte recognition chemistries, even though many physiological states are defined by changes across multiple metabolites. Tear fluid is one of the most biochemically informative biofluids accessible non-invasively, but contact lens biosensors have largely relied on enzymatic or electrochemical techniques that are difficult to extend beyond one target marker at a time. Here, we report a label-free surface-enhanced Raman spectroscopy (SERS)-active contact lens in which gold nanostars are grown in situ on commercial hydrogel contact lenses. The resulting gold nanostar-loaded contact lens (AuNS-CL) introduces a plasmonic sensing layer directly onto the wearable substrate, with a substrate-averaged SERS enhancement factor of ∼105, while preserving the lens’ physiochemical properties. Quantitative biosensing was demonstrated using a digital thresholding method to account for variable hotspot distributions. Metabolites such as lactate and urea were quantified through their diagnostic bands in several solutions, including artificial tears and a mixture of tear analytes. The AuNS-CLs showed a strong linear response in the physiological range and recovery errors below 10%. To the best of our knowledge, this is the first demonstration of a wearable contact lens for label-free SERS quantification of tear metabolites.