Plasmonic paper for point-of-care SERS biosensing of dopamine from tears

Biocompatible plasmonic paper-based substrates for surface enhanced Raman spectroscopy (SERS) represent a promising platform for tear fluid monitoring and disease diagnosis. Quantitative determination of tear dopamine levels enables differentiation between autoimmune Sjögren disease and dry eye syndromes, which is vital for fast, correct treatment. Moreover, there is a strong demand for the development of methods suitable for outpatient examination, with simple self-sampling of accessible body fluids. To address this challenge, we developed a user-friendly paper-based plasmonic biosensor. The synthesized substrate demonstrated excellent reproducibility, with relative standard deviations of 1.3% (intraday) and 3.6% (interday) using adenine as a Raman reporter molecule. The limit of detection (LOD) for adenine was remarkably low at 0.5 fg/mL. Subsequently, the substrate was applied for label-free detection of the target analyte dopamine from artificial tear fluid containing common interferents, and from basal tears. The LOD for dopamine reached a physiological level 6.3 ng/mL, low enough for differentiation of the Sjögren disease. These findings highlight the potential of SERS point-of-care biosensing of dopamine in tears, with overarching potential for various neuropsychiatric diseases.