Wearable Eye Patch Paper Biosensor for Sensitive Dual-Modal Quantification of Cortisol and Dehydroepiandrosterone in Human Tear: A Noninvasive Point-of-Care Depression Screening

Depression, a pervasive mental disorder, imposes a substantial global health and economic burden. Existing diagnostic practices rely heavily on subjective clinical interviews and rating scales, lacking an objective, rapid, and early screening approach. In this work, we developed a wearable eye patch-based paper biosensor capable of highly sensitive, simultaneous quantification of cortisol and dehydroepiandrosterone (DHEA) in human tears via a competitive immunoassay format. This innovative biosensor requires only a single tear drop (∼20 μL) and a rapid 9 min analysis time, offering a noninvasive and user-friendly method for monitoring these critical biomarkers associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation─a pivotal pathophysiological feature of depression. The biosensor incorporates sulforhodamine B (SRB)-loaded, antibody-modified liposomes for target recognition and signal amplification, achieving dual-mode fluorescent and colorimetric detection. Quantitative analysis is accomplished through smartphone-based RGB value extraction. The biosensor exhibited wide detection ranges for cortisol and DHEA with low limits of detection (12 pg/mL for cortisol and 14 pg/mL for DHEA via fluorescence; 0.25 ng/mL for cortisol and 0.27 ng/mL for DHEA via colorimetry). Tear detection of the human subjects is performed using the proposed method, and the results strongly correlate with those from ELISA assay kits, confirming the biosensor's clinical feasibility and precision for cortisol and DHEA profiling. The results show the great potential and versatility of the proposed eye patch biosensor for noninvasively detecting tear-based depression biomarkers, paving the way for home-based depression screening, early identification, and prompt intervention.