Microneedle-integrated distance-based paper device for simultaneous transdermal detection of cortisol and dopamine

Accurate measurement of stress marker cortisol and neurotransmitter dopamine is essential for understanding the physiological effects of chronic stress, enabling early therapeutic interventions to prevent adverse health consequences. Herein, we introduce the first fully integrated wearable device comprising a microneedle (MN) patch and distance-based paper analytical device (dPAD) for minimally invasive dermal interstitial fluid (ISF) sampling and simultaneous cortisol and dopamine sensing. The MN patch employs a swellable hydrogel matrix for efficient ISF extraction, whereas the simple dPAD sensor can simultaneously detect cortisol and dopamine through colorimetric reactions. Quantitative analysis was achieved through simple measurement of the colored distance proportional to the analyte concentration using a ruler. The device demonstrates high sensitivity, with detection limits of 0.25 μg mL⁻¹ for cortisol and 1.0 ng mL⁻¹ for dopamine, along with excellent selectivity for both analytes. It also exhibited high accuracy and precision, with recovery rates of 98.5–100.7% for cortisol and 98.8–102.2% for dopamine. These results show that the developed sensor device is user-friendly, simplifies the analysis process, reduces costs, and eliminates the need for complex instrumentation, making it a promising tool for point-of-care (POC) testing for stress and its relative disorders, with potential applications in diagnosing other biomarkers.