A one-press hollow microneedle-paper patch for automated sampling-to-readout multiplexed sensing of biomarkers in interstitial fluid.

Interstitial fluid analysis offers noninvasive diagnostic potential but faces challenges in efficient sampling and multiplexed detection. Here, we present a novel one-press hollow microneedle paper-based patch (HMN-PP) for rapid (<7 min), visual, and simultaneous monitoring of glucose, uric acid, lactate, and pH in interstitial fluid. The system integrates a mechanically robust hollow microneedle array (600 μm height, 0.53 N/needle penetration force) fabricated via a scalable casting-demolding process, enabling minimally invasive fluid extraction. A 3D wax-patterned paper chip incorporates multienzyme cascade reactions (GOx/UOx/LOx) and pH-responsive dyes for selective biomarker recognition, coupled with smartphone-based colorimetric analysis. The flexible PDMS-based device seamlessly combines sampling and detection modules, achieving automated "sampling-to-readout" via single-finger compression. Validated using biomimetic skin models, the system demonstrates high accuracy with recoveries of 97.63-106.67% (glucose), 95.67-108.32% (uric acid), 93.65-105.27% (lactate), and ±0.13 pH units. This user-centric platform eliminates complex operations and external instruments, providing a promising technological pathway for future home health monitoring and personalized diagnostics.