Paper-Droplet Hybrid Strategy for Highly Selective Blood Plasma Separation in Multiplex Diagnostics

We report a novel hybrid sessile-droplet and paper microfluidic technique that enables rapid (∼70 s), highly efficient (≥98%) blood plasma separation from reduced sample (∼6 μL), alongside automated downstream biomarker detection. Evaporation-driven natural convection enhances fluid mixing within the blood droplet, while capillary-driven plasma extraction ensures selective, high-purity separation without external actuation. Overcoming limitations of conventional μPAD-based blood microsampling, this hybrid strategy delivers high sensitivity, reproducibility, and multiplexing capabilities. It achieves ≥90% analytical accuracy for simultaneous detection of glycemic, albuminic, and diabetic conditions. A custom application (GPS App.) facilitates real-time, automated quantification, ensuring unbiased diagnostics in extreme point-of-care settings. This work establishes a scalable, cost-effective, and highly efficient biosensing platform, integrating multiple passive microfluidic strategies to enhance analytical precision by overcoming limitations of individual systems.