A Paper-Droplet Hybrid System for Efficient Blood Plasma Separation in Multiplex Diagnostics

Single PAD-based lateral flow blood plasma separation techniques suffer from low sensitivity, inconsistent performance, and extended turnaround times, hindering point- of-care whole blood multiplexing. Integrating multifunctional microfluidic approach could offer a paradigm shift, providing rapid, high-throughput blood testing with reduced sample alongside streamlined downstream automation. Herein we report a novel low-cost sessile-drop and paper hybrid blood plasma separation technique that achieves efficient ([≥] 98 %) separation within seconds ([~]70 s). Evaporation-driven natural convection within a sessile blood droplet facilitates effective mixing, while capillary forces prevalent in the paper structure selectively transport plasma to the detection zones, all without any externally applied motive force. The separated plasma is successfully analysed for simultaneous glucose and albumin detection using colorimetric assay. This method demonstrates high accuracy in predicting glucose and albumin levels in healthy and diseased samples when benchmarked against an Automated Biochemistry Analyzer. A 3D foldable all-in-one paper microfluidic device, complemented by a MATLAB based application (GPS App.) has been developed for quantitative assessment during on-field diagnostics. This study presents a rapid, efficient, and user-friendly alternative to traditional flow-based separation, providing reliable detection in resource-limited settings.