Passive Blood-Plasma Separation via Constriction-Expansion Geometry in Untreated Paper Microfluidic Devices

Efficient plasma separation from whole blood is an essential preprocessing step in clinical diagnostics, as plasma is preferred for most colorimetric and biochemical tests over whole blood. Traditional separation methods, such as centrifugation, need laboratory facilities and trained personnel, making them unsuitable for point-of-care (POC) diagnostics. Although paper-based microfluidic devices emerged as a promising solution to the above limitations, most existing paper-based devices rely on filtration membranes, chemical functionalization, or both, increasing device complexity and cost. In the present study, membrane- and reagent-free paper-based microfluidic devices have been designed and developed that achieve blood-plasma separation solely through geometric control of the wicking pathway, eliminating the requirement of any external separation aids. Two devices were designed and fabricated embedding constriction-expansion flow path, with and without a localized hydrophobic barrier, to selectively trap red blood cells while allowing plasma to wick through the porous cellulose network. Experimental results demonstrate consistent plasma separation, with a maximum plasma separation efficiency of ∼64% for the optimized design. Further, to elucidate the underlying mechanism, an analytical formulation for capillary transport considering non-Newtonian blood rheology coupled with two-phase numerical simulations was developed. Finally, the reliability of the proposed devices was further validated through protein (albumin) analysis of the separated plasma, which closely matched the clinical laboratory measurements. The present work establishes a simple, low-cost, equipment- and chemical-free strategy for effective blood-plasma separation achieved solely through structural design, while preserving analyte integrity, offering a viable solution for POC diagnostic applications.