Advances in Whole Blood Separation Techniques for Point-of-Care Testing

Despite its ubiquity as a clinical sample, whole blood remains inherently challenging to use in diagnostics, leading to routine reliance on serum and plasma in clinical testing. Whole blood is a complex mixture of cells, lipids, proteins, and metabolites, many of which can interfere with assays designed for plasma or serum if used directly, thereby reducing the sensitivity and accuracy. While traditional laboratory workflows use multistep preparations and benchtop instruments such as centrifuges to overcome these challenges, such methods are often impractical for point-of-care applications, particularly in decentralized or resource-limited settings. This review systematically examines whole blood-based point-of-care testing (POCT) platforms that either operate directly on blood samples or integrate current or emerging separation techniques, including centrifugation, microfluidics, membrane filtration, capillary-driven flow, electrophoresis, and acoustofluidics. We highlight the operational principles, performance metrics (yield, purity, turnaround time), and feasibility of these approaches for a reliable integrated POCT deployment. By evaluating these technologies against the functional demands of modern diagnostics, we outline trade-offs among efficiency, cost, complexity, and integration potential. Our goal is to provide a framework for selecting or engineering appropriate blood separation strategies tailored to specific diagnostic needs, ultimately supporting the broader deployment of POCT across community clinics, emergency medicine, and at-home settings.