Design advances in pinched flow fractionation for enhanced particle separation in microfluidics

, modifications to the pinched and broadened segments increase separation distance, microvalve-integrated outlets enable real-time control, active method integration improves separation resolution, and inertial microfluidic hybridization enhances throughput. Besides, we review representative applications of PFF, like the separation of extracellular vesicles for immunoblotting and microplastics for water quality evaluation. Design guidelines promoting the separation performance are discussed, alongside potential biological particle targets and a comparative analysis of PFF and other separation techniques. Finally, future directions are proposed, emphasizing the integration of passive methods and device parallelization to maintain PFF's simplicity while improving throughput and separation capabilities. This review aims to provide theoretical insights and technical guidance for continuous innovation in PFF, promoting its practical implementation across biomedical and environmental monitoring fields.