Microfluidic Systems for Isolation of White Blood Cells: From Design to Practical Applications

White blood cells (WBCs) are key immune cells that defend against infections and regulate immunity. For accurate diagnosis, WBCs must be separated from red blood cells (RBCs), which can interfere with analysis. Microfluidic methods provide an efficient solution for high-purity WBC isolation, utilizing miniaturized devices that need minimal blood and enable on-chip disease detection and cell counting, thus enhancing point-of-care accessibility. This review focuses on passive microfluidic techniques, known for their simplicity and scalability, which separate WBCs by leveraging factors like RBC concentration, channel geometry, and flow dynamics. The low WBC-to-RBC ratio (1:1000) remains a major challenge, with few current technologies integrating WBC isolation and disease detection. This work emphasizes the principles and applications of passive separation methods and examines biological assays of isolated WBCs. Additionally, we discuss commercial devices and highlight opportunities for innovation in microfluidic platforms to address existing gaps, particularly in improving diagnostic efficiency and usability. By advancing versatile and user-friendly technologies, microfluidic systems have the potential to revolutionize point-of-care diagnostics and healthcare delivery.