Microfluidic shape-based separation for cells and particles: recent progress and future perspective

Shape-based separation of micro- and nanoparticles has emerged as a powerful yet underdeveloped strategy in microfluidics, offering distinct advantages over conventional size-based methods, particularly for biomedical and functional material applications. Unlike size-based separation, shape-based approaches enable discrimination between particles of identical volume but differing morphology, an essential capability for isolating pathological cells, engineered particles, or anisotropic biological entities whose function is inherently linked to shape. This review provides a comprehensive and critical overview of recent progress in both passive and active microfluidic platforms tailored for shape-selective separation. Passive systems such as deterministic lateral displacement, pinched flow fractionation, inertial, and viscoelastic microfluidics exploit hydrodynamic and flow-structure interactions, while active methods including dielectrophoresis, magnetophoresis, optophoresis, and acoustophoresis utilize external fields to modulate particle trajectories based on geometric anisotropy. For example, recent advancements demonstrate high purities often exceeding 95%, with throughput rates ranging from several microliters to milliliters per minute depending on the device configuration, achieving shape-based cell and particle sorting efficiencies above 90% under optimal conditions. For each technique, we highlight the underlying mechanisms enabling shape sensitivity, key technological advancements, and emerging trends in experimental and computational approaches. We also discuss the challenges in capturing complex particle behaviors such as rotation, alignment, and deformability and emphasize the need for integrated modeling, real-time control, and system-level optimization. Finally, we outline future directions and opportunities for advancing shape-based microfluidic separation toward scalable, high-precision applications in diagnostics, therapeutics, and materials science.