Microfluidic sperm selection for assisted reproduction: Biomimetic strategies, clinical translation, and future perspectives

The identification and selection of physiologically competent sperm is vital in assisted reproductive techniques. Existing methods of sperm preparation such as swim-up and density-gradient centrifugation enrich sperm according to their motility and density; however, they do not capture the diverse physiological cues involved in sperm selection in vivo. Reproductive biology has identified several mechanisms governing sperm navigation and selection, such as rheotaxis, chemotaxis, thermotaxis, boundary-following behavior, and migration through a viscoelastic environment. These concepts inspired the development of microfluidic platforms that provide a minimally invasive environment for sperm selection. This review aims to examine how physiologically relevant sperm-selection principles are translated into microfluidic strategies and to critically evaluate their biological fidelity, functional validation, clinical relevance, and potential for precision sperm selection. We examine the biological basis of sperm selection and its translation into microfluidic systems, compare these approaches with conventional and functional sperm-selection methods, and evaluate outcomes beyond conventional semen parameters, applications in challenging male infertility phenotypes, commercial and clinical translation, and AI-assisted sperm assessment and recovery. Particular emphasis is placed on distinguishing biomimetic design from demonstrated biological and clinical benefit. Although remarkable advances have been made, many difficulties remain in standardization, biological and reproductive validation, phenotype specificity, AI integration, and clinical implementation of these techniques. Further development should focus on a nature-inspired rather than a-replicating approach with standardized validation and phenotype specificity.