Abstract

Microfluidic Sorting of Sperm For Applications in Assisted Reproductive Technologies

Utkan Demirci, Professor, Stanford University School of Medicine

Micro- and nano-scale technologies can have a significant impact on medicine and biology in the areas of cell manipulation, diagnostics and monitoring. At the convergence of these new technologies and biology, we research for enabling solutions to real-world problems at the clinic. Emerging nano-scale and microfluidic technologies integrated with biology offer innovative possibilities for creating intelligent, mobile medical lab-chip devices that could transform diagnostics and monitoring, tissue engineering and regenerative medicine. Male infertility is a reproductive disease, and existing clinical solutions for this condition often involve long and cumbersome sperm sorting methods, including preprocessing and centrifugation-based steps. These methods also fall short when sorting for sperm free of reactive oxygen species, DNA damage, and epigenetic aberrations. Existing platforms suffer from structural complexities, i.e., pumps or chemoattractants, setting insurmountable barriers to clinical adoption. Inspired by the natural filter-like capabilities of the female reproductive tract for sperm selection, a model-driven design—featuring pillar arrays that efficiently and noninvasively isolate highly-motile and morphologically normal sperm, with lower epigenetic global methylation, from raw semen—is presented. The microfluidic sperm sorters that we created, such as the Simple Periodic ARray for Trapping And isolatioN (SPARTAN), modulate the directional persistence of sperm, increasing the spatial separation between progressive and non-progressive motile sperm populations. They lead to results within an unprecedentedly short 10-minute assay time. With over 99% motility of sorted sperm, a 5-fold improvement in morphology, 3-fold increase in nuclear maturity, and 2–4-fold enhancement in DNA integrity, SPARTAN offers to standardize sperm selection while eliminating operator-to-operator variations, centrifugation, and flow. Some of these  innovative microfluidic devices have been translated into FDA approved and CE-marked products, where they have been widely used by fertility clinics around the world to serve patients, leading to an estimated 10,000+ live births globally.