Making immotile sperm motile using high-frequency ultrasound.

Sperm motility is a natural selection with a crucial role in both natural and assisted reproduction. Common methods for increasing sperm motility are by using chemicals that cause embryotoxicity, and the multistep washing requirements of these methods lead to sperm DNA damage. We propose a rapid and noninvasive mechanotherapy approach for increasing the motility of human sperm cells by using ultrasound operating at 800 mW and 40 MHz. Single-cell analysis of sperm cells, facilitated by droplet microfluidics, shows that exposure to ultrasound leads to up to 266% boost to motility parameters of relatively immotile sperm, and as a result, 72% of these immotile sperm are graded as progressive after exposure, with a swimming velocity greater than 5 micrometer per second. These promising results offer a rapid and noninvasive clinical method for improving the motility of sperm cells in the most challenging assisted reproduction cases to replace intracytoplasmic sperm injection (ICSI) with less invasive treatments and to improve assisted reproduction outcomes.

Curvature in the reproductive tract alters sperm-surface interactions.

The fallopian tube is lined with a highly complex folded epithelium surrounding a lumen that progressively narrows. To study the influence of this labyrinthine complexity on sperm behavior, we use droplet microfluidics to create soft curved interfaces over a range of curvatures corresponding to the in vivo environment. We reveal a dynamic response mechanism in sperm, switching from a progressive surface-aligned motility mode at low curvatures (larger droplets), to an aggressive surface-attacking mode at high curvatures (smaller droplets of <50 µm-radius). We show that sperm in the attacking mode swim ~33% slower, spend 1.66-fold longer at the interface and have a 66% lower beating amplitude than in the progressive mode. These findings demonstrate that surface curvature within the fallopian tube alters sperm motion from a faster surface aligned locomotion in distal regions to a prolonged physical contact with the epithelium near the site of fertilization, the latter being known to promote capacitation and fertilization competence.

Microfluidic Valves for Selective on-Chip Droplet Splitting at Multiple Sites.

We describe a microfluidic system for control of droplet division at two locations using a T-junction and expansion channel which are placed one after another. Droplets generated at a standard T-junction are introduced into the droplet division section of the microchannel. In the first set of experiments, the droplet division section consists of two consecutive identical T-junctions branching from the main channel. With this geometry, we were able to produce daughter droplets only at the first junction while there was no droplet division at the second junction. Resistive network analysis is used to redesign the microchannel geometry with an expansion channel in place of the second junction, to have the same quantity of flow entering in both the junctions. We observed five different regimes of droplet breakup, namely, (1) no droplet breakup in both junctions, (2) droplet breakup in the first junction, (3) droplet breakup in both junctions with higher daughter droplet volume in the first junction, (4) daughter droplet volume higher in the second junction, and (5) intermittent droplet breakup in both the junctions. Under specific flow conditions, droplet interaction with both the junctions is similar. We then showed design requirements for location of microvalves, simulated by deformation of the main channel wall and by experiments to break the droplet.