Development of a novel cervix-inspired tortuous microfluidic system for efficient, high-quality sperm selection.

Microfluidic systems have been extensively studied in recent years as potential alternatives for problematic conventional methods of sperm selection. However, despite the widespread use of simple straight channels in these systems, the impact of channel geometry on selected sperm quality has not been thoroughly investigated. To explore this further, we designed and fabricated serpentine microchannels with different radii of curvature, inspired by the tortuous structure of the cervix. Our results showed that in the presence of gentle backflow, microfluidic channels with a 150 µm radius of curvature significantly enhanced the quality of selected sperms when compared to straight channels. Specifically, we observed significant improvements of 7% and 9% in total motility and progressive motility, respectively, as well as 13%, 18%, and 19% improvements in VCL, VAP, and VSL, respectively. Through careful observation of the process, we discovered a unique near-wall sperm migration pattern named boundary detachment-reattachment (BDR), that was observed exclusively in curved microchannels. This pattern, which is a direct consequence of the special serpentine geometry and sperm boundary-following characteristic, contributed to the superior selection performance when combined with a fluid backflow. After determining the best channel design, we fabricated a parallelized chip consisting of 85 microchannels capable of processing 0.5 ml of raw semen within 20 minutes. This chip outperformed conventional methods of swim-up and density gradient centrifugation (DGC) in terms of motility (9% and 25% improvements, respectively), reactive oxygen species (18% and 15% improvements, respectively), and DNA fragmentation index (14% improvement to DGC). Outstanding performance and advantages such as user-friendliness, rapid selection, and independence from centrifugation make our microfluidic system a prospective sperm selection tool in clinical applications.

Enrichment of bovine milk-derived extracellular vesicles using surface-functionalized cellulose nanofibers.

The isolation of extracellular vesicles (EVs) from milk, a complex mixture of colloidal structures having a comparable size to EVs, is challenging. Although ultracentrifugation (UC) has been widely used for EV isolation, this has significant limitations, including a long processing time at high g-force conditions and large sample volume requirements. We introduced a new approach based on nature nanoentities cellulose nanofibers (CNFs) and short time and low g-force centrifugation to isolate EVs from various milk fractions. The flexible and entangled network of CNFs forms nanoporous, which entraps the EVs. Further, positively charged CNFs interact with anionic EVs through an electrostatic attraction, promoting their isolation with efficiency comparable with UC. The functionality and toxicity of isolated milk EVs were tested in Caco2 cells. Overall, the newly developed approach provides straightforward isolation and biocompatibility and preserves the natural properties of the isolated EVs, enabling further applications.

Effects of cone angle and length of nanopores on the resistive pulse quality.

Resistive pulse sensing (RPS) has proved to be a viable method for the detection and characterization of micro and nano particles. Modern fabrication methods have introduced different nanopore geometries for resistive pulse sensors. In this paper, we have numerically studied the effects of membrane thickness and the pore's cone angle, as the main geometrical parameters, on the sensing performance of the nanopores used for nanoparticle detection in the resistive pulse sensing method. To compare the sensing performance, three resistive pulse quality parameters were investigated - sensitivity, pulse duration and pulse amplitude. The thorough investigation on the relations between the geometrical parameters and the pulse quality parameters produced several interesting results, which were categorized and summarized for different nanopore structures (as different nanopore platforms) enabling the readers to more effectively compare them with one another. The results revealed that large cone angle and low aspect ratio nanopores have higher pulse amplitude and sensitivity, but their low duration could be a challenge in the process of detecting the resistive pulse. In addition, our results show small variation in sensitivity and duration of large cone angle nanopores with respect to pore length change, which is explained using the effective length concept and the definition of electric field strength and length. The findings of the present work can be used in practical applications where choosing the optimal pore geometry is of crucial significance. Furthermore, the results provide several possible ways to improve the resistive pulse quality for better sensing performance.