Sperm Syringe: 3D Sorting Platform for Assisted Reproduction

Abstract

sperm injection (ICSI), [3] in vitro fertilization (IVF), [4] and intrauterine insemination (IUI). [5] In ICSI, as the most invasive method, an individual sperm is selected and injected directly into an egg. In IVF or IUI, a subpopulation of pre-selected sperm is introduced close to the egg to achieve fertilization. [3][4][5] The quality of selected sperm is crucial to ART, contributing significantly to the treatment success rate, live-birth rate, and offspring health. [6] However, the current clinical sperm selection practices are highly manual, subjective, and prone to operator errors, resulting in a suboptimal ART success rate, stagnating at ≈33% per cycle over the past 30 years. [7,8] The inherent challenge is to mimic the highly parallelized and 3D selection process in vivo that enables a single-cell level sorting mechanism within a relatively short timeframe. [9] Specifically, the 3D folded structure of the female reproductive tract breaks down the initial semen volume (≈1-4 mL) into a few microliters per selection event within the folded epithelial of the fallopian tube. These subfractioning events can process hundreds of millions of sperm in just a few hours. [10] Current clinical practices, however, only provide a 2D bulk scale selection alternative.Density gradient centrifugation (DGC) [11] and swim-up [12,13] are the most commonly used methods for human sperm selection in fertility clinics. In swim-up assay (SU), highly motile sperm are selected based on their ability to swim upward from the raw semen sediment into a fresh sperm media, where they are collected after ≈60 min. This method is not applicable in the case of asthenozoospermia (poor sperm motility). [14] In DGC, human sperm are separated based on their density by being forced to cross a viscosity gradient via centrifugation force that could cause sperm DNA damage and alter sperm morphology and function. [11,15] The sperm preparation method that is used in clinics is mainly chosen based on the count and motility of sperm in the human semen sample. [9] Both SU and DGC are time consuming (30-60 min), require multiple preparation steps, depend on the clinician expertise, and differ significantly from the natural selection process in vivo. [16] Moreover, the relatively long processing time of these methods and the low percentage of recovered sperm in the swim-up method (less than 20%) have considerably restricted the clinical workflow, especially Selection of high-quality sperm is crucial to assisted reproduction. However, conventional clinical methods for sperm selection are manual and prone to operator errors. This article presents 'sperm syringe', a scalable technology that mimics the highly parallelized 3D selection process in vivo via a 3D network of 560 microchannels to select high-quality sperm. Sperm syringe retrieves more than 41% of healthy sperm from the initial sperm sample in under 15 min, providing a sufficient volume (≈500 µL) and number (1,600,000) of high-quality sperm for fertility treatments. Experiments with bull and human sper...

Sperm quality metrics were improved by a biomimetic microfluidic selection platform compared to swim-up methods

“…However, due to the global popularity of DGC and its functionally different selection mechanism, further comparative testing against DGC, SU, and DGC plus SU combinations will be necessary for clinical adoption. Microfluidics has been increasingly involved in ART studies, and several devices have been explored to sort motile or morphologically intact sperm from unprocessed semen 33,[42][43][44][45][46][47] . However, the translation of these technologies into clinics has been extremely limited, largely due to their complexity in operation, instability, and/or inconsistency, which often result from mechanisms such as gravity pumps, laminar flow, or charge-based selection.…”

Lab on a chip devices for fertility: from proof-of-concept to clinical impact

“…1a and b, Table 1). To help with clinical implementation, these approaches were further improved with respect to manufacturing technique (switching from soft-lithography to methods that are better suited to mass production), device material (using materials other than PDMS that are clinically acceptable), operational procedure and/or throughput, 22–24 providing selection methods than can offer automation, reduce clinician time and outperform conventional practices (Fig. 1c and d).…”

Selecting active matter according to motility in an acoustofluidic setup: self-propelled particles and sperm cells

“…A passively driven self-contained integrated microfluidic device for separation of motile sperm has been presented 2 that isolates motile sperm based on its ability to cross streamlines in a laminar fluid stream. [2][3][4] Similarly, a variety of sperm-selecting devices have been proposed, including a rather sophisticated ''sperm syringe'' 5 and other devices, 6 employing the same passive selection principle as the early works. [2][3][4]7 In an attempt to model the environment in the bovine reproductive tract, where sperm is guided through the cervix by entering microgrooves in the walls of the endocervical canal, a device was proposed modeling the grooves of the cervix 8 allowing separation of motile from immotile bull sperm.…”