Rapid selection of sperm with high DNA integrity

Abstract

Sperm selection is essential to assisted reproductive technology (ART), influencing treatment outcomes and the health of offspring. The fundamental challenge of sperm selection is dictated by biology: a heterogeneous population of ~10(8) sperm per milliliter with a short lifetime in vitro. However, conventional sperm selection approaches result in less than 50% improvement in DNA integrity. Here, a clinically applicable microfluidic device is presented that selects sperm based on the progressive motility in 500 parallel microchannels. The result is a one-step procedure for semen purification and high DNA integrity sperm selection from 1 mL of raw semen in under 20 minutes. Experiments with bull sperm indicate more than 89% improvement in selected sperm vitality. Clinical tests with human sperm show more than 80% improvement in human DNA integrity, significantly outperforming the best current practices. These results demonstrate the presence of a sub-population of sperm with nearly intact chromatin and DNA integrity, and a simple clinically-applicable lab-on-a-chip method to select this population.

Recent advances in microfluidic diagnostic and treatment systems for assisted reproductive technologies in developing countries

“…In sections 4.4. and 4.5., we summarized evidence that sorted motile sperm possess higher DNA integrity, as indicated by studies of microfluidic devices without centrifugation [57,58,62,63,85]. Developments and applications of microfluidics have contributed markedly to improvements in ART over the past 20 years.…”

“…Relationships between DNA fragmentation and fertility have been discussed previously [82,84], and in a previous meta-analysis by Osman et al, significant increases in live birth rates were observed after fertilization with sperm that had lower DNA fragmentation rates [82]. Moreover, using silicone microfluidic channels, motile sperm with high DNA integrity were selected toward a central outlet based on progressive motility in 500 parallel microchannels with cross--section dimensions of 100 × 75 μm [85]. In 2016, Nosrati et al reported a novel analytical system for assessing DNA integrity using ion concentration polarization on paper and applying voltage (150 V) to the sample channel on the paper [86].…”

Application of microfluidic technologies to human assisted reproduction

“…Normal human semen volumes are typically greater than 1.5 ml, with 50% of samples greater than 3.7 ml (WHO, 2010). Recently, a clinically applicable microfluidic device was described that isolates sperm based on the progressive motility in 500 parallel microchannels and represents a one-step procedure for sperm selection with high motility and high DNA integrity sperm (Nosrati et al, 2014) (Fig. 1).…”

Micro- and nanofluidic systems in devices for biological, medical and environmental research

“…A number of new portable microfluidic devices were reported [9] with many built-in functions for creating simpler ones [10], faster and cheaper devices [11] with better detection limits. Microfluidic device consisting of 500 channels is intended for the rapid analysis (within 20 minutes) of the integrity of the sperm DNA using fluorescent imaging [11]. In experiments a significant increase in the viability of the bull and human sperm was demonstrated in comparison with existing methods.…”