Application of microfluidic technologies to human assisted reproduction

Abstract

Microfluidics can be considered both a science and a technology. It is defined as the study of fluid behavior at a sub-microliter level and the investigation into its application to cell biology, chemistry, genetics, molecular biology and medicine. There are at least two characteristics of microfluidics, mechanical and biochemical, which can be influential in the field of mammalian gamete and preimplantation embryo biology. These microfluidic characteristics can assist in basic biological studies on sperm, oocyte and preimplantation embryo structure, function and environment. The mechanical and biochemical characteristics of microfluidics may also have practical and/or technical application(s) to assisted reproductive technologies (ART) in rodents, domestic species, endangered species and humans. This review will consider data in mammals, and when available humans, addressing the potential application(s) of microfluidics to assisted reproduction. There are numerous sequential steps in the clinical assisted reproductive laboratory process that work, yet could be improved. Cause and effect relations of procedural inefficiencies can be difficult to identify and/or remedy. Data will be presented that consider microfluidic applications to sperm isolation, oocyte cumulus complex isolation, oocyte denuding, oocyte mechanical manipulation, conventional insemination, intracytoplasmic sperm injection, embryo culture, embryo analysis and oocyte and embryo cryopreservation. While these studies have progressed in animal models, data with human gametes and embryos are significantly lacking. These data from clinical trials are requisite for making future evidence-based decisions regarding the application of microfluidics in human ART.

Rheotaxis-based separation of sperm with progressive motility using a microfluidic corral system

“…In the past decade, some microfluidic devices have been proposed for ART applications (27)(28)(29), including those that have been used to separate sperm (30). In one effort, a passive microfluidic system called microscale integrated sperm sorter (MISS) was proposed that could separate motile sperm from the rest of the sample (8).…”

Microfluidic technology for in vitro fertilization (IVF)

“…Similar to IVF, ICSI has been the choice of many patients with male infertility [53]. However, while the threat of oocyte lysis while inserting the needle into the oocyte still remains [54], the causes of oocyte degeneration have seldom been investigated [55]. One of the reasons for oocyte degeneration is technician error [56].…”

“…Raty et al demonstrated that mouse embryos cultured in microchannels had a greater number of blastocysts with a lower percentage of degenerated embryos than those with controlled microdrops [100]. However, the retrieval of the cultured embryos from the microchannels remains uncertain [54]. In 2004, Gu et al developed a microfluidic device with computer programming to regulate the fluid flow in the microchannel [101].…”

Clinical Application of In Vitro Maturation of Oocytes

“…The three-dimensional culture system can support the development of follicles by using biological materials to maintain cell-to-cell information exchange. In addition, mature oocytes can be obtained by using a three-dimensional culture system in the in vitro culture of anterior follicles of nonhuman primates [35], although no reports are available regarding the use of a three-dimensional culture system in the in vitro culture of immature human oocytes. A past study has used microreactors to form three-dimensional bioreactors to support the growth of different types of cells [36].…”