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Embryo development in dynamic microfluidic systems

Profile image of Matteo AgostiniMatteo Agostini
https://doi.org/10.1016/J.SNB.2017.04.186
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8 pages

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Abstract

Infertility has become a highly-spread disease but the efficiency of standard in vitro fertilization (IVF) cycles is only 30%, and their cost is very high. Recently, strategies based on microfluidics and dynamic in vitro systems have been proposed to improve the throughput of successful assisted hatchings. Here, these novel methods are presented and categorized in three main groups: microdroplet dynamic biore-actors, microchannel based cultures and microcontainers. In contraposition to the conventional static cultures, these devices introduce a dynamic microenvironment in order to mimic the physiological dynamic stimulations that are crucial for embryo development. The critical parameters-such as embryo density, medium flow rate, shear stress and microvibration frequency-are discussed and critically compared among the different systems, highlighting their strengths, drawbacks and potential impact on IVF.

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Maryam Kazemi

Advanced Biosystems, 2018

vitro fertilization (IVF), and intrauterine insemination (IUI) provide an excellent opportunity for infertile couples to have their own children. Once considered as a science fiction, IVF and intracytoplasmic sperm injection (ICSI) are now routinely used in fertility clinics. ART is not necessarily only for biologically infertile couples but also for induced infertility. ART techniques such as cryopreservation of gamete/embryo can be used before undergoing treatments such as chemotherapy, which may adversely affect the fertility. ART also has a significant impact on livestock industry, [1] animal husbandry, [2] and world food production. [3] The field has been progressed rapidly in the past 40 years since its inception. Combining ART with tissue engineering and regenerative medicine can lead to the development of artificial uterus, stem cell-derived gametes, and even human cloning. Despite these advances, common ART techniques such as IVF and ICSI still suffer from a variety of limitations. First, as the name of the technology implies, i.e., ART needs to be performed by highly skilled personnel, and the outcome may vary from one expert to another. Second, the whole procedure is still invasive and may potentially cause some complications such as ovarian hyperstimulation syndrome and others. [4] Most importantly, IVF/ICSI bypasses natural selection and in vivo reproductive tract environment. There has been an outstanding improvement in culture medium for gamete handling and sequential replacement of culture media based on embryo needs, mimicking in vivo conditions. However, current physical tools and environment of IVF for gamete manipulation and embryo culture are far from in vivo conditions. In particular, test tubes, Petri dishes, microdroplets, and microwells poorly mimic the dynamic microenvironment, which in vivo embryo experiences during its journey toward the uterus. Such unrealistic conditions not only may affect the quality of the preimplantation embryo and the pregnancy rate but also may influence the epigenetics of the offspring. Immediate effects include low birth weight, high blood pressure, a higher rate of obesity, cardiovascular disease, and increased susceptibility to carcinogens. [5] Future health consequences on the next generation still need to be evaluated in more follow-up studies. Although these complications The fields of assisted reproductive technology (ART) and in vitro fertilization (IVF) have progressed rapidly, yet still need further improvements. Microfluidic technology can incorporate various ART procedures such as embryo/gamete (sperm/oocyte) analysis, sorting, manipulation, culture, and monitoring. The introduction of paper-based and droplet-based microfluidics further improves the commercialization potential of this technology. The progress in 3D printing technology allows for the integration of microfluidics with tissue engineering that may revolutionize current practices in biology and medicine. This review categorizes ART methods according to continuous-flow microfluidics, paperbased microfluidics, droplet-based microfluidics, and organ-on-a-chip. The advances are summarized and potential opportunities in infertility diagnosis, sperm selection, sperm guidance, oocyte selection, insemination, embryo culture, embryo monitoring, and cryopreservation are identified. While some advances of continuous-flow microfluidics for ART have already been reviewed, other microfluidic techniques are still in their early stages. It is envisioned that advances in droplet-based microfluidics, especially digital microfluidics, will allow for more progress in human IVF, particularly single embryo transfer. Droplet-based microfluidics may also lead to fully integrated and high-throughput platforms for animal IVF. Recent advances in organ-on-a-chip including ovary/uterus/oviduct-on-chip platforms hold promise for the integration of the whole human reproductive system-on-a-chip for clinical applications.

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Nano-liter perfusion microfluidic device made entirely by two-photon polymerization for dynamic cell culture with easy cell recovery
Marty Gauvin

Scientific Reports

Polydimethylsiloxane (PDMS) has been the material of choice for microfluidic applications in cell biology for many years, with recent advances encompassing nano-scaffolds and surface modifications to enhance cell-surface interactions at nano-scale. However, PDMS has not previously been amenable to applications which require complex geometries in three dimensions for cell culture device fabrication in the absence of additional components. Further, PDMS microfluidic devices have limited capacity for cell retrieval following culture without severely compromising cell health. This study presents a designed and entirely 3D-printed microfluidic chip (8.8 mm × 8.2 mm × 3.6 mm) using two-photon polymerization (2PP). The ‘nest’ chip is composed of ten channels that deliver sub-microliter volume flowrates (to ~ 600 nL/min per channel) to 10 individual retrievable cell sample ‘cradles’ that interlock with the nest to create the microfluidic device. Computational fluid dynamics modelling predic...

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