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Variations in oxygen levels play key roles in numerous physiological and pathological processes, but are often not properly controlled in in vitro models, introducing a significant bias in experimental outcomes. Recent developments in microfluidic technology have introduced a paradigm shift by providing new opportunities to better mimic physiological and pathological conditions, which is achieved by both regulating and monitoring oxygen levels at the micrometre scale in miniaturized devices. In this review, we first introduce the nature and relevance of oxygen-dependent pathways in both physiological and pathological contexts. Subsequently, we discuss strategies to control oxygen in microfluidic devices, distinguishing between engineering approaches that operate at the device level during its fabrication and chemical approaches that involve the active perfusion of fluids oxygenated at a precise level or supplemented with oxygen-producing or oxygen-scavenging materials. In addition, we discuss readout approaches for monitoring oxygen levels at the cellular and tissue levels, focusing on electrochemical and optical detection schemes for high-resolution measurements directly on-chip. An overview of different applications in which microfluidic devices have been utilized to answer biological research questions is then provided. In the final section, we provide our vision for further technological refinements of oxygen-controlling devices and discuss how these devices can be employed to generate new fundamental insights regarding key scientific problems that call for emulating oxygen levels as encountered in vivo. We conclude by making the case that ultimately emulating physiological or pathological oxygen levels should become a standard feature in all in vitro cell, tissue, and organ models. [ABSTRACT FROM AUTHOR]

Microfluidics, which is the science to manipulate fluids at the micrometer scale, was initially introduced to create lab-on-a-chip devices, for analytical purposes. Since then, microfluidics has significantly spread out to other fields of applications to also give rise to other sub-domains, like that of organs-on-chip. In this review, we first introduce microfluidics and organ-on-chip technologies, and summarize advantages presented by these miniaturized devices for life sciences and health applications. After a short overview of some of key-applications in these fields, we discuss opportunities possibly offered by microfluidic devices and organon-chip models for reproductive medicine and biology. Following this, we review various microfluidic devices developed for gamete analysis and sorting, for performing one or multiple steps of an IVF cycle, or for modeling reproductive organs and tissues, either for embryo production and growth in a biomimetic environment, or for reprotox applications. We conclude with a critical discussion on where these technologies of microfluidics and organ-on-a-chip currently stand, and on some of the remaining challenges before these devices could be adopted in clinical routines. [ABSTRACT FROM AUTHOR]