Microfluidic technology: new opportunities to develop physiologically relevant in vitro models - Integrated microfluidic platform for the in vitro pre-implantation culture of individual mammalian embryos and their in situ characterization

摘要

Here, we report the development of an integrated sensing platform for the field of assisted reproductive technologies (ART), and more specifically for the pre-implantation culture of mammalian embryos and their in situ characterization through evaluation of their metabolic activity. The entire platform consists of a nanoliter-culture chamber, with an integrated oxygen sensor to monitor the respiratory activity of individual embryos, as a marker for their viability and developmental competence. We first discuss the key-advantages of microfluidic technology to realize such an integrated sensing platform. We next present the culture device, and its validation on mouse embryos. This first stage validation reveals that microfluidics supports the full-term development of mouse embryos down to the single embryo level with birth rates comparable to group culture in conventional formats. In a second step, the device is upgraded for the culture of human embryos, and tested on donated frozen-thawed embryos. Finally, we describe an oxygen sensor consisting of an ultra-microelectrode array (UMEA) to be integrated in the culture device. Using this UME-based sensor, we also propose a novel measurement approach at short timescales, which allows reducing drastically the amount of oxygen consumed through the electrochemical measurements. Current work focuses on the integration of the sensor in the culture platform and its validation on biological materials. The integrated platform is currently tested on spheroids, which are used as surrogates of mammalian embryos, before it is applied on mouse embryos.