The culture of mouse embryos ex utero and continuous monitoring and imaging of embryos as they develop have applications in drug testing, genetic studies, and basic research on embryonic development. However, the embryo culture systems currently available for post-implantation embryos include rolling bottle culture systems, which do not permit imaging of the developing embryos and do not support the long-term survival and development of embryos ex utero. Current culture systems for pre-implantation stage embryos, including microfluidic culture systems, are suitable for short-term culture of very early stage embryos – such as fertilized zygotes. However, they are not suitable for the culture and survival of post-implantation stage embryos. Similarly, the cell culture systems currently available (e.g., slides, multi-well plates, and microfluidic chambers) may allow for imaging of single-dimensional structures such as cells, but cannot be used for culturing or imaging three-dimensional structures such as embryos. Therefore, there is a need for a system that provides long-term embryo culturing combined with imaging. Such a system could support long-term culture while allowing for continuous imaging of the developing embryos.
Scientists at the National Eye Institute (NEI) have developed an embryo culture chamber, an embryo culturing and imaging system, and a method of culturing and imaging an embryo. The chamber allows for the continuous imaging of the embryo for the culture period. This invention is available for licensing and co-development.
Figure: Mouse embryo culture imaging multi-chamber system. The multi-chamber mouse embryo culture imaging system consists of multiple embryo culture chambers connected to a common medium and gas (95% O2/5% CO2) source. Culture medium (and serum/blood) flows through the peristaltic pump into the culture chamber (blood/serum flows through internal sub-chamber) submerging the embryos and passes through the outlets to recirculate. Gas flow through the chambers can be monitored as it passes through the water trap and adjusted by a flow meter. The inlet shows enlarged view of the culture chamber with a microscope objective lens for imaging and a removable chamber lid. Mouse embryos are cultured on specialized platform with pores and elevations to provide minimal contact with the surface and allow free flow of medium in all directions. The serum/blood flowing through the internal sub-chamber baths the mouse placenta/yolk sac simulating placental blood supply.