A microfluidic platform for long-term culturing of explanted tissues

A research group of Dr. Yo Tanaka (Group B01, RIKEN) has developed a new system for keeping tissue viable for long-term study once transferred from an animal to a culture medium. The new system uses a microfluidic device that can keep tissue from both drying out and from drowning in fluid. A proof-of-concept experiment showed that tissue explanted from the mouse brain remained viable after almost one month in culture, much longer than is possible with other microfluidic culturing methods, and also much simpler.
Experimenting on tissues in culture can facilitate drug discovery because researchers can systematically manipulate the tissue and test different drugs or drug combinations. However, when studying a whole system in which many cells must interact with each other, it has proven difficult to keep the tissue “alive” for more than a few days. Tissue dries out quickly and dies unless it is put into a wet culture medium with appropriate nutrients. On the other hand, immersing complex tissue in fluid can damage the tissue because it does not allow the normal transfer of gases between them.
To solve this problem, the team developed a microfluidic device using polydimethylsiloxane (PDMS), the material often used as a defoamer in over-the-counter drugs. The device has a semi-permeable channel surrounded by an artificial membrane and solid PDMS walls. Rather than constantly being immersed in fluid, the tissue benefited from having the culture medium circulate within the microchannel and pass through the permeable membrane, which allowed proper gas exchange. This sounds simple, but finding the optimal settings proved challenging.
The team tested the device using tissue from the mouse suprachiasmatic nucleus, a complex part of the brain that governs circadian rhythms. The mice themselves were knock-in mice in which circadian rhythm activity in the brain was linked to the production of a highly fluorescent protein. By measuring the level of bioluminescence coming from the brain tissue, they were able to see that tissue kept alive by their system stayed active and functional for over 25 days with nice circadian activity. In contrast, neural activity in tissue kept in a conventional culture decreased by 6% after only 10 hours.
This new method will be useful in this soft robotics field by providing a technique for long-term tissue culture and measurement of circadian rhythms carried out in this field.
The study was published in Analytical Sciences on October 10th.

Paper title: A Microfluidic Platform Based on Robust Gas and Liquid Exchange for Long-Term Culturing of Explanted Tissues
Link to the paper: https://doi.org/10.2116/analsci.19P099