Development of a fully-automated, high-throughput 3D iPSC lineage-differentiation platform

Bioengineers from the Helmholtz Pioneer Campus implement a microfluidic large-scale chip platform for automated 3D iPSC lineage-differentiation and high-throughput imaging.

Even though a number of microfluidic platforms for the integration of 3D cell cultures have been designed, fully automated higher-throughput versions for combined 3D iPSC (induced pluripotent stem cell) lineage differentiation and analysis are still rare, particularly for human iPSCs. While the microfluidic large-scale integration (mLSI) chip technology has set standards for automated 2D cell culture systems, its extension to 3D is challenging because of the relatively large size of the developing cell clusters. In addition, general operation units and elements for forming and handling 3D cultures are missing and the increasing demand for the system’s compatibility with high-content imaging and other analytical workflows is not covered.
Now, the team of Matthias Meier from the Helmholtz Pioneer Campus reports on a new, fully automated platform that not only lives up to the standards of current state-of-the-art microfluidic systems, but, by the addition of u-shaped pneumatic valves, is also able to trap cells and keep the developing clusters within a controlled size while maintaining their 3D architecture and homogeneity. On top, the system comes with the option of retrieving the cell aggregates for further analysis outside of the platform (FACS, IF, etc).
The team demonstrated the benefit of this technical advancement by assessing and optimizing stem cell differentiation protocols in order to (a) reduce the number of off-target cells associated with long-term cultivation of iPSC, (b) gain more functional mature cell types and (c) increase the yield. This is a major step forward towards a better understanding of the chemical, temporal, and spatial microenvironment of the in vivo counterparts of the target organ (in the present study: the pancreas), which is key for rebuilding organotypic tissues in vitro.
Taken together, the technical advancements now enable broad experimental applications with high reproducibility and with the general analytical workflow in place, allow for optimal in vitro generation of various cell types for future cell replacement therapies. 

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