Novel method automates the growth of brain tissue organoids on a chip: The new system can increase reproducibility in cerebral organoid research and shows promise for lowering levels of cellular stress

A team of engineers at UC Santa Cruz has developed a new method for remote automation of the growth of cerebral organoids — miniature, three-dimensional models of brain tissue grown from stem cells. Cerebral organoids allow researchers to study and engineer key functions of the human brain with a level of accuracy not possible with other models. This has implications for understanding brain development and the effects of pharmaceutical drugs for treating cancer or other diseases.

In a new study published in the journal Nature Scientific Reports, researchers from the UCSC Braingeneers group detail their automated, internet-connected microfluidics system, called “Autoculture.” The system precisely delivers feeding liquid to individual cerebral organoids in order to optimize their growth without the need for human interference with the tissue culture.

Cerebral organoids require a high level of expertise and consistency to maintain the precise conditions for cell growth over weeks or months. Using an automated system, as demonstrated in this study, can eliminate disturbance to cell culture growth caused by human interference or error, provide more robust results, and allow more scientists access to opportunities to conduct research with human brain models.

Autoculture also addresses variation that arises in organoid growth due to “batch effect” issues, where organoids grown at different times or at different labs under similar conditions may vary just because of the complexity of their growth. Using this uniform, automated system can reduce variation and allow researchers to better compare and validate their results.

“One of the big challenges is that these cultures are not very reproducible, and in part it’s not surprising because these are months-long experiments. You have to change media every couple of days and try to treat these cultures uniformly, which is extremely challenging,” said Sofie Salama, an acting professor of molecular, cellular and developmental biology at UCSC and an author on the study.

Unique design

Autoculture uses a microfluidic chip designed by the researchers, spearheaded by Associate Professor of Electrical and Computer Engineering Mircea Teodorescu and Biomolecular Engineering Ph.D. student Spencer Seiler. Their novel chips, created from a unique bi-layer mold, have tiny wells and channels for delivering minute amounts of liquid to the organoid, which allow the scientists to have a high level of control over nutrient concentrations and byproducts. Overall, the system uses mostly off-the-shelf, low-cost components, making it accessible and modular.

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